US 20120295815A1 ( 19) United States (12 ) Patent Application Publication ( 10 ) Pub . No .: US 2012 /0295815 A1 Lindahl et al. (43 ) Pub . Date : Nov . 22 , 2012 (54 ) DIAGNOSTIC EXPRESSION (30 ) Foreign Application Priority Data PLATFORM Jan . 15, 2010 (GB ) ...... 1000688 . 0 ( 75 ) Inventors : Torbjorn Lindahl, Oslo (NO ); Praveen Sharma, Oslo (NO ) Publication Classification (51 ) Int. CI. ( 73 ) Assignee : DIAGENIC ASA , Oslo (NO ) C40B 40 / 06 (2006 .01 ) C40B 30 / 04 ( 2006 .01 ) (21 ) Appl. No. : 13 /522 , 137 ( 52) U .S . CI...... 506 / 9 ; 506 / 16 (22 ) PCT Filed : Jan . 14 , 2011 ( 57 ) ABSTRACT (86 ) PCT No .: PCT/ EP2011 /050493 The invention provides a set of oligonucleotide probes spe cific to cancer, preferably breast cancer , kits containing them $ 371 (c ) (1 ) , and their use in preparing standard and test patterns and ( 2 ) , ( 4 ) Date : Jul. 13 , 2012 methods of diagnosis of cancer, preferably breast cancer. Patent Application Publication Nov . 22 , 2012 Sheet 1 of 3 US 2012 / 0295815 A1

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DIAGNOSTIC GENE EXPRESSION within a body to provide information relating to the state of PLATFORM the organism from which the cells were derived . WO98 / 49342 describes the analysis of the gene expression of cells distant from the site of disease , e . g . peripheral blood collected [ 0001 ] The present invention relates to oligonucleotide distant from a cancer site . WO04 /046382 , incorporated probes, for use in assessing gene transcript levels in a cell , herein by reference , describes specific probes for the diagno which may be used in analytical techniques, particularly diag sis of breast cancer and Alzheimer 's disease . nostic techniques . Conveniently the probes are provided in kit [0009 ] This finding is based on the premise that the differ form . Different sets of probes may be used in techniques to ent parts of an organism ' s body exist in dynamic interaction prepare gene expression patterns and identify, diagnose or with each other . When a disease affects one part of the body, monitor different cancers , preferably breast cancer, or stages other parts of the body are also affected . The interaction thereof. results from a wide spectrum of biochemical signals that are [0002 ] The identification of quick and easy methods of released from the diseased area , affecting other areas in the sample analysis for, for example , diagnostic applications , body. Although , the nature of the biochemical and physi remains the goal of many researchers. End users seek meth ological changes induced by the released signals can vary in ods which are cost effective , produce statistically significant the different body parts , the changes can be measured at the results and which may be implemented routinely without the level of gene expression and used for diagnostic purposes. need for highly skilled individuals . [0010 ] The physiological state of a cell in an organism is [ 0003 ] The analysis of gene expression within cells has determined by the pattern with which are expressed in been used to provide information on the state of those cells it . The pattern depends upon the internal and externalbiologi and importantly the state of the individual from which the cal stimuli to which said cell is exposed , and any change cells are derived . The relative expression of various genes in either in the extent or in the nature of these stimuli can lead to a cell has been identified as reflecting a particular state within a change in the pattern with which the different genes are a body. For example , cancer cells are known to exhibit altered expressed in the cell . There is a growing understanding that expression of various and the transcripts or the by analysing the systemic changes in gene expression pat expressed proteins may therefore be used as markers of that terns in cells in biological samples , it is possible to provide disease state . information on the type and nature of the biological stimuli [0004 ] Thus biopsy tissuemay be analysed for the presence that are acting on them . Thus, for example , by monitoring the of these markers and cells originating from the site of the expression of a large number of genes in cells in a test sample , disease may be identified in other tissues or fluids of the body it is possible to determine whether their genes are expressed by the presence of the markers . Furthermore , products of the with a pattern characteristic for a particular disease , condition altered expression may be released into the bloodstream and or stage thereof. Measuring changes in gene activities in cells , these products may be analysed . In addition cells which have e . g . from tissue or body fluids is therefore emerging as a contacted disease cells may be affected by their direct contact powerful tool for disease diagnosis . with those cells resulting in altered gene expression and their [ 0011] Such methods have various advantages. Often , expression or products of expression may be similarly analy obtaining clinical samples from certain areas in the body that sed . is diseased can be difficult and may involve undesirable inva [ 0005 ] However, there are some limitations with these sions in the body, for example biopsy is often used to obtain methods. For example , the use of specific tumour markers for samples for cancer . In some cases , such as in Alzheimer ' s identifying cancer suffers from a variety of defects , such as disease the diseased brain specimen can only be obtained lack of specificity or sensitivity , association of the marker post- mortem . Furthermore , the tissue specimens which are with disease states besides the specific type of cancer, and obtained are often heterogeneous and may contain a mixture difficulty of detection in asymptomatic individuals . of both diseased and non - diseased cells , making the analysis [ 0006 ] In addition to the analysis of one or two marker of generated gene expression data both complex and difficult . transcripts or proteins, more recently , gene expression pat [0012 ] It has been suggested that a pool of tumour tissues terns have been analysed . Most of the work involving large that appear to be pathogenetically homogeneous with respect scale gene expression analysis with implications in disease to morphological appearances of the tumour may well be diagnosis has involved clinical samples originating from dis highly heterogeneous at the molecular level (Alizadeh , 2000 , eased tissues or cells . For example , several publications , supra ) , and in fact might contain tumours representing essen which demonstrate that gene expression data can be used to tially different diseases ( Alizadeh , 2000 , supra ; Golub , 1999 , distinguish between similar cancer types, have used clinical supra ). For the purpose of identifying a disease, condition , or samples from diseased tissues or cells ( Alon et al. 1999 , a stage thereof, any method that does not require clinical PNAS , 96 , p 6745 -6750 ; Golub et al. 1999, Science , 286 , p samples to originate directly from diseased tissues or cells is 531 -537 ; Alizadeh et al, 2000 , Nature, 403, p 503 -511 ; Bitt highly desirable since clinical samples representing a homo ner et al ., 2000 , Nature , 406 , p 536 -540 ) . geneous mixture of cell types can be obtained from an easily 0007 ] However, these methodshave relied on analysis of a accessible region in the body. sample containing diseased cells or products of those cells or [0013 ] Cancer of the breast is the most common cancer cells which have been contacted by disease cells . Analysis of among women worldwide with an estimated 1 , 300 , 000 new such samples relies on knowledge of the presence of a disease cases and 465 ,000 deaths annually . To reduce breast cancer and its location , which may be difficult in asymptomatic mortality , early detection and appropriate treatment play a patients . Furthermore , samples can not always be taken from key role . This emphasizes the importance of early detection the disease site , e . g . in diseases of the brain . so that treatment can be initiated as early as possible during [ 0008 ] In a finding of great significance , the present inven tumour development. Mammographic screening , physical tors identified the previously untapped potential of all cells examination and self examination are the main modalities for US 2012 /0295815 A1 Nov . 22 , 2012 breast cancer detection today , but only mammography early after the onset of said cancer , even years before other screening has been shown to reduce mortality . subjective or objective symptoms appear. [0014 ] By the time a tumour is detectable in the breast, [0019 ] As used herein “ systemically " affected genes refers either by palpation or mammography, the tumour may have to genes whose expression is affected in the body without been present for several years and have had the ability to direct contact with a disease cell or disease site and the cells spread to distant organs. The growth rate of breast tumours under investigation are not disease cells . 10020 ] “ Contact” as referred to herein refers to cells com varies considerably between subjects . Some tumours grow so ing into close proximity with one another such that the direct rapidly that they escape a biannual screening program and effect of one cell on the other may be observed , e .g . an hence show clinical symptoms before detection bymammog immune response , wherein these responses are not mediated raphy . In addition ,mammographic sensitivity is significantly by secondary molecules released from the first cell over a reduced in women with dense breast tissue, often seen in large distance to affect the second cell . Preferably contact pre -menopausal women or those receiving menopausal hor refers to physical contact, or contact that is as close as is mone therapy . Due to the low sensitivity ofmammography in sterically possible, conveniently , cells which contact one women with dense breast tissue , other imaging modalities another are found in the same unit volume, for example within have been introduced in breast cancer screening including 1 cm " . ultrasonography and magnetic resonance imaging (MRI ) . [0021 ] A “ disease cell” is a cell manifesting phenotypic However, ultrasound is very operator - dependent, time- con changes and is present at the disease site at some time during suming, and is associated with many false positive results . its life - span , i . e . in the present case a cancer, preferably breast MRI is expensive , and both the high false positives rate , cancer , cell at the tumour site or which has disseminated from limited resources and lack of universally accepted imagine the tumour. guidelines restrict the use of MRI in a screening setting. The [0022 ] “Moderately or highly ” expressed genes refers to need for improved methods to accurately detect breast cancer, those present in resting cells in a copy number of more than particularly at an early stage , is highly desirable . 30 - 100 copies /cell (assuming an average 3x10 mRNA mol [ 0015 ] We have now identified a new set of probes of sur ecules in a cell ) . prising utility for identifying a cancer, preferably breast can [ 0023 ] Specific probes having the above described proper cer, including early breast cancer , by gene expression profil ties are provided herein . ing of cells of the individual under investigation , e . g . [0024 ] Thus in one aspect , the present invention provides a peripheral blood cells . set of oligonucleotide probes, wherein said set comprises at [ 0016 ] In work leading up to this invention , the inventors least 10 oligonucleotides wherein each of said 10 oligonucle examined the level of expression of a large number of genes otides is selected from an oligonucleotide as set forth in Table in breast cancer patients relative to normal patients . A con 5 or derived from a sequence set forth in Table 5 , or an siderable number of genes were found to exhibit altered oligonucleotide with a complementary sequence to the Table expression and these genes could be classified according to 5 sequence or the derived sequence , or a functionally equiva the number of cross validation models in which they exhib lent oligonucleotide . ited altered expression and were considered informative . [ 0025 ] Preferably , each of said 10 probes corresponds to a Thus, for example , those with 100 % frequency of occurrence different oligonucleotide as set forth in Table 5 , but one or correlate to those which exhibited altered expression and more of said oligonucleotides may be replaced by the corre were considered informative in all cross validation models sponding derived , complementary or functionally equivalent whereas those with 0 % frequency of occurrence exhibited oligonucleotide , i . e . replaced with an oligonucleotide that altered expression and were considered informative in at least will bind to the same gene transcript. If , for example , only one of the cross validation models . As such these genes pro primers are to be used , in all likelihood all oligonucleotides vide a pool from which corresponding probes may be gener will be derived oligonucleotides, e . g . will be parts of the ated , particularly based on their frequency of occurrence , to provided sequences. generate a fingerprint of the expression of these genes in an 10026 ]. The use of such probes in products and methods of individual. Since the expression of these genes is altered in the invention , form further aspects of the invention . the cancer, preferably breast cancer , individual, and may [ 0027 ] Said “ derived ” oligonucleotides include oligonucle hence be considered informative for that state , the generated otides derived from the genes corresponding to the sequences fingerprint from the collection of probes is indicative of that provided in those tables . Table 5 provides gene identifiers for disease relative to the normal state . the various sequences ( i . e . the gene sequence corresponding [ 0017 ] Thus the invention provides a set of oligonucleotide to the oligonucleotide provided ) . This is stated in the column probes which correspond to genes in a cell whose expression entitled " ABI Probe ID ” which provides the ABI 1700 iden is affected in a pattern characteristic of a cancer , preferably tifier . Details of the genes may be obtained from the Panther breast cancer , or a stage thereof, wherein said genes are sys Classification System for genes, transcripts and proteins temically affected by said cancer , preferably breast cancer, or (http :/ / www .pantherdb .org /genes ). Alternatively details may a stage thereof. Preferably said genes are constitutively mod be obtained directly from Applied Biosystems Inc . , CA , erately or highly expressed . Preferably the genes are moder USA . ately or highly expressed in the cells of the sample but not in [0028 ] As referred to herein an " oligonucleotide” is a cells from disease ( cancer, preferably breast cancer ) cells or nucleic acid molecule having at least 6 monomers in the in cells having contacted such disease cells . polymeric structure , i .e . nucleotides or modified forms [0018 ] Such probes, particularly when isolated from cells thereof. The nucleic acid molecule may be DNA , RNA or distant to the site of disease , do not rely on the development of PNA (peptide nucleic acid ) or hybrids thereof or modified disease to clinically recognizable levels and allow detection versions thereof, e . g . chemically modified forms , e . g . LNA of cancer , preferably breast cancer, or a stage thereof very (Locked Nucleic acid ) , by methylation or made up of modi US 2012 /0295815 A1 Nov . 22 , 2012

fied or non -natural bases during synthesis , providing they [ 0035 ] As mentioned above , " derived ” oligonucleotides retain their ability to bind to complementary sequences . Such also include oligonucleotides derived from the genes corre oligonucleotides are used in accordance with the invention to sponding to the sequences ( i . e . the presented oligonucleotides probe target sequences and are thus referred to herein also as or the listed gene sequences ) provided in those tables . In this oligonucleotide probes or simply as “ probes” . case the oligonucleotide forms a part of the gene sequence of which the sequence provided in Table 5 is a part . Table 5 [0029 ] “ Probes” as referred to herein are oligonucleotides provides ABI 1700 gene identifiers and thus the derived oli which bind to the relevant transcript and which allow the gonucleotide may form a part of said gene (or its transcript) or presence or amount of the target molecule to which they bind a complementary sequence thereof. Thus , for example , label to be detected . Such probes may be, for example probes ling probe or primer sequences may be derived from any which act as a label for the target molecule ( referred to here where on the gene to allow specific binding to that gene or its inafter as labelling probes ) or which allow the generation of a transcript . signal by another means , e . g . a primer. [003 ] Preferably the oligonucleotide probes forming said [0030 ] As referred to herein a “ labelling probe” refers to a set are at least 15 bases in length to allow binding of target probe which binds to the target sequence such that the com molecules. Especially preferably said oligonucleotide probes bined target sequence and labelling probe carries a detectable are at least 10 , 20 , 30 , 40 or 50 bases in length , but less than label or which may otherwise be assessed by virtue of the 200 , 150 , 100 or 50 bases, e. g . from 20 to 200 bases in length , formation of that association . For example , this may be e . g . from 30 to 150 bases, preferably 50 - 100 bases in length . achieved by using a labelled probe or the probe may act as a [ 0037 ] When that probe is a primer , similar considerations capture probe of labelled sequences as described hereinafter. apply , but preferably said primers are from 10 - 30 bases in [0031 ] When used as a primer, the probe binds to the target length , e . g . from 15 - 28 bases , e . g . from 20 - 25 bases in length . sequence and optionally together with another relevant Usual considerations apply in the development of primers, primer allows the generation of an amplification product e .g . preferably the primers have a G + C content of 50 -60 % and indicative of the presence of the target sequence which may should end at the 3 '- end in a G or C or CG or GC to increase then be assessed and / or quantified . The primer may incorpo efficiency , the 3 '- ends should not be complementary to avoid rate a label or the amplification process may otherwise incor primer dimers, primer self- complementarity should be porate or reveal a label during amplification to allow detec avoided and runs of 3 ormore Cs or Gs at the 3 ' ends should tion . Any oligonucleotides which bind to the target sequence be avoided . Primers should be of sufficient length to prime the and allow the generation of a detectable signal directly or synthesis of the desired extension product in the presence of indirectly are encompassed . the inducing agent. [0032 ] “ Primers” refer to single or double - stranded oligo [ 0038 ] To identify appropriate primers for performance of nucleotides which hybridize to the target sequence and under the invention , the gene sequences or probe sequences pro appropriate conditions ( i. e . in the presence of nucleotides and vided in the Table may be used to design primers or probes . an inducing agent such as a DNA polymerase and at a suitable Preferably said primers are generated to amplify short DNA temperature and pH ) act as a point of initiation of synthesis to sequences ( e . g . 75 to 600 bases ) . Preferably short amplicons allow amplification of the target sequence through elongation are amplified , e . g . preferably 75 - 150 bases . The probes and from the primer sequence e . g . via PCR . primers can be designed within an exon or may span exon [ 0033 ] In primer based methods, preferably real time quan junction . For example , Table 5 provides the ABImicroarray titative PCR is used as this allows the efficient detection and probe ID and this may be used to identify corresponding ABI quantification of small amounts of RNA in real time. The Taqman assay ID using Panther Classification System for procedure follows the general RT- PCR principle in which Genes, transcripts and Proteins (http / /www .pantherdb . org / mRNA is first transcribed to cDNA which is then used to genes ) Once Taqman assays has been identified they can then amplify short DNA sequences with the help of sequence be obtained from the supplier. Alternatively , the gene names specific primers. Two common methods for detection ofprod and gene symbols can be used to identify the corresponding ucts in real- time PCR are : ( 1 ) non - specific fluorescent dyes gene sequences in public databases, for example The that intercalate with any double - stranded DNA , for example National Center for Biotechnology Information (http :/ /www . SYBR green dye and ( 2 ) sequence -specific DNA probes con ncbi. nlm .nih .gov /) . Alternatively , the oligonucleotide nucle sisting of oligonucleotides that are labelled with a fluorescent otide sequences provided may be used to identify correspond reporter which permits detection only after hybridization of ing gene and transcript by aligning them to known sequences the probe with its complementary DNA target for example the using Nucleotide Blast (Blastn ) program at NCBI. Using the ABI TaqMan System (which is discussed in more detail in the gene or transcript sequence , primers and probes can be Examples ). designed by using freely or commercially available programs [0034 ] An “ oligonucleotide derived from a sequence as set for oligonucleotide and primer design , for example The forth in Table 5 ” (or any other table ) includes a part of a Primer Express Software by Applied Biosystems. sequence disclosed in that Table or its complementary [0039 ] As referred to herein the term " complementary sequence , which satisfies the requirements of the oligonucle sequences ” refers to sequences with consecutive complemen otide probes as described herein , e . g . in length and function . tary bases ( i. e . T : A , G : C ) and which complementary Preferably said parts have the size described hereinafter, for sequences are therefore able to bind to one another through probes ( including primers ) of a suitable size for use in the their complementarity . invention . Thus derived oligonucleotides includes probes 10040 ] Reference to “ 10 oligonucleotides ” refers to 10 dif such as primers which correspond to a part of the disclosed ferent oligonucleotides . Whilst a Table 5 oligonucleotide , a sequence or the complementary sequence . More than one Table 5 derived oligonucleotide and their functional equiva oligonucleotide may be derived from the sequence , e . g . to lent are considered different oligonucleotides , complemen generate a pair of primers and / or a labelling probe. tary oligonucleotides are not considered different. Preferably US 2012 /0295815 A1 Nov . 22 , 2012

however, the at least 10 oligonucleotides are 10 different ably from 10 to 500 , e . g. 10 to 100 , 200 or 300 , especially Table 5 oligonucleotides ( or Table 5 derived oligonucleotides preferably 20 to 100 , e . g . 30 to 100 probes. In some cases less or their functional equivalents) . Thus said 10 different oligo than 10 probes may be used , e . g . from 2 to 9 probes , e . g . 5 to nucleotides are preferably able to bind to 10 different tran 9 probes. scripts . [0046 ] It will be appreciated that increasing the number of [0041 ] Preferably said oligonucleotides are as set forth in probes will prevent the possibility of poor analysis , e . g . mis Table 5 or are derived from a sequence set forth in Table 5 . diagnosis by comparison to other diseases which could simi Said derived oligonucleotides include oligonucleotides larly alter the expression of the particular genes in question . derived from the genes corresponding to the sequences pro Other oligonucleotide probes not described herein may also vided in those tables, or the complementary sequences be present, particularly if they aid the ultimate use of the set of thereof. oligonucleotide probes . However, preferably said set consists (0042 ] In a preferred aspect, said oligonucleotides are as set only of said Table 5 , 7C or 8B oligonucleotides, Table 5 , 7C forth in Table 7C or 8B or are derived from a sequence set or 8B derived oligonucleotides, complementary sequences or forth in Table 7C or B . Oligonucleotides set forth in Table 7C functionally equivalent oligonucleotides, or a sub - set ( e . g . of are the oligonucleotides which appear in that table. Oligo the size and type as described above ) thereof. nucleotides set forth in Table 8B are the oligonucleotides set [ 0047 ] Multiple copies of each unique oligonucleotide forth in Table 5 for which the ABI Nos of Table 5 are given in probe , e . g . 10 ormore copies, may be present in each set , but Table 8B (i . e . the oligonucleotides of Table 8B are obtained constitute only a single probe . by cross - reference to Table 5 ) . The sequences set forth in [ 0048 ] A set of oligonucleotide probes, which may prefer Tables 5 , 7C and 8B include the provided oligonucleotide ably be immobilized on a solid support or have means for such sequences as well as the gene sequences for which the gene immobilization , comprises the at least 10 oligonucleotide identifier (ABI No. ) is given . Said derived oligonucleotides probes selected from those described hereinbefore . As men include oligonucleotides derived from the genes correspond tioned above , these 10 probes must be unique and have dif ing to the sequences provided in those tables , or the comple ferent sequences . Having said this however , two separate mentary sequences thereof. Tables 7C and 8B offer a subset of probes may be used which recognize the same gene but reflect probes from Table 5 which are identified by their ID Nos from different splicing events . However oligonucleotide probes Table 5 . References herein to Table 5 may be considered which are complementary to , and bind to distinct genes are similarly to apply also to Table 7C or 8B . preferred . [0043 ] Especially preferably, the oligonucleotides are [0049 ] When probes of the set are primers , in a preferred selected on the basis of their frequency of occurrence as set aspect pairs of primers are provided . In such cases the refer out in Table 5 , 7C or 8B ( frequency of occurrence information ence to the oligonucleotides that should be present (e . g . 10 for the sequences of Table 8B may be derived from the cor oligonucleotides) should be scaled up accordingly , i. e . 20 responding sequences in Table 5 ). Thus, preferably , said set of oligonucleotides which correspond to 10 pairs of primers , probes are selected from those in Table 5 , 7C or 8B having at each pair being specific for a particular target sequence . In a least 10 % , 20 % , 30 % , 40 % , 50 % , 60 % , 70 % , 80 % or 100 % further alternative , the probes of the set may comprise both occurrence . In a particularly preferred aspect all oligonucle labelling probes and primers directed to a single target otides in the set have the above % occurrence ( or are derived sequence ( e . g . for the Taqman assay described in more detail from such oligonucleotides ) . In an alternative embodiment, hereinafter ) . In this case the reference to oligonucleotides that the oligonucleotides in the set may have 0 , 10 , 20 , 30 , 40 , 50 , should be present ( e . g . 10 oligonucleotides ) should be scaled 60 , 70 , 80 , 90 or 100 % occurrence , i . e . the probes in Table 5 , up to 30 oligonucleotides, i. e . 10 pairs of primers and a 7C or 8B fall into 11 sub - groups from which sets may be corresponding relevant labelled probe for a particular target selected and preferably all the oligonucleotides in the set have sequence . this % occurrence . 10050 ]. Thus in a preferred aspect the set of the invention [ 0044 ] In a preferred embodiment, said set contains all of comprises at least 20 oligonucleotides and said set comprises the probes ( i. e . oligonucleotides ) of Table 5 , 7C or 8B (or their pairs of primers in which each oligonucleotide in said pair of derived , complementary sequences , or functional equiva primers binds to the same transcript or its complementary lents ) or of the sub - sets described above . Thus in one aspect sequence and preferably each of the pairs of primers bind to a the set may contain all of the probes of Table 5 , 7C or 8B (or different transcript. In a further preferred aspect the invention their derived , complementary sequences , or functional provides a set of oligonucleotide probes which comprises at equivalents ) , or in another aspect the set may contain all the least 30 oligonucleotides and said set comprises pairs of probes ( or their derived , complementary sequences , or func primers and a labelled probe for each pair of primers in which tional equivalents ) having 0 , 10 , 20 , 30 , 40 , 50 , 60 , 70 , 80 , 90 each oligonucleotide in said pair ofprimers and said labelled or 100 % occurrence or in another aspect may contain all of probe bind to the same transcript or its complementary the probes ( or their derived , complementary sequences , or sequence and preferably each of the pairs of primers and the functional equivalents ) having at least 0 , 10 , 20 , 30 , 40 , 50 , labelled probe bind to different transcripts . The labelled 60 , 70 , 80 , 90 or 100 % occurrence in the tables . In a preferred probe is “ related ” to its pair of primers insofar as the primers aspect the sets consist of only the above described probes (or bind up or downstream of the target sequence to which the their derived , complementary sequences , or functional labelled probe binds on the same transcript. equivalents ) . 10051] As described herein a “ functionally equivalent” oli [ 0045 ] A “ set” as described refers to a collection of unique gonucleotide to those set forth in Table 5 or derived therefrom oligonucleotide probes ( i. e . having a distinct sequence ) and refers to an oligonucleotide which is capable of identifying preferably consists of less than 1000 oligonucleotide probes, the same gene as an oligonucleotide of Table 5 or derived especially less than 500 , 400 , 300 , 200 or 100 probes , and therefrom , i . e . it can bind to the same mRNA molecule ( or preferably more than 10 , 20 , 30 , 40 or 50 probes, e . g. prefer - DNA ) transcribed from a gene (target nucleic acid molecule ) US 2012 /0295815 A1 Nov . 22 , 2012

as the Table 5 oligonucleotide or the Table 5 derived oligo when sequence identity to only a part of said Table 5 oligo nucleotide ( or its complementary sequence ) . Preferably said nucleotide is present , the sequence identity is high , e . g . at functionally equivalent oligonucleotide is capable of recog least 80 % as described above . nizing , i . e . binding to the same splicing product as a Table 5 [ 0057 ] Functionally equivalent oligonucleotides which sat oligonucleotide or a Table 5 derived oligonucleotide . Prefer isfy the above stated functional requirements include those ably said mRNA molecule is the full length mRNA molecule which are derived from the Table 5 oligonucleotides and also which corresponds to the Table 5 oligonucleotide or the Table those which have been modified by single or multiple nucle 5 derived oligonucleotide . otide base ( or equivalent ) substitution , addition and /or dele [ 0052 ] As referred to herein “ capable ofbinding ” or “ bind tion , but which nonetheless retain functional activity , e . g . ing” refers to the ability to hybridize under conditions bind to the same target molecule as the Table 5 oligonucle described hereinafter . otide or the Table 5 oligonucleotide from which they are [0053 ] Alternatively expressed , functionally equivalent further derived or modified . Preferably said modification is of oligonucleotides ( or complementary sequences ) have from 1 to 50 , e . g . from 10 to 30 , preferably from 1 to 5 bases. sequence identity or will hybridize , as described hereinafter , Especially preferably only minormodifications are present, to a region of the targetmolecule to which molecule a Table 5 e . g . variations in less than 10 bases , e . g . less than 5 base oligonucleotide or a Table 5 derived oligonucleotide or a changes . complementary oligonucleotide binds . Preferably , function 10058 ] Within the meaning of “ addition ” equivalents are ally equivalent oligonucleotides (or their complementary included oligonucleotides containing additional sequences sequences ) hybridize to one of the mRNA sequences which which are complementary to the consecutive stretch of bases corresponds to a Table 5 oligonucleotide or a Table 5 derived on the targetmolecule to which the Table 5 oligonucleotide or oligonucleotide under the conditions described hereinafter or the Table 5 derived oligonucleotide binds . Alternatively the has sequence identity to a part of one of the mRNA sequences addition may comprise a different, unrelated sequence , which which corresponds to a Table 5 oligonucleotide or a Table 5 may for example confer a further property , e . g . to provide a derived oligonucleotide. A “ part ” in this context refers to a means for immobilization such as a linker to bind the oligo stretch of at least 5 , e . g . at least 10 or 20 bases, such as from nucleotide probe to a solid support . 5 to 100 , e . g . 10 to 50 or 15 to 30 bases . [ 0059 ] Particularly preferred are naturally occurring [ 0054 ] In a particularly preferred aspect , the functionally equivalents such as biological variants , e . g . allelic , geo equivalent oligonucleotide binds to all or a part of the region graphical or allotypic variants , e . g . oligonucleotides which of a target nucleic acid molecule (mRNA or cDNA ) to which correspond to a genetic variant , for example as present in a the Table 5 oligonucleotide or Table 5 derived oligonucle different species . otide binds . A “ target” nucleic acid molecule is the gene [0060 ] Functional equivalents include oligonucleotides transcript or related product e . g . mRNA , or cDNA , or ampli with modified bases, e . g . using non -naturally occurring fied product thereof. Said “ region ” of said target molecule to bases . Such derivatives may be prepared during synthesis or which said Table 5 oligonucleotide or Table 5 derived oligo by post production modification . nucleotide binds is the stretch over which complementarity [0061 ] “Hybridizing ” sequences which bind under condi exists. At its largest this region is the whole length of the Table tions of low stringency are those which bind under non 5 oligonucleotide or Table 5 derived oligonucleotide , but may stringent conditions ( for example , 6xSSC / 50 % formamide at be shorter if the entire Table 5 sequence or Table 5 derived room temperature ) and remain bound when washed under oligonucleotide is not complementary to a region of the target conditions of low stringency ( 2xSSC , room temperature , sequence . more preferably 2xSSC , 42° C .) . Hybridizing under high [0055 ] Preferably said part of said region of said target stringency refers to the above conditions in which washing is molecule is a stretch of at least 5 , e . g . at least 10 or 20 bases , performed at 2xSSC , 65° C . (where SSC = 0 . 15M NaCl, such as from 5 to 100 , e . g . 10 to 50 or 15 to 30 bases. This may 0 .015M sodium citrate , pH 7 . 2 ) . for example be achieved by said functionally equivalent oli 10062 ] “ Sequence identity ” as referred to herein refers to gonucleotide having several identical bases to the bases of the the value obtained when assessed using ClustalW ( Thompson Table 5 oligonucleotide or the Table 5 derived oligonucle et al. , 1994 , Nucl . Acids Res . , 22 , p 4673 - 4680 ) with the otide . These bases may be identical over consecutive following parameters : stretches, e . g . in a part of the functionally equivalent oligo Pairwise alignment parameters — Method : accurate , Matrix : nucleotide , or may be present non -consecutively , but provide IUB , Gap open penalty : 15 .00 , Gap extension penalty : 6 .66 ; sufficient complementarity to allow binding to the target Multiple alignment parameters - Matrix : IUB , Gap open sequence . penalty : 15 .00 , % identity for delay : 30 , Negative matrix : no , [0056 ] Thus in a preferred feature, said functionally Gap extension penalty : 6 .66 , DNA transitions weighting : 0 . 5 . equivalent oligonucleotide hybridizes under conditions of [0063 ] Sequence identity at a particular base is intended to high stringency to a Table 5 oligonucleotide or a Table 5 include identical bases which have simply been derivatized . derived oligonucleotide or the complementary sequence [0064 ] As described above , conveniently said set of oligo thereof. Alternatively expressed , said functionally equivalent nucleotide probes may be immobilized on one or more solid oligonucleotide exhibits high sequence identity to all or part supports . Single or preferably multiple copies of each unique of a Table 5 oligonucleotide. Preferably said functionally probe are attached to said solid supports , e . g . 10 or more , e . g . equivalent oligonucleotide has at least 70 % sequence iden at least 100 copies of each unique probe are present. tity , preferably at least 80 % , e . g . at least 90 , 95 , 98 or 99 % , to [ 0065 ] One or more unique oligonucleotide probes may be all of a Table 5 oligonucleotide or a part thereof. As used in associated with separate solid supports which together form a this context, a “ part” refers to a stretch of at least 5 , e .g . at least set of probes immobilized on multiple solid support , e. g . one 10 or 20 bases , such as from 5 to 100 , e . g . 10 to 50 or 15 to 30 or more unique probes may be immobilized on multiple bases , in said Table 5 oligonucleotide . Especially preferably beads, membranes , filters , biochips etc . which together form US 2012 /0295815 A1 Nov . 22 , 2012

a set of probes , which together form modules of the kit surface coatings. Solid supports presenting appropriate moi described hereinafter . The solid support of the differentmod eties for attachment of the binding partner may be produced ules are conveniently physically associated although the sig by routine methods known in the art . nals associated with each probe (generated as described here [ 0074 ] Attachment of appropriate functional groups to the inafter ) must be separately determinable . oligonucleotide probes of the invention may be performed by [0066 ] Alternatively , the probes may be immobilized on ligation or introduced during synthesis or amplification , for discrete portions of the same solid support , e . g . each unique example using primers carrying an appropriate moiety , such oligonucleotide probe , e . g . in multiple copies, may be immo as biotin or a particular sequence for capture . bilized to a distinct and discrete portion or region of a single [0075 ] Conveniently , the set of probes described hereinbe filter or membrane , e .g . to generate an array . fore is provided in kit form . [0067 ] A combination of such techniques may also be used , [0076 ] Thus viewed from a further aspect the present inven e . g . several solid supports may be used which each immobi tion provides a kit comprising a set of oligonucleotide probes lize several unique probes . as described hereinbefore optionally immobilized on one or [ 0068 ] The expression “ solid support " shallmean any solid more solid supports . material able to bind oligonucleotides by hydrophobic , ionic [0077 ] Preferably , said probes are immobilized on a single or covalent bridges . solid support and each unique probe is attached to a different 100691 “ Immobilization ” as used herein refers to reversible region of said solid support . However, when attached to mul or irreversible association of the probes to said solid support tiple solid supports , said multiple solid supports form the by virtue of such binding . If reversible , the probes remain modules which make up the kit . Especially preferably said associated with the solid support for a time sufficient for solid support is a sheet, filter , membrane , plate or biochip . methods of the invention to be carried out . [0078 ] Optionally the kit may also contain information 10070] Numerous solid supports suitable as immobilizing relating to the signals generated by normal or diseased moieties according to the invention , are well known in the art samples ( as discussed in more detail hereinafter in relation to and widely described in the literature and generally speaking , the use of the kits ) , standardizing materials , e . g . mRNA or the solid support may be any of the well -known supports or cDNA from normal and / or diseased samples for comparative matrices which are currently widely used or proposed for purposes, labels for incorporation into cDNA , adapters for immobilization , separation etc . in chemical or biochemical introducing nucleic acid sequences for amplification pur procedures . Such materials include , but are not limited to , any poses , primers for amplification and / or appropriate enzymes , synthetic organic polymer such as polystyrene , polyvinyl buffers and solutions. Optionally said kit may also contain a chloride , polyethylene ; or nitrocellulose and cellulose package insert describing how the method of the invention acetate ; or tosyl activated surfaces; or glass or nylon or any should be performed , optionally providing standard graphs , surface carrying a group suited for covalent coupling of data or software for interpretation of results obtained when nucleic acids . The immobilizing moieties may take the form performing the invention . of particles, sheets , gels , filters , membranes, microfibre [0079 ] The use of such kits to prepare a standard diagnostic strips, tubes or plates , fibres or capillaries , made for example gene transcript pattern as described hereinafter forms a fur of a polymeric material e . g . agarose , cellulose , alginate , ther aspect of the invention . teflon , latex or polystyrene or magnetic beads . Solid supports [0080 ] The set of probes as described herein have various allowing the presentation of an array , preferably in a single uses . Principally however they are used to assess the gene dimension are preferred , e . g . sheets , filters , membranes , expression state of a test cell to provide information relating plates or biochips . to the organism from which said cell is derived . Thus the [0071 ] Attachment of the nucleic acid molecules to the probes are useful in diagnosing, identifying or monitoring a solid support may be performed directly or indirectly . For cancer, preferably breast cancer, or a stage thereof in an example if a filter is used , attachment may be performed by organism . UV - induced crosslinking . Alternatively , attachment may be [0081 ] Thus in a further aspect the invention provides the performed indirectly by the use of an attachment moiety use of a set of oligonucleotide probes or a kit as described carried on the oligonucleotide probes and /or solid support. hereinbefore to determine the gene expression pattern of a Thus for example , a pair of affinity binding partners may be cell which pattern reflects the level of gene expression of used , such as avidin , streptavidin or biotin , DNA or DNA genes to which said oligonucleotide probes bind , comprising binding ( e . g . either the lac I repressor protein or the at least the steps of: lac operator sequence to which it binds ) , antibodies (which [0082 ] a ) isolating mRNA from said cell , which may may be mono - or polyclonal) , antibody fragments or the optionally be reverse transcribed to cDNA ; epitopes or haptens of antibodies . In these cases, one partner [0083 ] b ) hybridizing the mRNA or DNA of step ( a ) to a of the binding pair is attached to ( or is inherently part of ) the set of oligonucleotide probes or a kit as defined herein ; and solid support and the other partner is attached to (or is inher [0084 ] c ) assessing the amount ofmRNA or cDNA hybrid ently part of) the nucleic acid molecules . izing to each of said probes to produce said pattern . 10072 ]. As used herein an " affinity binding pair ” refers to [0085 ] As mentioned previously , the oligonucleotide two components which recognize and bind to one another probes may act as direct labels of the target sequence ( insofar specifically ( i .e . in preference to binding to other molecules ) . as the complex between the target sequence and the probe Such binding pairs when bound together form a complex . carries a label) or may be used as primers . In the case of the [0073 ] Attachment of appropriate functional groups to the former step c )may be performed by any appropriate means of solid support may be performed by methods well known in detecting the hybridized entity , e . g . if the mRNA or cDNA is the art , which include for example , attachment through labelled the retention of label in a kitmay be assessed . In the hydroxyl, carboxyl, aldehyde or amino groups which may be case of primers , those primers may be used to generate an provided by treating the solid support to provide suitable amplification product which may be assessed . In that case in US 2012 /0295815 A1 Nov . 22 , 2012

step b ) said probes are hybridized to the mRNA or cDNA and the estimated residual vector. Although many different meth used to amplify the mRNA or cDNA or a part thereof (of the ods can be used to establish the relationship provided in size described herein for parts or preferred sizes for ampli equation 1 , especially preferably the partial Least Squares cons ) and in step c ) the amount of amplified product is Regression (PLSR ) method is used for establishing the rela assessed to produce the pattern . tionship in equation 1 . [0086 ] In the case of techniques in which both primers and [0092 ] The probes are thus used to generate a pattern which labelling probes are used , in the above method the primers reflects the gene expression of a cell at the time of its isolation . and labelling probes are hybridized to the mRNA or cDNA in The pattern of expression is characteristic of the circum step b ) and used to amplify the mRNA or cDNA or a part stances under which that cells finds itself and depends on the thereof. This amplification causes displacement of probes influences to which the cell has been exposed . Thus , a char binding to relevant target sequences and the generation of a acteristic gene transcript pattern standard or fingerprint ( stan signal. In this case , in step c ) the amount ofmRNA or cDNA dard probe pattern ) for cells from an individual with a cancer , hybridizing to the probes is assessed by determining the pres preferably breast cancer, or a stage thereof may be prepared ence or amount of the signal which is generated . Thus in a and used for comparison to transcript patterns of test cells . preferred aspect, said probes are labelling probes and pairs of This has clear applications in diagnosing, monitoring or iden primers and in step b ) said labelling probes and primers are tifying whether an organism is suffering from a cancer , pref hybridized to said mRNA or cDNA and said mRNA or cDNA erably breast cancer , or a stage thereof. or a part thereof is amplified using said primers , wherein [0093 ] The standard pattern is prepared by determining the when said labelling probe binds to the target sequence it is extent of binding of total mRNA ( or cDNA or related prod displaced during amplification thereby generating a signal uct ), from cells from a sample of one or more organismswith and in step c ) the amount of signal generated is assessed to a cancer, preferably breast cancer , or a stage thereof, to the produce said pattern . All modes of detection of the presence probes . This reflects the level of transcripts which are present or amount of binding of the probes as described herein to the which correspond to each unique probe . The amount of target sequence are covered by the above described method nucleic acid material which binds to the different probes is and methods of the invention described hereinafter . assessed and this information together forms the gene tran [0087 ] The mRNA and cDNA as referred to in this method , script pattern standard of a cancer , preferably breast cancer , or and the methods hereinafter , encompass derivatives or copies a stage thereof. Each such standard pattern is characteristic of of said molecules, e . g . copies of such molecules such as those a cancer, preferably breast cancer, or a stage thereof . produced by amplification or the preparation of complemen (0094 ] In a further aspect therefore , the present invention tary strands, but which retain the identity of the mRNA provides a method of preparing a standard gene transcript sequence , i. e . would hybridize to the direct transcript ( or its pattern characteristic of a cancer , preferably breast cancer , or complementary sequence ) by virtue of precise complemen a stage thereofin an organism comprising at least the steps of: tarity , or sequence identity , over at least a region of said 00951 a ) isolating mRNA from the cells of a sample of one molecule . It will be appreciated that complementarity will not or more organisms having the cancer , preferably breast can exist over the entire region where techniques have been used cer, or a stage thereof, which may optionally be reverse tran which may truncate the transcript or introduce new scribed to cDNA ; sequences , e . g . by primer amplification . For convenience , [0096 ] b ) hybridizing the mRNA or cDNA of step ( a ) to a said mRNA or cDNA is preferably amplified prior to step b ) . set of oligonucleotides or a kit as described hereinbefore As with the oligonucleotides described herein said molecules specific for said cancer, preferably breast cancer , or a stage may be modified , e. g . by using non - natural bases during thereof in an organism and sample thereof corresponding to synthesis providing complementarity remains . Such mol the organism and sample thereof under investigation ; and ecules may also carry additional moieties such as signalling [ 0097 ] c ) assessing the amount ofmRNA or cDNA hybrid or immobilizing means. izing to each of said probes to produce a characteristic pattern [0088 ] The various steps involved in the method of prepar reflecting the level of gene expression of genes to which said ing such a pattern are described in more detail hereinafter . oligonucleotides bind , in the sample with the cancer, prefer [ 0089 ] As used herein " gene expression ” refers to tran ably breast cancer , or a stage thereof. scription of a particular gene to produce a specific mRNA [0098 ] For convenience , said oligonucleotides are prefer product ( i. e . a particular splicing product ) . The level of gene ably immobilized on one or more solid supports . expression may be determined by assessing the level of tran [0099 ] However , in a preferred aspect, said method is per scribed mRNA molecules or cDNA molecules reverse tran formed using primers which amplify the mRNA or cDNA or scribed from the mRNA molecules or products derived from a part thereof and the amount of amplified product is assessed those molecules, e. g . by amplification . to produce the pattern . As described hereinbefore, both [ 0090 ] The “ pattern ” created by this technique refers to labelled probes and primers may be used in preferred aspects information which , for example , may be represented in tabu of the invention . lar or graphical form and conveys information about the sig [0100 ] The standard pattern for various cancers , preferably nal associated with two or more oligonucleotides. Preferably breast cancers, and different stages thereof using particular said pattern is expressed as an array ofnumbers relating to the probes may be accumulated in databases and be made avail expression level associated with each probe . able to laboratories on request. [0091 ] Preferably , said pattern is established using the fol [0101 ] “ Disease ” samples and organisms or “ cancer ” lowing linear model : samples and organisms as referred to herein refer to organ Equation 1 isms ( or samples from the same ) with abnormal cell prolif y = Xb + f eration e . g . in a solid mass such as a tumour. Such organisms wherein , X is the matrix of gene expression data and y is the are known to have , or which exhibit , the cancer ( e . g . breast response variable , b is the regression coefficient vector and f cancer ) or stage thereof under study. US 2012 /0295815 A1 Nov . 22 , 2012

[0102 ] “ Cancer ” as referred to herein includes stomach , manifests the disease in a way which may be objectively lung , breast , prostate gland , bowel, skin , colon and ovary determined , e . g . a tumour, e . g . in breast cancer the site of cancer , preferably breast cancer. disease is the breast. Preferably , peripheral blood is used for [0103 ] “ Breast cancer" as referred to herein includes all diagnosis , and the blood does not require the presence of types of breast cancer including ductal carcinoma in situ malignant or disseminated cells from the cancer in the blood . (DCIS ) , lobular carcinoma in situ (LCIS ), invasive ductal [0108 ] It will however be appreciated that the method of breast cancer , invasive lobular breast cancer, inflammatory preparing the standard transcription pattern and other meth breast cancer, Paget ' s disease and rare types of breast cancer ods of the invention are also applicable for use on living parts such as medullary breast cancer, mucinous (mucoid or col of eukaryotic organisms such as cell lines and organ cultures loid ) breast cancer, tubular breast cancer , adenoid cystic car and explants . cinoma of the breast, papillary breast cancer , metaplastic [0109 ] As used herein , reference to " corresponding ” breast cancer, angiosarcoma of the breast, phyllodes or sample etc . refers to cells preferably from the same tissue , cytosarcoma phyllodes , lymphoma of the breast and basal body fluid or body waste , but also includes cells from tissue , type breast cancer. body fluid or body waste which are sufficiently similar for the [0104 ] The methods described herein may be used to iden purposes of preparing the standard or test pattern . When used tify or diagnose whether an individualhas any cancer, e . g . any in reference to genes “ corresponding ” to the probes, this breast cancer , or whether a particular cancer , e . g . particular refers to genes which are related by sequence ( which may be breast cancer is present by developing the appropriate classi complementary ) to the probes although the probes may fication models for those conditions . reflect different splicing products of expression . [0105 ] “ Stages” thereof refer to different stages of cancer [0110 ] " Assessing ” as used herein refers to both quantita which may or may not exhibit particular physiological or tive and qualitative assessment which may be determined in metabolic changes , but do exhibit changes at the genetic level absolute or relative terms. which may be detected as altered gene expression . It will be [0111 ] The invention may be put into practice as follows. appreciated that during the course of cancer (or its treatment) [0112 ] To prepare a standard transcript pattern for a cancer, the expression of different transcripts may vary . Thus at dif preferably breast cancer, or a stage thereof, sample mRNA is ferent stages, altered expression may not be exhibited for extracted from the cells of tissues, body fluid or body waste particular transcripts compared to “ normal” samples . How according to known techniques ( see for example Sambrook ever , combining information from several transcripts which et . al . ( 1989 ), Molecular Cloning : A laboratory manual , 2nd exhibit altered expression at one or more stages through the Ed ., Cold Spring Harbor Laboratory Press , Cold Spring Har course of the cancer can be used to provide a characteristic bor, N . Y . ) from an individual or organism with a cancer, pattern which is indicative of a particular stage of the cancer. preferably breast cancer, or a stage thereof. Thus for example different stages in cancer, e . g . pre -stage I [0113 ] Owing to the difficulties in working with RNA , the ( e . g . stage 0 ) , stage I , stage II , II or IV can be identified . In RNA is preferably reverse transcribed to form first strand preferred aspects , the methods described herein may be used cDNA . Cloning of the cDNA or selection from , or using, a to detect stage 0 cancers, e. g. in the case of breast cancer, cDNA library is not however necessary in this or other meth DCIS or LCIS , e .g . before the breast shows any signs of ods of the invention . Preferably , the complementary strands metastasis and/ or hasmoved beyond the breast ducts and can of the first strand cDNAs are synthesized , i . e . second strand be used to distinguish between different stages of the disease . cDNAs, but this will depend on which relative strands are [0106 ] " Normal" as used herein refers to organisms or present in the oligonucleotide probes. The RNA may however samples which are used for comparative purposes . Preferably , alternatively be used directly without reverse transcription these are “ normal ” in the sense that they do not exhibit any and may be labelled if so required . indication of, or are not believed to have , any disease or [0114 ] Preferably the cDNA strands are amplified by condition that would affect gene expression , particularly in known amplification techniques such as the polymerase chain respect of cancer, e . g . breast cancer for which they are to be reaction (PCR ) by the use of appropriate primers . Alterna used as the normal standard . However, it will be appreciated tively , the cDNA strands may be cloned with a vector , used to that different stages of a cancer, preferably breast cancer, may transform a bacteria such as E . coli which may then be grown be compared and in such cases, the “ normal” sample may to multiply the nucleic acid molecules . When the sequence of correspond to the earlier stage of cancer, preferably breast the cDNAs are not known , primers may be directed to regions cancer . of the nucleic acid molecules which have been introduced . [0107 ] As used herein a “ sample ” refers to any material Thus for example , adapters may be ligated to the cDNA obtained from the organism , e . g . or non -human ani molecules and primers directed to these portions for amplifi mal under investigation which contains cells and includes , cation of the cDNA molecules . Alternatively , in the case of tissues , body fluid or body waste or in the case of prokaryotic eukaryotic samples, advantage may be taken of the polyA tail organisms, the organism itself. “ Body fluids” include blood , and cap of the RNA to prepare appropriate primers . saliva , spinal fluid , semen , lymph . “ Body waste ” includes [0115 ] To produce the standard diagnostic gene transcript urine , expectorated matter (pulmonary patients ), faeces etc . pattern or fingerprint for a cancer, preferably breast cancer, or " Tissue samples " include tissue obtained by biopsy, by sur a stage thereof, the above described oligonucleotide probes gical interventions or by othermeans e . g . placenta . Preferably are used to probe mRNA or DNA of the diseased sample to however, the samples which are examined are from areas of produce a signal for hybridization to each particular oligo the body not apparently affected by the cancer, preferably nucleotide probe species , i. e . each unique probe. A standard breast cancer. The cells in such samples are not disease cells , control gene transcript pattern may also be prepared if desired i. e . cancer cells , have not been in contact with such disease using mRNA or cDNA from a normal sample . Thus, mRNA cells and do not originate from the site of the cancer. The “ site or cDNA is brought into contact with the oligonucleotide of disease ” is considered to be that area of the body which probe under appropriate conditions to allow hybridization . US 2012 /0295815 A1 Nov . 22 , 2012

Alternatively , specific primer sequences for highly and mod fied by other physical properties , such as their absorbance, erately expressed genes can be designed and methods such as and in which case the signalling means is the complex itself . quantitative RT- PCR can be used to determine the levels of highly and moderately expressed genes, particularly the [0122 ] The amount of signal associated with each oligo genes as described herein . Hence , a skilled practitioner may nucleotide probe is then assessed . The assessment may be use a variety of techniques which are known in the art for quantitative or qualitative and may be based on binding of a determining the relative level of mRNA in a biological single transcript species ( or related cDNA or other products ) sample . to each probe, or binding of multiple transcript species to [ 0116 ] When multiple samples are probed , this may be multiple copies of each unique probe . It will be appreciated performed consecutively using the same probes, e .g . on one that quantitative results will provide further information for or more solid supports , i. e . on probe kit modules, or by simul the transcript fingerprint of a cancer, preferably breast cancer , taneously hybridizing to corresponding probes , e . g . the mod or a stage thereof which is compiled . This data may be ules of a corresponding probe kit . expressed as absolute values in the case of macroarrays ) or [0117 ] To identify when hybridization occurs and obtain an may be determined relative to a particular standard or refer indication of the number of transcripts/ cDNA molecules ence e .g . a normal control sample . which become bound to the oligonucleotide probes , it is [0123 ] Furthermore it will be appreciated that the standard necessary to identify a signal produced when the transcripts diagnostic gene pattern transcript may be prepared using one (or related molecules ) hybridize ( e. g . by detection of double or more disease ( cancer, preferably breast cancer ) samples stranded nucleic acid molecules or detection of the number of ( and normal samples if used ) to perform the hybridization molecules which become bound , after removing unbound step to obtain patterns not biased towards a particular indi molecules , e . g . by washing , or by detection of a signal gen vidual' s variations in gene expression . erated by an amplified product ). [0124 ] The use of the probes to prepare standard patterns [0118 ] In order to achieve a signal, either or both compo and the standard diagnostic gene transcript patterns thus pro nents which hybridize ( i. e . the probe and the transcript ) may duced for the purpose of identification or diagnosis or moni carry or form a signalling means or a part thereof. This “ sig toring of a cancer , preferably breast cancer, or a stage thereof nalling means” is any moiety capable of direct or indirect in a particular organism forms a further aspect of the inven detection by the generation or presence of a signal. The signal tion . may be any detectable physical characteristic such as con [0125 ] Once a standard diagnostic fingerprint or pattern has ferred by radiation emission, scattering or absorption proper been determined for a cancer, preferably breast cancer , or a ties, magnetic properties , or other physical properties such as stage thereof using the selected oligonucleotide probes, this charge , size or binding properties of existing molecules ( e . g . information can be used to identify the presence , absence or labels ) or molecules which may be generated ( e . g . gas emis extent or stage of the cancer , preferably breast cancer, in a sion etc . ) . Techniques are preferred which allow signal ampli different test organism or individual . fication , e . g . which produce multiple signal events from a [0126 ] To examine the gene expression pattern of a test single active binding site , e . g . by the catalytic action of sample , a test sample of tissue, body fluid or body waste enzymes to produce multiple detectable products . containing cells , corresponding to the sample used for the [0119 ] Conveniently the signalling means may be a label preparation of the standard pattern , is obtained from a patient which itself provides a detectable signal. Conveniently this or the organism to be studied . A test gene transcript pattern is may be achieved by the use of a radioactive or other label then prepared as described hereinbefore as for the standard which may be incorporated during cDNA production , the pattern . preparation of complementary cDNA strands, during ampli [0127 ] In a further aspect therefore , the present invention fication of the targetmRNA / cDNA or added directly to target provides a method of preparing a test gene transcript pattern nucleic acid molecules. comprising at least the steps of: [0120 ] Appropriate labels are those which directly or indi [0128 ] a ) isolating mRNA from the cells ofa sample of said rectly allow detection or measurement of the presence of the transcripts / cDNA . Such labels include for example radiola test organism , which may optionally be reverse transcribed to bels , chemical labels , for example chromophores or fluoro cDNA ; phores ( e . g . dyes such as fluorescein and rhodamine ), or [0129 ] b ) hybridizing the mRNA or cDNA of step ( a ) to a reagents of high electron density such as ferritin , haemocya set of oligonucleotides or a kit as described hereinbefore nin or colloidal gold . Alternatively, the label may be an specific for a cancer, preferably breast cancer, or a stage enzyme, for example peroxidase or alkaline phosphatase , thereof in an organism and sample thereof corresponding to wherein the presence of the enzyme is visualized by its inter the organism and sample thereof under investigation ; and action with a suitable entity, for example a substrate . The [0130 ] c ) assessing the amount ofmRNA or cDNA hybrid labelmay also form part of a signalling pair wherein the other izing to each of said probes to produce said pattern reflecting member of the pair is found on , or in close proximity to , the the level of gene expression of genes to which said oligo oligonucleotide probe to which the transcript/ cDNA binds , nucleotides bind , in said test sample . for example , a fluorescent compound and a quench fluores [0131 ] In a preferred aspect, said method is performed cent substrate may be used . A label may also be provided on using primers which amplify the mRNA or cDNA or a part a different entity , such as an antibody , which recognizes a thereof and the amount of amplified product is assessed to peptide moiety attached to the transcripts / cDNA , for example produce the pattern . As described hereinbefore , both labelled attached to a base used during synthesis or amplification . probes and primers may be used in preferred aspects of the [ 0121 ] A signal may be achieved by the introduction of a invention . label before, during or after the hybridization step . Alterna - (0132 ] This test pattern may then be compared to one or tively , the presence of hybridizing transcripts may be identi more standard patterns to assess whether the sample contains US 2012 /0295815 A1 Nov . 22 , 2012

cells which exhibit gene expression indicative of the indi Although this can be established by obtaining standard devia vidual having a cancer, preferably breast cancer , or a stage tions for several representative samples binding to the probes thereof . to develop the standard , it will be appreciated that single [ 0133 ] Thus viewed from a further aspect the present inven samples may be sufficient to generate the standard pattern to tion provides a method of diagnosing or identifying or moni identify a cancer , preferably breast cancer , if the test sample toring a cancer, preferably breast cancer , or a stage thereof in exhibits close enough correlation to that standard . Conve an organism , comprising the steps of: niently , the presence , absence , or extent of a cancer , prefer [0134 ] a ) isolatingmRNA from the cells of a sample of said ably breast cancer, or a stage thereof in a test sample can be organism , which may optionally be reverse transcribed to predicted by inserting the data relating to the expression level DNA ; of informative probes in test sample into the standard diag 0135 ] b ) hybridizing the mRNA or DNA of step ( a ) to a nostic probe pattern established according to equation 1 . set of oligonucleotides or a kit as described hereinbefore 10143 ) Data generated using the above mentioned methods specific for said cancer, preferably breast cancer, or a stage may be analysed using various techniques from the most thereof in an organism and sample thereof corresponding to basic visual representation ( e . g . relating to intensity ) to more the organism and sample thereof under investigation ; complex data manipulation to identify underlying patterns [0136 ] c ) assessing the amount ofmRNA or DNA hybrid which reflect the interrelationship of the level of expression of izing to each of said probes to produce a characteristic pattern each gene to which the various probes bind , which may be reflecting the level of gene expression of genes to which said quantified and expressed mathematically . Conveniently , the oligonucleotides bind , in said sample; and raw data thus generated may be manipulated by the data [0137 ] d ) comparing said pattern to a standard diagnostic processing and statistical methods described hereinafter , par pattern prepared according to the method of the invention ticularly normalizing and standardizing the data and fitting using a sample from an organism corresponding to the organ the data to a classification model to determine whether said ism and sample under investigation to determine the degree of test data reflects the pattern of a cancer, preferably breast correlation indicative of the presence of said cancer , prefer ably breast cancer, or a stage thereof in the organism under cancer, or a stage thereof. investigation . [0144 ] The methods described herein may be used to iden [0138 ] The method up to and including step c ) is the prepa tify ,monitor or diagnose a cancer, preferably breastcancer , or ration of a test pattern as described above . its stage or progression , for which the oligonucleotide probes [0139 ] In a preferred aspect, said method is performed are informative . “ Informative ” probes as described herein , using primers which amplify the mRNA or DNA or a part are those which reflect genes which have altered expression in thereof and the amount of amplified product is assessed to the cancer , preferably breast cancer, in question , or particular produce the pattern . As described hereinbefore , both labelled stages thereof. Individual probes described herein may not be probes and primers may be used in preferred aspects of the sufficiently informative for diagnostic purposes when used invention . alone , but are informative when used as one of several probes [0140 ] As referred to herein , “ diagnosis ” refers to determi to provide a characteristic pattern , e . g . in a set as described nation of the presence or existence of a cancer, preferably hereinbefore . breast cancer, or a stage thereofin an organism . “ Monitoring ” [0145 ] Preferably said probes correspond to genes which refers to establishing the extent of a cancer, preferably breast are systemically affected by a cancer, preferably breast can cancer , particularly when an individual is known to be suffer cer, or a stage thereof. Especially preferably said genes , from ing from cancer , preferably breast cancer, for example to which transcripts are derived which bind to probes of the monitor the effects of treatment or the development of cancer, invention , are moderately or highly expressed . The advantage preferably breast cancer, e .g . to determine the suitability of a of using probes directed to moderately or highly expressed treatment or provide a prognosis . In a preferred aspect, the genes is that smaller clinical samples are required for gener patient may be monitored after treatment, e .g . by surgery , ating the necessary gene expression data set, e . g . less than 1 radiation and/ or chemotherapy to determine the efficacy of ml blood samples . the treatment by reversion to normal patterns of expression . [0146 ] Furthermore , it has been found that such genes [0141 ] Thus in a preferred aspect the present invention which are already being actively transcribed tend to be more provides a method ofmonitoring a cancer , preferably breast prone to being influenced , in a positive or negative way, by cancer, or a stage thereof in an organism , comprising the steps new stimuli . In addition , since transcripts are already being of a ) to d ) as described above wherein said monitoring is produced at levels which are generally detectable , small performed after treatment of said cancer , preferably breast changes in those levels are readily detectable as for example , cancer, in said organism to determine the efficacy of said a certain detectable threshold does not need to be reached . treatment. The degree of correlation between the pattern gen [0147 ] Thus in a further aspect the present invention pro erated for the sample and the standard cancer , preferably vides a set of probes as described hereinbefore for use in breast cancer ( or stage thereof ) will indicate whether gene diagnosis or identification or monitoring the progression of a expression typical of cancer, preferably breast cancer, is still cancer, preferably breast cancer, or a stage thereof. present and hence the success of the treatment. Reversion to [0148 ] The diagnostic method may be used alone as an normal expression patterns (by comparison with normal stan alternative to other diagnostic techniques or in addition to dard patterns ) are indicative of successful treatment. such techniques . For example , methods of the invention may [ 0142 ] The presence of a cancer, preferably breast cancer, be used as an alternative or additive diagnostic measure to or a stage thereof may be determined by determining the diagnosis using imaging techniques such as Magnetic Reso degree of correlation between the standard and test samples ' nance Imagine (MRI ) , ultrasound imaging , nuclear imaging patterns . This necessarily takes into account the range of or X -ray imaging , for example in the identification and/ or values which are obtained for normal and diseased samples. diagnosis of tumours . US 2012 /0295815 A1 Nov . 22 , 2012

[0149 ] The methods of the invention may be performed on tion with probes disclosed herein . The method also describes cells from prokaryotic or eukaryotic organisms which may be the statisticalmethods used for diagnosis of samples once the any eukaryotic organisms such as human beings , other mam probes have been selected . mals and animals , birds , insects , fish and plants , and any [0154 ] The immobilized probes can be derived from vari prokaryotic organism such as a bacteria . ous unrelated or related organisms; the only requirement is that the immobilized probes should bind specifically to their 10150 ] Preferred non -human animals on which the meth homologous counterparts in test organisms. Probes can also ods of the invention may be conducted include , but are not be derived or selected from commercially available or public limited to mammals , particularly primates, domestic animals , databases and immobilized on solid supports , or asmentioned livestock and laboratory animals . Thus preferred animals for above they can be randomly picked and isolated from a cDNA diagnosis include mice, rats , guinea pigs, cats , dogs , pigs, library and immobilized on a solid support. cows, goats , sheep , horses . Particularly preferably a cancer, [0155 ] The length of the probes immobilised on the solid preferably breast cancer, of is diagnosed , identified support should be long enough to allow for specific binding to or monitored . the target sequences . The immobilised probes can be in the [ 0151] As described above , the sample under study may be form of DNA , RNA or their modified products or PNAS any convenient sample which may be obtained from an organ (peptide nucleic acids ) . Preferably, the probes immobilised ism . Preferably however, as mentioned above , the sample is should bind specifically to their homologous counterparts obtained from a site distant to the site of disease and the cells representing highly and moderately expressed genes in test in such samples are not disease cells , have not been in contact organisms. Conveniently the probes which are used are the with such cells and do not originate from the site of the probes described herein . disease . In such cases , although preferably absent, the sample [0156 ] The gene expression pattern of cells in biological may contain cells which do not fulfil these criteria . However , samples can be generated using prior art techniques such as since the probes of the invention are concerned with tran microarray or macroarray as described below or using meth scripts whose expression is altered in cells which do satisfy ods described herein . Several technologies have now been these criteria , the probes are specifically directed to detecting developed for monitoring the expression level of a large num changes in transcript levels in those cells even if in the pres ber of genes simultaneously in biological samples , such as , ence of other, background cells . high - density oligoarrays (Lockhart et al ., 1996 , Nat . Biotech . , [0152 ] The methods of generating standard and test pat 14 , p 1675 -1680 ), cDNA microarrays (Schena et al, 1995 , terns and diagnostic techniques rely on the use of informative Science , 270 , p 467 -470 ) and cDNA macroarrays (Maier E et oligonucleotide probes to generate the gene expression data . al. , 1994 , Nucl . Acids Res. , 22 , p 3423 -3424 ; Bernard et al. , In some cases it will be necessary to select these informative 1996 , Nucl . Acids Res ., 24 , p 1435 - 1442 ) . probes for a particular method , e . g . to diagnose a particular [0157 ] In high -density oligoarrays and cDNA microarrays , cancer, preferably breast cancer, or stage thereof, from a hundreds and thousands of probe oligonucleotides or cDNAs , selection of available probes , e . g . the Table 5 oligonucle are spotted onto glass slides or nylon membranes , or synthe otides, the Table 5 derived oligonucleotides , their comple sized on biochips. The mRNA isolated from the test and mentary sequences and functionally equivalent oligonucle reference samples are labelled by reverse transcription with a otides . Said derived oligonucleotides include red or green fluorescent dye , mixed , and hybridised to the oligonucleotides derived from the genes corresponding to the microarray . After washing , the bound fluorescent dyes are sequences provided in those tables for which gene identifiers detected by a laser , producing two images , one for each dye . are provided . The following methodology describes a conve The resulting ratio of the red and green spots on the two nient method for identifying such informative probes , or images provides the information about the changes in expres more particularly how to select a suitable sub - set of probes sion levels of genes in the test and reference samples . Alter from the probes described herein . natively , single channel ormultiple channel microarray stud [ 0153 ] Probes for the analysis of a particular cancer , pref ies can also be performed . erably breast cancer, or stage thereof, may be identified in a [0158 ] The generated gene expression data needs to be number of ways known in the prior art , including by differ preprocessed since , several factors can affect the quality and ential expression or by library subtraction ( see for example quantity of the hybridising signals . For example , variations in WO98/ 49342 ) . As described in WO04 /046382 and as the quality and quantity of mRNA isolated from sample to described hereinafter, in view of the high information content sample , subtle variations in the efficiency of labelling target of most transcripts, as a starting point one may also simply molecules during each reaction , and variations in the amount analyse a random sub -set of mRNA or cDNA species corre of unspecific binding between different microarrays can all sponding to the family of sequences described herein and pick contribute to noise in the acquired data set that must be the most informative probes from that sub -set . In the present corrected for prior to analysis . For example , measurements case, probes from which the selection may be made are pro with low signal /noise ratio can be removed from the data set vided . The following method describes the use of immobi prior to analysis . lized oligonucleotide probes ( e . g . the probes of the invention ) 101591. The data can then be transformed for stabilizing the to which mRNA (or related molecules ) from different variance in the data structure and normalized for the differ samples are bound to identify which probes are the most ences in probe intensity . Several transformation techniques informative to identify a cancer , preferably breast cancer, e . g . have been described in the literature and a brief overview can a disease sample . Alternatively, the sub - sets described here be found in Cui, Kerr and Churchill http :/ / www . jax .org / re inbefore may be used for the methods described herein . The search /churchill /research / expression /Cui - Transform .pdf . method below describes how to identify sub - sets of probes Several methods have been described for normalizing gene from those which are disclosed herein or how to identify expression data ( Richmond and Somerville , 2000 , Current additional informative probes that could be used in conjunc Opin . Plant Biol. , 3 , p 108 - 116 ; Finkelstein et al . , 2001, In US 2012 /0295815 A1 Nov . 22 , 2012

“ Methods of Microarray Data Analysis. Papers from [0164 ] Examples of various clustering techniques that have CAMDA, Eds. Lin & Johnsom , Kluwer Academic , p 57- 68 ; been used for gene expression analysis include hierarchical Yang et al. , 2001 , In “ Optical Technologies and Informatics ” , clustering (Eisen et al. , 1998 , supra ; Alizadeh et al. 2000 , Eds. Bittner, Chen , Dorsel & Dougherty , Proceedings of supra ; Perou et al. 2000 , supra ; Ross et al , 2000 , supra ) , SPIE , 4266 , p 141- 152 ; Dudoit et al, 2000 , J. Am . Stat . Ass ., K -means clustering (Herwig et al ., 1999 , supra ; Tavazoie et 97 , p 77 - 87 ; Alter et al 2000 , supra ; Newton et al. , 2001, J . al, 1999, Nature Genetics , 22 ( 3 ), p . 281- 285 ), gene shaving Comp. Biol. , 8 , p 37 -52 ). Generally , a scaling factor or func (Hastie et al ., 2000 , Genome Biology , 1 ( 2 ) , research 0003 . 1 tion is first calculated to correct the intensity effect and then 0003 .21 ) , block clustering ( Tibshirani et al. , 1999 , Tech used for normalising the intensities . The use of external con report Univ Stanford .) Plaid model (Lazzeroni , 2002 , Stat. trols has also been suggested for improved normalization . Sinica, 12 , p 61- 86 ), and self -organizing maps ( Tamayo et al. [0160 ] One other major challenge encountered in large 1999 , supra ). Also , related methods ofmultivariate statistical scale gene expression analysis is that of standardization of analysis , such as those using the singular value decomposi data collected from experiments performed at differenttimes . tion ( Alter et al. , 2000 , PNAS , 97 ( 18 ) , p 10101 - 10106 ; Ross We have observed that gene expression data for samples et al. 2000 , supra ) or multidimensional scaling can be effec acquired in the same experiment can be efficiently compared tive at reducing the dimensions of the objects under study. following background correction and normalization . How [0165 ] However, methods such as cluster analysis and sin ever , the data from samples acquired in experiments per gular value decomposition are purely exploratory and only formed at different times requires further standardization provide a broad overview of the internal structure present in prior to analysis . This is because subtle differences in experi the data . They are unsupervised approaches in which the mental parameters between different experiments , for available information concerning the nature of the class under example, differences in the quality and quantity of mRNA investigation is not used in the analysis . Often , the nature of extracted at different times , differences in time used for target the biological perturbation to which a particular sample has molecule labelling , hybridization time or exposure time, can been subjected is known. For example , it is sometimes known affect themeasured values . Also , factors such as the nature of whether the sample whose gene expression pattern is being the sequence of transcripts under investigation ( their GC con analysed derives from a diseased or healthy individual. In tent) and their amount in relation to the each other determines such instances , discriminant analysis can be used for classi how they are affected by subtle variations in the experimental fying samples into various groups based on their gene expres processes. They determine , for example , how efficiently first sion data . strand cDNAs, corresponding to a particular transcript , are [0166 ] In such an analysis one builds the classifier by train transcribed and labelled during first strand synthesis , or how ing the data that is capable of discriminating between member efficiently the corresponding labelled target molecules bind and non -members of a given class. The trained classifier can to their complementary sequences during hybridization . then be used to predict the class of unknown samples . Batch to batch differences in the manufacturing lots is also a Examples of discrimination methods that have been major factor for variation in the generated expression data . described in the literature include Support Vector Machines [ 0161 ] Failure to properly address and rectify for these ( Brown et al, 2000 , PNAS, 97 , p 262 - 267 ) , Nearest Neigh influences leads to situations where the differences between bour (Dudoit et al ., 2000 , supra ), Classification trees (Dudoit the experimental series may overshadow the main informa et al. , 2000 , supra ) , Voted classification (Dudoit et al. , 2000 , tion of interest contained in the gene expression data set, i . e . supra ) , Weighted Gene voting (Golub et al. 1999 , supra ) , and the differences within the combined data from the different Bayesian classification (Keller et al. 2000 , Tec report Univ of experimental series . Hence , when required the expression Washington ) . Also a technique in which PLS ( Partial Least data should be batch -adjusted prior to data analysis . Square ) regression analysis is first used to reduce the dimen [0162 ] Monitoring the expression of a large number of sions in the gene expression data set followed by classifica genes in several samples leads to the generation of a large tion using logistic discriminant analysis and quadratic dis amount of data that is too complex to be easily interpreted . criminant analysis ( LD and QDA ) has been described Several unsupervised and supervised multivariate data analy (Nguyen & Rocke , 2002, Bioinformatics, 18 , p 39 - 50 and sis techniques have already been shown to be useful in 1216 - 1226 ). extracting meaningful biological information from these [0167 ] A challenge that gene expression data poses to clas large data sets . Cluster analysis is by far the most commonly sical discriminatory methods is that the number of genes used technique for gene expression analysis , and has been whose expression are being analysed is very large compared performed to identify genes that are regulated in a similar to the number of samples being analysed . However in most manner , and or identifying new /unknown tumour classes cases only a small fraction of these genes are informative in using gene expression profiles ( Eisen et al. , 1998 , PNAS , 95 , discriminant analysis problems. Moreover, there is a danger p 14863 - 14868 , Alizadeh et al. 2000 , supra , Perou et al. 2000 , that the noise from irrelevant genes can mask or distort the Nature , 406 , p 747 -752 ; Ross et al , 2000 , Nature Genetics, information from the informative genes . Several methods 24 ( 3 ) , p 227 - 235 ; Herwig et al. , 1999 , Genome Res. , 9 , p have been suggested in literature to identify and select genes 1093 - 1105 ; Tamayo et al, 1999 , Science , PNAS , 96 , p 2907 that are informative in microarray studies , for example , t - sta 2912 ). tistics (Dudoit et al, 2002 , J . Am . Stat . Ass ., 97 , p 77 - 87 ) , [0163 ] In the clustering method , genes are grouped into analysis of variance (Kerr et al. , 2000 , PNAS , 98 , p 8961 functional categories ( clusters) based on their expression pro 8965 ) , Neighbourhood analysis (Golub et al, 1999 , supra ), file , satisfying two criteria : homogeneity — the genes in the Ratio of between groups to within groups sum of squares same cluster are highly similar in expression to each other; (Dudoit et al. , 2002 , supra ) , Non parametric scoring (Park et and separation - genes in different clusters have low similar al. , 2002 , Pacific Symposium on Biocomputing , p 52 -63 ) and ity in expression to each other. Likelihood selection (Keller et al. , 2000 , supra ). US 2012 /0295815 A1 Nov . 22 , 2012

[0168 ] In the methods described herein the gene expression can be used for prediction . Moreover, use of fewer genes for data thathas been normalized and standardized is analysed by the purpose of providing diagnosis will reduce the cost of the using Partial Least Squares Regression (PLSR ) . Although diagnostic product. In this way informative probes which PLSR is primarily a method used for regression analysis of would bind to the genes of relevance may be identified . continuous data , it can also be utilized as a method formodel 10173 ] We have found that after a calibration model has building and discriminant analysis using a dummy response been built, statistical techniques like Jackknife (Effron , 1982 , matrix based on a binary coding . The class assignment is The Jackknife , the Bootstrap and other resampling plans. based on a simple dichotomous distinction such as breast Society for Industrial and Applied mathematics , Philadel cancer ( class 1 )/ healthy ( class 2 ) , or a multiple distinction phia , USA ) , based on resampling methodology , can be effi based on multiple disease diagnosis such as breast cancer ciently used to select or confirm significant variables (infor ( class 1 ) / ovarian cancer ( class 2 )/ healthy ( class 3 ) . The list of mative probes ) . The approximate uncertainty variance of the diseases for classification can be increased depending upon PLS regression coefficients B can be estimated by : the samples available corresponding to other cancers or stages thereof. [0169 ] PLSR applied as a classification method is referred to as PLS -DA (DA standing for Discriminant analysis ) . PLS $ B = m =ŽCB 1 –Bw8v ? DA is an extension of the PLSR algorithm in which the Y -matrix is a dummy matrix containing n rows ( correspond ing to the number of samples ) and K columns ( corresponding where to the number of classes ) . The Y -matrix is constructed by S ? B = estimated uncertainty variance of B ; inserting 1 in the kth column and - 1 in all the other columns B = the regression coefficient at the cross validated rank A if the corresponding ith object of X belongs to class k . By using all the N objects ; regressing Y onto X , classification of a new sample is Bm = the regression coefficient at the rank A using all objects achieved by selecting the group corresponding to the largest except the object( s ) left out in cross validation segment m ; component of the fitted , ? (x ) = (?i ( x ), ?2( x ) , . . . , ?z( x )) . Thus, and in a - 1 / 1 response matrix , a prediction value below O means g = scaling coefficient ( here : g = 1 ) . that the sample belongs to the class designated as - 1, while a [0174 ] In our approach , Jackknife has been implemented prediction value above 0 implies that the sample belongs to together with cross - validation . For each variable the differ the class designated as 1. ence between the B - coefficients B , in a cross - validated sub [0170 ] It is usually recommended to use PLS -DA as a start model and B tot for the total model is first calculated . The sum ing point for the classification problem due to its ability to of the squares of the differences is then calculated in all handle collinear data , and the property of PLSR as a dimen sub -models to obtain an expression of the variance of the B ; sion reduction technique. Once this purpose has been satis estimate for a variable . The significance of the estimate of B ; fied , it is possible to use other methods such as Linear dis is calculated using the t -test . Thus , the resulting regression criminant analysis , LDA , that has been shown to be effective coefficients can be presented with uncertainty limits that cor in extracting further information , Indahl et al. ( 1999 , Chem . respond to 2 Standard Deviations , and from that significant and Intell. Lab . Syst . , 49 , p 19 - 31 ) . This approach is based on variables are detected . first decomposing the data using PLS - DA , and then using the [0175 ] No further details as to the implementation or use of scores vectors ( instead of the original variables ) as input to this step are provided here since this has been implemented in LDA . Further details on LDA can be found in Duda and Hart commercially available software , The Unscrambler , CAMO ( Classification and Scene Analysis , 1973 , Wiley , USA ). ASA , Norway . Also , details on variable selection using Jack [0171 ] The next step following model building is of model knife can be found in Westad & Martens (2000 , J . Near Inf. validation . This step is considered to be amongst the most Spectr. , 8, p 117 - 124 ). important aspects of multivariate analysis, and tests the [0176 ] The following approach can be used to select infor " goodness ” of the calibration model which has been built . In mative probes from a gene expression data set: this work , a cross validation approach has been used for [0177 ] a ) keep out one unique sample (including its repeti validation . In this approach , one or a few samples are kept out tions if present in the data set ) per cross validation segment; in each segment while the model is built using a full cross [0178 ] b ) build a calibration model ( cross validated seg validation on thebasis of the remaining data . The samples left ment ) on the remaining samples using PLSR - DA ; out are then used for prediction /classification . Repeating the [0179 ] c ) select the significant genes for the model in step b ) simple cross- validation process several times holding differ using the Jackknife criterion ; ent samples out for each cross- validation leads to a so - called [0180 ] d ) repeat the above 3 steps until all the unique double cross - validation procedure . This approach has been samples in the data set are kept out once ( as described in step shown to work well with a limited amount of data , as is the a ). For example , if 75 unique samples are present in the data case in the Examples described here . Also , since the cross set, 75 different calibration models are built resulting in a validation step is repeated several times the dangers ofmodel collection of 75 different sets of significant probes ; bias and overfitting are reduced . [0181 ] e ) select the most significant variables using the [0172 ] Once a calibration model has been built and vali frequency of occurrence criterion in the generated sets of dated , genes exhibiting an expression pattern that is most significant probes in step d ) . For example , a set of probes relevant for describing the desired information in the model appearing in all sets ( 100 % ) are more informative than probes can be selected by techniques described in the prior art for appearing in only 50 % of the generated sets in step d ) . Such a variable selection , as mentioned elsewhere . Variable selec method is performed in Example 1 . tion will help in reducing the final model complexity , provide 0182 ] Once the informative probes for a disease have been a parsimonious model, and thus lead to a reliable model that selected , a final model is made and validated . The two most US 2012 /0295815 A1 Nov . 22 , 2012 14

commonly used ways of validating the model are cross -vali cells in said sample are not disease cells and have not con dation (CV ) and test set validation . In cross- validation , the tacted disease cells , for example the use of a peripheral blood data is divided into k subsets . The model is then trained k sample . times, each time leaving out one of the subsets from training, 10189 ]. The following examples are given by way of illus but using only the omitted subset to compute error criterion , tration only in which the Figures referred to are as follows: RMSEP (Root Mean Square Error of Prediction ). If k equals 0190 ) FIG . 1 shows the accuracy of the prediction model the sample size , this is called “ leave -one -out ” cross - valida across all the PLSR components when probes with a 0 % tion . The idea of leaving one or a few samples out per vali frequency of occurrence are removed from the preprocessed dation segment is valid only in cases where the covariance gene expression data ( 11217 probes ); between the various experiments is zero . Thus, one sample [ 0191 ] FIG . 2 shows the accuracy of the prediction model at- a - time approach can not be justified in situations contain across different PLS components using a 96 assay format in ing replicates since keeping only one of the replicates out will TaqMan LDA analysis ; and introduce a systematic bias to the analysis . The correct [ 0192 ] FIG . 3 shows the efficacy of a random selection of 5 approach in this case will be to leave out all replicates of the or more probes from the Table 5 oligonucleotides and their same samples at a time since that would satisfy assumptions accuracy in correct classification of breast cancer samples . of zero covariance between the CV - segments . EXAMPLE 1 [0183 ] The second approach for model validation is to use a separate test- set for validating the calibration model. This Identification of informative probes and their use for requires running a separate set of experiments to be used as a diagnosis of breast cancer test set . This is the preferred approach given that real test data Materials and Methods are available . Subject Information and Blood Sampling for Microarray [ 0184 ] The final model is then used to identify the cancer , Experiments preferably breast cancer, or a stage thereof in test samples. For this purpose , expression data of selected informative genes is [0193 ] Two hundred blood samples were collected between generated from test samples and then the final model is used 2002 and 2004 at two Norwegian hospitals (Ullevål Univer to determine whether a sample belongs to a diseased or non sity Hospital and Haukeland University Hospital) after writ diseased class, i . e . whether the sample is from an individual ten informed consent under approval from the Regional Ethi cal Committee of Norway (Ref . no . 416 -01151 ) . The subjects with the cancer , preferably breast cancer, or a stage thereof. included were randomly selected from women called in for a [0185 ] Preferably a model for classification purposes is second examination after a first suspect screening mammo generated by using the data relating to the probes identified gram . The samples were collected prior to a clinical exami according to the above described method and / or the probes nation that includes diagnostic mammography and biopsy or described hereinbefore. Such oligonucleotides may be of fine needle aspiration in the case of a positive mammographic considerable length , e . g . if using cDNA (which is encom finding . Cytology revealed whether the findings were of passed within the scope of the term “ oligonucleotide ” ) . The malignant or benign origin . For the subjects with no abnormal identification of such cDNA molecules as useful probes mammographic findings , the standard of truth wasmammog allows the development of shorter oligonucleotides which raphy alone . reflect the specificity of the cDNA molecules but are easier to 101941 From each woman , 2 . 5 ml blood was collected in manufacture and manipulate . Preferably the sample is as PAXgeneTM tubes (PreAnalytiX , Hombrechtikon , Switzer described previously . land ) and left overnight at room temperature before storing at [0186 ] The above described model may then be used to - 80° C . until use . As a result of method development and generate and analyse data of test samples and thus may be testing of various gene expression platforms, only 121 of the used for the diagnostic methods of the invention . In such 200 samples initially collected were included in this study . methods the data generated from the test sample provides the The diagnostic mammograms and histopathology reports gene expression data set and this is normalized and standard revealed that out of these 121 women , 57 had invasive breast ized as described above . This is then fitted to the calibration cancer , 10 had ductal carcinoma in situ (DCIS ) and 54 had no model described above to provide classification . sign ofmalignant disease . Of these latter 54 , 12 had benign [0187 ] To identify genes that are expressed in high or mod findings including fibroadenomas , cysts and some unspeci erate amount among the isolated population for use in meth fied findings ( table 1 ) . ods of the invention , the information about the relative level of [0195 ] Regarding the breast cancer subjects , tumour stage , their transcripts in samples of interest can be generated using grade and other relevant clinical data were recorded ( tables 1 several prior art techniques . Both non -sequence based meth and 2 ). The individuals in the test and control groups were ods , such as differential display or RNA fingerprinting , and balanced in relation to age , menopausal status and previous sequence - based methods such as microarrays ormacroarrays menopausal hormone therapy (table 3 ) . In addition to the 121 can be used for the purpose . Alternatively , specific primer samples , five blood samples were collected from two healthy sequences for highly and moderately expressed genes can be women at multiple time points ( biological replicates ) , three designed and methods such as quantitative RT- PCR can be blood samples from pregnantwomen , and one sample from a used to determine the levels of highly and moderately breast feeding healthy woman were collected , leaving 130 expressed genes . Hence , a skilled practitioner may use a samples from 127 individuals for gene expression analysis variety of techniques which are known in the art for deter ( table 1 ). mining the relative level ofmRNA in a biological sample. [ 0188 ] Especially preferably the sample for the isolation of Study Design mRNA in the above described method is as described previ [019 ] To control for technical variability such as different ously and is preferably not from the site of disease and the microarray production batches , lot variations of reagents and US 2012 /0295815 A1 Nov . 22 , 2012

kits , day to day variations and effects related to different one way ANOVA procedure as described by Tibshirani ( Tib laboratory operators, a strict experimental design was fol shirani et al ., 2002 , supra ). The 26 technical control samples lowed . Samples were randomly divided into batches of 10 , were then excluded . For the biological replicates (multiple containing equal numbers of samples from women with samples from one subject ) , signal intensities were averaged breast cancer and those with no sign of the disease . All for each probes . Thus , 127 arrays, one from each individual samples within each batch were handled together through each experimental step by one operator alone and the opera remained for analysis . Finally , within -array normalization tors were blind to cancer status. Two control samples were was conducted by global mean subtraction . included in each batch following the same experimental pro cedures as the other 10 . These control samples were com Identification of Probes on the Basis of Occurrence Criterion posed of total RNA isolated from one healthy female. The [0200 ] The processed data obtained above was used to iso order of the samples within each batch was randomized . In late the informative probes by: order to correct for any batch variations, we used the batch adjustmentmethod described by Tibshirani ( Tibshirani et al. , [ 0201 ] a ) keeping one unique sample ( including all rep 2002 , PNAS , 99 , p 6567 -6572 ). A total of 13 batches includ etitions of the selected sample ) out per cross validation ing 130 samples and 26 technical controls were thus ana segment; lyzed . [0202 ] b ) building a calibration model ( cross validated ) on the remaining samples using PLSR - DA ; RNA Extraction [0203 ] c) selecting the set of significant genes for the [ 0197 ] PAXgeneTM tubes were thawed overnight in batches model in step b using the Jackknife criterion ; of 12 tubes and total RNA was extracted according to the [0204 ] d ) repeating steps a ) , b ) and c ) until all the unique manufacturer ' s protocol. Total RNA was stored at - 80° C . samples were kept out once (hence , in all 127 different prior to analyses . RNA quality and quantity measures were calibration models were built (after repeating step b ) 127 conducted using the 2100 Bioanalyzer (Agilent Technolo times ) , resulting in 127 different sets of significant gies , California , USA ) and the NanoDrop ND - 1000 spectro probes ( after repeating step c ) 127 times )) ; photometer ( Thermo Scientific , Delaware , USA ) respec [0205 ] e ) selecting significant variables using the fre tively . quency of occurrence criterion amongst the 127 differ Microarray Procedure ent sets of significant probes . [0206 ] In the above method the gene expression data served [ 0198 ] Microarray gene expression studies were conducted as predictors for predicting a dummy- coded response vector. using single channel Applied Biosystems The response vector was given the value - 1 or 1 for each Surveymicroarrays v2 .0 containing 32 ,878 probes represent sample depending on it being a healthy control or a breast ing 29 ,098 genes. From each sample , 500 ng total RNA was cancer sample, respectively . A new gene expression sample amplified and labelled according to the NanoAmp RT- IVT was classified as diseased if the predicted value was larger Labeling Kit Protocol and hybridized onto the array for 16 than zero and as healthy otherwise . hours at 55° C . Following hybridization , slides were manu 10207 ]. Partial Least Squares Regression ( PLSR ) (Nguyen ally washed and prepared according to manufacturers ' rec & Rocke, 2002, Bioinformatics, 18 , p 1625 - 1632 ; Wold : Esti ommendation before image capturing using the AB1700 mation of principal components and related models by itera reader. Identification and quantification of gene expression tive least squares. In Multivariate Analysis . Edited by Krish signals , signal- to - noise ratios and flagging of failed spots naiah PR . New York : Academic Press ; 1966 , p 391 - 420 ) with were conducted using the Applied Biosystems Expression double cross -validation was used to construct and test our System software . Raw data files were exported for further classifier. PLSR with leave - one -out cross - validation (LOO analysis . CV ) was used in combination with Jackknife testing (Gidske haug et al. , 2007 , BMC Bioinformatics, 8 , p 346 ; Wu: Jack Data Analysis knife, bootstrap and other resampling plans in regression [ 0199 ] Data analysis was performed using R ( R Develop analysis . The Annals of Statistics, 1986 , 14 , p 1261 - 1350 ) to ment Core Team . R : A Language and Environment for Sta select significant probes . In more detail , LOO -CV gives the tistical Computing . 2009 ) and tools from the Bioconductor optimal number of components and a set of regression coef project (Gentleman et al. , 2004 , Genome Biol. , 5 , R80 ) , ficients associated with each probe and Jackknife feature adapted to our needs. Data was preprocessed in the following selection was used to select probes with regression coeffi way : data were log 2 transformed while individualmeasure cients different from 0 ( p -value = 0 .05 ) . A PLSR model was ments with signal- to - noise < 3 or flag values > 8191 were setas rebuilt on these significant probes and LOO -CV was again missing . Probes with more than 5 % missing values over all used to select the optimal number of components . Finally , the 156 arrays were excluded . Preprocessing left 156 samples analysis described above was incorporated in an independent and 11217 probes for further analyses . Data were standard loop of LOO -CV in order to test classifier accuracy ( Varma & ized ( i . e . centred and scaled ) and missing values were Simon , 2006 , BMC Bioinformatics , 7 , p 91 ) . imputed with k - nearest neighbours imputation ( Troyanskaya [0208 ] Thus , the selected informative probes based on et al ., 2001, Bioinformatics , 17 , p 520 - 525 ) using k = 10 . Prin occurrence criterion were used to construct a classification cipal components analysis and ANOVA tests for each gene model. The identified informative probes were grouped based revealed that there were large batch -effects present in the on their frequency of occurrence . For example , probes infor data . Similar batch effects have previously been reported for mative in all of the 127 cross validation models were grouped the same type of data (Dumeaux V , et al. , under revision ) . under 100 % , probes informative in only 90 % of the cross Each probe was individually treated for batch effects using a validation models were grouped under 90 % , while probes US 2012 /0295815 A1 Nov . 22 , 2012

appearing as informative in at least one cross validation seg the experiments were performed at a different laboratory and ment were grouped under 0 % . a new sample cohort was used . Diagnostic models were developed using probes that corresponded to 0 % - 100 % Results probes of study 1 ( Example 1 ) and were present in the new [0209 ] Table 4 , lists the number of probes identified based data following preprocessing of the gene expression data on frequency of occurrence criterion and the estimated diag ( study 2 ) . The accuracy was estimated by cross - validation . nostic accuracy of gene expression signatures based on these [0215 ] To further test the effect of different platforms we probes. In order to avoid any selection bias and to obtain analyzed some of the informative probes that were present on unbiased estimates of accuracy, a triple cross validation the customized array that we had developed containing cer approach was used , since the gene selection procedure was tain informative probes identified in study 1 (Example 1 ) . One based on a inner double cross validation routine . The results customized array was based on microarray technology but show that an accuracy of about 75 % is expected from probes was provided by a different platform provider (Codelink , grouped between 0 - 90 % following frequency of occurrence GE) . The other relied on a quantitative real time PCR tech criterion . nology [0210 ] FIG . 1 show that when 0 % probes ( probes thathave [ 0216 ] The Codelink study ( study 3 ) included a new and been identified as informative in at least one of the 127 cross validation models were taken out of the data , the accuracy of independent cohort of breast cancer and non -breast cancer a model based on the remaining data significantly drops samples as compared to our previous experiments ( Table 7A ) . across all the PLSR components (maximum 57 % ), indicating 30 mer oligonucleotides were designed for some of the thatmost of the relevant diagnostic information has now been probes listed in Table 5 . The probes used are provided in Table mined out of this data . 7C which also provides the corresponding gene identified by [0211 ] Table 5 , lists the oligonucleotide sequences of the reference to the ABI 1700 gene identifier (see Table 5 ). identified probes and their gene sequences identified by the [0217 ] In cases when it was difficult to design good primers ABI 1700 number . The probe numbering provided in this from oligonucleotide sequences provided in Table 5 , ABI table denotes the sequence number for the presented probe ID , oligonucleotide sequence and gene namewas used sequences . to identify the relevant transcripts . For some cases multiple oligonucleotides primers were also designed for a specific EXAMPLE 2 transcript. This was to make sure that at least one oligonucle otide would efficiently hybridize to its corresponding tran Verification of Sub - Sets of the Informative Probes script. for Different Samples and on Different Platforms [0218 ] Data preprocessing was mainly as described in [0212 ] Example 1 led to the identification of a set of gene Example 1 . Table 7B shows the estimated accuracy based on probes ( 0 % - 100 % of occurrence ) that can be used to con corresponding 0 % - 100 % probes that were present in our cus struct diagnostically relevant gene expression signatures . tomized Codelink platform for all of studies 1 to 3 . The results However, there could have been questions over the reliability again showed that the different sets of probes (0 % - 100 % ) of identified probes in predicting future samples. It is known retained their diagnostic informational content even when a that variables identified as informative from one particular different microarray platform was used . experiment can be data driven . Apart from depending on the [ 0219 ] In study 4 a TaqMan protocol was used . The Taq sample cohort being used , the platform used to measure the Man system detects PCR products using the 5 ' nuclease activ expression data may also affect data quality . Hence if a set of ity of Taq DNA polymerase on fluorogenic DNA probes gene probes has been identified as informative in one plat during each extension cycle . The Taqman probe (normally 25 form it need not retain diagnostic relevance if another plat form is used for data generation . This is because the platform mer ) is labelled with a fluorescent reporter dye at the 5 ' - end specific noise component may vary among the different and a fluorescent quencher dye at the 3' -end . When the probe platforms. Also if the gene expression changes being mea is intact , the quencher dye reduces the emission intensity of sured are subtle in nature , small technical differences in pro the reporter dye. If the target sequence is present the probe cesses arising for example due to subtle laboratory to labora anneals to the target and is cleaved by the 5 ' nuclease activity tory variations , may also affect the measured value from of Taq DNA polymerase as the primer extension proceeds . As individual gene probes dictating whether they retain or lose the cleavage of the probes separates the reporter dye from the their informational content. quencher dye , the reporter dye fluorescence increases as a [ 0213] Hence, to test the validity of identified probes under function ofPCR cycle number. The greater the initial concen different scenarios we broadened our analysis . To test tration of the target nucleic acid , the sooner a significant whether the diagnostic information of identified probes was increase in fluorescence is observed . retained in an independent experiment performed in a differ [0220 ] The “ TaqMan probe ” consists of a fluorophore ent laboratory using a novel sample cohort , we reanalyzed the covalently attached to the 5 '- end of the oligonucleotide probe data of a study where data was generated using a new sample and a quencher at the 3 '- end .Normally , a 25 -mer oligonucle cohort ( Table 6A , 40 samples , 20 breast cancer, and 20 non otide is preferred but the length can vary . The key point is that breast cancer ) in a different laboratory but using the same ABI the oligonucleotide probe should specifically bind to target platform . sequence . Several different fluorophores ( e . g . 6 - carboxyfluo [0214 ] Table 6B , shows that all the different sets of probes rescein , acronym : FAM , or tetrachlorofluorescin , acronym : ( 0 % - 100 % ) retained their diagnostic information even when TET) and quenchers (e .g . tetramethylrhodamine, acronym : US 2012 /0295815 A1 Nov . 22 , 2012

TAMRA , or dihydrocyclopyrroloindole tripeptide minor groove binder , acronym : MGB ) can be used to attach at the TABLE 2 respective 5 ' and 3 ' - ends ( and these form preferred labels for use in the invention ) . ER and PR status among the 67 breast cancers samples : [0221 ] For TaqMan LDA , DNA was prepared from total RNA isolated from 60 samples ( Table 8A ) . Gene expression Status Number of samples analysis was conducted on ABI Prism 7900HT Fast System using 384 selected assays , including endogenous controls . ER + / PR + Assays with either missing values or an average ct > 30 were removed prior to data analysis ( 166 assays in total) . Using the ER - / PR data of 208 assays in TaqMan LDA ( see Table 8B which lists ER + /PR the 208 assays linked to their gene identifier (ABI 1700 , see ER - / PR + Table 5 ) and function ) we identified a limited number of Unknown assays suitable for a 96 - assay format including assays for normalization and quality control. [0222 ] FIG . 2 shows the accuracy of a model using the 96 TABLE 3 assay format ( across different PLS components ). At the opti mal 5 PLS component, the developed signature correctly Subject demographics predicted the class of49 / 60 samples (82 % ). Again , the results show that diagnostic information was retained in the probes Breast Cancer Healthy derived from Example 1 ( study 1 ) even when a different platform and technology was used to develop a gene expres Demographic information N = 67 N = 60 sion signature . [0223 ] FIG . 3 shows the accuracy of using 5 ormore probes Age randomly selected from Table 5 in correct classification of breast cancer samples . Mean 58 Min 38 TABLE 1 Max Not registered Clinical characteristics of the subjects Menopausal status included in the study ( n = 127 ) Pre -menopausal 14 Diagnosis Number of samples Post Menopausal Unknown 16 Total Breast Cancer 67 Menopausal hormone therapy Pure DCIS 10

a Invasive Ductal Carcinoma (IDC ) Yes 13 Invasive Lobular Carcinoma ( ILC ) No Other invasive Invasive Tubular Carcinoma ( ITC ) Medullary Carcinoma Other /mixed cases TABLE4 Total Non -malignant 63* Diagnostic accuracy of probes by frequency of occurrence Benign changes Fibroadenoma Number of Frequency of informative Fibroadenoma and haematoma probes Accuracy Sensitivity Specificity AUC Cyst occurrence Unspecified findings 0 % 1511 76 . 38 76 . 12 76 . 67 0 . 85 10 % 873 77 . 17 77 . 61 76 . 67 0 .87 No mammographic findings 20 % 786 78. 74 80 .60 76 .67 0 . 88 Controls 30 % 748 80 . 31 82 .09 78. 33 0 .89 Breast feeding 40 % 731 80 . 31 82. 09 78 . 33 0 .89 50 % 707 78. 74 79 . 10 78 . 33 0 . 89 Pregnant 60 % 677 77 . 95 77 . 61 78. 33 0 . 89 Menstrual cycle ( 2 subjects ) 70 % 645 78 . 74 79 . 10 78. 33 0 . 90 130 * 80 % 606 78 . 74 79 . 10 78. 33 0 . 90 Total samples 90 % 538 80 . 31 77 . 61 83 . 33 0 . 90 100 % 282 72 . 44 70 . 15 75 . 00 0 .84 * Data from biological replicates were merged leaving 127 assays for analyses . US 2012 /0295815 A1 Nov . 22 , 2012

AACCTCACTGAAACCTGCTCCGTGCCCGGATGTTGATCATGCTGGTGGCTTGGTTACTGTubiquinol-cytochromecreductase,6.4kDa AACGCATTCATGAATTTCCAGTGTTCAGTAAATAGCAGCTATGTGTGTGCAAAATAAAAGfibroblastgrowthfactorbindingprotein2;FGFBP2 AAGCGGGATCTTGTACTCTCTAAACTGGTCCACAATGTGCATAACCACATCACCAATGACchromosome14openreadingframe93;C14orf93 AAGCGTTCATAATAACTTGCGAATTGGCCCTGATGTTCTAGCATGTGATTACTTCACTCCUBIQUITIN-LIKEPROTEINSUMO/SMT3RELATED AAGGTTTTACTGTCTTAAAGCTGTCTTTCTGAGATSTAATTCCAAGGACTTCTCCACAGCchromosome20openreadingframe108;C20orf108 Genename/symbol AAAACTGCTGTGAACCTCACAGGCAGGTTAAACAAGTATGGAGTGATCAGGCCCAGATTTsimilartoribosomalproteinS15a;unassigned AACAGTCATGATGCTATGGACTCCTACTACGACTACATATGGGATGTTACCATTTTGGAAintegratorcomplexsubunit8;INTS8 AACTGGACCGCGCACGACAGGACCTGCCCTCTAGCCTCGTGGGTCTGTTCCCCAGGGCCCFas(TNFRSF6)bindingfactor1;FBF1 AAGGCTGGACTCCATGACTATATATACATACATCTATCTACATCTGCCTGTGTACACACAGRB2-relatedadaptorprotein2;GRAP2 AAAGTAATCATCGTTCAGGCCCAACCCTTAGGTTTAAAAAGTCAGGTTGTCCATCCCATTcheckpointsuppressor1;CHES1 subunit;UQCR AACGGATCCATATCAGGAAGACAATCTGAAGAGCAGAGATCTCCAAAAACTAAGCATTTC5-azacytidineinduced2;AZI AAGTCCAGGGTTGCTTGGTTTACTGGTTTATAAGAAATCTGAAAGCACCTCTGACATTCCNECAPendocytosisassociated2;NECAP2 AAAAAGAGTTTACGCCTTACGACTACAGCCAGTCAGACTTCAAGGCTTTTGCTGGAAACA0exosomecomponent10;EXOSC10 AAACTAAAAACTAGGAAAGTGTTAACTATCGTTGCCCACCGAATTTGAGGTAGCAAAAAAproteinkinaseD3;PRKD3 AACGCTACAGCGTGGACAAATCTCTCAGCCACCCCTGGTTACAGGAGTACCAGACGTGGCproteinkinaseD2;PRKD2 AAGGGAAAGCTCCCAAAGCATCCTATCATTGTGAAGGCCAAATTCTTCAGAAGAAGAGCA60SRIBOSOMALPROTEINL27A TABLE5 Sequencesidentified AAAAGAGCAACAAAGACTCCAGAACCCACTCTACCTCCTCAATCCCTTGGCCATCTGTGGLOC339483 AAATGATTCCATGGCTCCCTGTAGTACTTCTACAAAGCATCTATCACAATTGTAATTAATUnassigned AACCGCGTGGCTGTTTTTGAACTGCCTGGAACCTAAGACCCTGAATTCTTTTCCCCCCCAMGC16037 AAGGAAACAGGTGACTAGAAGGGCCTGAGGATTACAGTGAACCTGACCATTCAGAACAGAunassigned AAGGATGTCATTGAAGAGTATTTCAAATGCAAGAAATGAAGAAATAAATCTTTGGCTCACRPS12 AAGGCTTCAGAGTAGATATCTCTGCCAATGTGAGGACAGAAGGACTGGTGCGACCCCCCAunassigned

occur.)oligonucleotidesequences

(Freq. of 0 0 0 O 0 0 0 0 O O 0 O O O 0 O 0 0

1100100 100348 100410 101108 101835 102210 102907 103366 103423 103587 103604 103617 103944 105417 105431 105605 105816 105950 105963 105974 106212 106334 No./ABI SEQIDProbeNO.ID Probe 2 w A 5 a 7 v oo o 10 11 12 13 14 15 16 17 18 19 20 21 22 US 2012 /0295815 A1 Nov . 22 , 2012

AATACTGAGAGATTTGGTCAGAATTTGAGGCCAGTTTCCTAGCTCATTGCTAGTCAGGAAactinrelatedprotein2/3complex,subunit5 ACCGATGAAGAGGTTTGAGTAGATGTACAAATCAAGTAATGGTTTGAACACCTTTAATAAkaryopherinalpha4(importin3);KPNA4 ACATCTCCACTGCCCCCAAAGACCTCCGTTGAACATTCTGTATGGAAAAGAGCCCTGGAGchromosome1openreadingframe183;Clorf183 ACCCATCTTCAGTGTCTTACTTGTACTGTATCACATTCCATACCCTCATTTAATTCTTAAtankyrase,TRF1-interactingankyrinrelatedADPribosepolymerase2;TNKS2 ACCCTCCTGCTCAATGGCTACCAGACACTGGAAGACTTCAAAGAGCTGCGAGAAACACACchromosomeXopenreadingframe9;CXorf9 Genename/symbol AATGCCAGTCCTCATGTAACCTCAGGTATCTTCAGCTTGTGGAGAATAAATCTGGTTTAADENN/MADDdomaincontaining3;DENND3 factor);IL16 ACATCAACTACTTCGCCTCCGACGAGCTGACGGTCAAGACCAAGGATGGCATGGTGGAGAHEAT-SHOCKPROTEINBETA1,HSPB1 16kDa;ARPC5 ACAGGCCATGACCTTGAAGTGAAAGTCTTCTGTTGCTATTGTGGGCTCAAATATTTGGTCringfingerprotein141;RNF141 ACAGTTGAAGACCGTTTTGTACTAAGTCTCATTTTGTATACTGGTAAAAACTACATGCTTSFT2domaincontaining1;SFT2D1 ACATTCACGATCTGGACTCGAACTCCTTTGAACTGGACTTACAGTTTTCCGAAGATGAGA3-phosphoinositidedependentproteinkinase AAGTGTCTGGGCCCTGCCTTCACACCAGCCACACGGGCTGCCTGGAGCCAACTCTACGGGneuroglobin;NGB AATCCGACAGTACTGCAATCACTGGCGAAATTTTGCTGACATTGATGATTCCTGGAAAAGgalactosidase,alpha;GLA ACAAGCAGCATTAAGACTGAAGTTGGAATATTCTGTTGACCATAAAACCTTGATATCATTprogesteronereceptormembranecomponent2;PGRMC2 ACAGTCCACTGAATGGGTATAATGAATTGCAGTATATACGTATGATTGCTTTTTAAGTGAneuroplastin;NPTN ACAGTTCCCTTCAGTCTGGTCAGTCCGTTATCTCCCTGCTGAGCTCAGAAGAATTAAAAAinterleukin16(lymphocytechemoattractant ACAGTTTTGCCTGCGAGCTTCCTCCGGTGCTCTTATTGACCTGTTCTGACCCCTGCGCTAOLFACTORYRECEPTORMOR160 1;PDPK1 TABLE5-continued Sequencesidentified AATGAATGATGAAGGAGATCATGACCCAGTTCCTCTACCAAATGTTAATGCAGCAATATTSKP1-RELATED ACAACAGTCACGTTGACCATCAGTGGAGTCCAGGCAGAAGACGAGGCTGACTATTACTGTIGLV3-25 ACAGAGGCCGTGGCAGGGAAACAGGCTTTGCCTTTGTAACCTTTGATGAACATGACTCCAunassigned ACAGCCAGGCATTCACCCAGCAGGTGCACCAGTGCATCGAGTGCTGCCCTGTGCCTCTGGUNCHARACTERIZED

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 O 0 O O 0 O 0 0 0 0 0 0 0 106517 106796 107117 107344 107499 108442 108594 109438 109557 109729 109841 109943 109946 109974 110081 110188 111298 111542 111685 No./ABI SEQIDProbe No.ID Probe 23 24 25 26 27 28 29 30 31 32 33 34 35 36 38 39110417 40 41 42 US 2012 /0295815 A1 Nov . 22 , 2012 20

ACCTGTGATGAAAACATCTGTAACTACTAGCCCACAGAGTGACATGATGAGGGAGCAACTMCM3minichromosomemaintenancedeficient3(S.cerevisiae) ACCGCCTAAAAGTGTATCAGGGTCTTTATTGTGTGGCTATTCGTGATTTCAAACAGGCAGproteasome(prosome,macropain)265subunitnon ACGCTTGTACATGAAGTGTGGAAGGACTCTGCCACAATGTCCCTGGACCCTGAGGAAGAGtransglutaminase3(Epolypeptide,protein-glutamine TGM3glutamyltransferase);gamma- ACGGCGAGGGCGGCTGCATCACTGCGGAGGACTGCCCCTGCGTGCACAATGAGGCCAGCTmucin5AC,oligomericmucus/gel-forming;MUC5AC AGAAGGCTTCCACACTCAAATCTCTAAGTATTTCTCTGAGCGTGGTGATGCAGTGACTAAproteasome(prosome,macropain)activatorsubunit1 AGACCGGCGAAAGAAGGAACGAGTTGAAGCAGTTAATATGGCTGAAGGAATCATTCACGAheatshock70kDaprotein9(mortalin);HSPA9 AGAGTTGTTGCTGCCCGTATTAGGCCACACAGTGGAACCCCATTTATATCATAGCAGAAGmannosidase,alphaclass2Amember2;MAN2A2 associatedprotein;MCM3AP ACGGCTGGAATCCCTCTGTGTGCATGAACTTCTGTGCCGCCTTCCTTAGCTTTGCCCAGAdom-3homologz(C.elegans);DOM3Z AGAAAGGGTAGTTCAAAGAGTCTGTCTTGAGATCTGATTTTTTCCCCCTTTACCTAGCTGTNFreceptor-associatedfactor4;TRAF4 AGAGGCCTCTGTGCCCAGCCTGATTCTCTGCTCCCAGGAGCCAGTGACATGAGGTGCAGApescadillohomolog1,containingBRCTdomain ATPase,6;PSMD phosphopantothenoylcysteinedecarboxylase;PPCDCACTGAGCGACTGGGAAAACTCGGCTCTACATCTCACCCAGAACGGCTTTTAGAAACACCA AGAAAAGTCCTATCAATTACAGAAGCTATACGAACAAAGAAAAATGGTCATGTACCTCAAsortingnexinfamilymember27;SNX27 (PA28alpha);PSME1 ();PES1 Genename/symbol ACCTTTCAGGCCAGACAGGAGCACCTGACCAAAGGCTTCACAGCCGCCCTCACCGCCCGGglycoproteinIX(platelet);GP9 ACCTCATGATATTTTTCGTCAGAGAAAACAGAACACAAGTAGACCACCATCTATGCATGTKIAA1429; ACTTGTCAGGAGTTGAGACTTCCCTGCCGGATTCTATTTTGAAAGTAAATGGTCTTCCCTtestisspecific,14;TSGA14 AGAAGGACAAACCTGAGAAAGAATTAAAAGCCTTTTGTGCTGATCAACTTGATGTCTTTTRNARECOGNITIONRRM/RNPDOMAIN AGATGAAGAGCCGAATACCTGTGGTGCTCCTGGCCTGTGGCTCCTTTAACCCCATCACCAnicotinamidenucleotideadenylyltransferase 3;NMNAT3 TABLE5-continued Sequencesidentified ACTGAGGAAATGAGACAGCACGTGACAAATCCTTAAAGGATACACACATGACAGGAAGGADKFZp5476183 AGACGGAAGCCTGAAAACTCCTCAGACTCCAGCACCTCCCTTTTACAAACTGACGTTTGTunassigned

occur.)oligonucleotideSequences

(Freq. of O O 0 O O 0 0 O O 0 0 O 0 0 O O 0 0 0 111712 111979 112290 112443 112800 112894 112908 113959 113961 114782 115039 115178 115648 115680 116198 116281 116964 117180 117405 No./ABI SEOIDProbe No.ID Probe 43 44 45 46 47 48 49 50 52 53 54 55 56 57 58 59 60 61 US 2012 /0295815 A1 Nov . 22 , 2012

interferonstimulatedexonucleasegene20kDa;ISG20 cofactorofhepatocytenuclearfactor1alpha AGCTTCAAATGAGTTTCAAGGGAATTTTCCCATGTGAAAAAAGGAGAGAACACTGGCATCvitaminKepoxidereductasecomplex,subunit1-likei AGGAGACCGTCAGGCCGCATGTAGACAATGCTGCTAAGAAACAGAACAAAATGCCACCCCDNAsegment,Chr15WayneStateUniversity75 inosinetriphosphatase(nucleosidetriphosphate AGCATTACGGGTTTTCGTTGAGTCTGTTTTAAGGTATGGCTTGCCAGTGAACTTCCAAGCATPase,H+transportinglysosomal42kDavi AGCCAACATCACGTTTTGTTAGCTGTGATTTACCTTTGTCCGTTTAAAAGACTTCACGGAmyotubularinrelatedprotein15;MTMR15 AGCCATGAACATGTTGAGTGAGCATGCTGGAGAATGAGAGACCACATGAAGCAGAAACATmixedlineagekinasedomain-like;MLKL AGCTGGAAGGCCGTGATGCCATCTTCAAGCAGTTTCATTTCAAAGACTTCAACAGGGCCTpterin-4alphacarbinolaminedehydratase/dimerization pseudogene;unassigned AGGAACCTACAGGATTCTAAGGTTTCCTAGGTCACTGAACAACTAATCTTGGTCCCTGAAadaptor-relatedproteincomplex3,mu2 ITPApyrophosphatase); Genename/symbol subunitCl;ATP6Vici AGCCATCACTTCAACATTGTGATAATCCTTCACAGCAAGAAACCGAATAAAATACTAACABTB(POZ)domaincontaining1;BTBD1 expressed;unassigned AGGAGGCCCGCACACCGGTACACTCGTGGACACCTACACACTCCATAGGAGATCCTGGCTGprotein-coupledreceptor172A;GPR172A (TCF1);PCBD1 subunit;AP3M2 AGCACCTCAGCAGCCAGAACAGATATTTCAGTGAAGCTGACAAAATCAAAGTGGCCCAGGIMP(inosinemonophosphate)dehydrogenase2;IMPDH2 AGCCCCCACCGTGGAGACCTCTGACCCTTATGCTGATGATCCTGTACGTCACCCAGCCCTsulfiteoxidase;SUOX unassigned AGGAAAACATGCACTTCGAGATCTGCCCCTGGTCCAGCTACCTCACTGGTGCCTGGAAGCadenosinedeaminase;ADA TABLE5-continued Sequencesidentified AGCAGAGAGAAGCCTGAGCCTGGCCCCAGTTTTTCATTTGTAGAACCTGGGATTCAAACTunassigned AGCCATAATGTTGAACAGAATTGGAGTATTTTCTTTATAATTTCTTGAACAGGCAAATGAunassigned AGCGGATGGTGCCCTGACTCCATCTGGATTCCTTGACGTGTCTCAGACTGGGTCCCTGAGunassigned AGCTGACCTCACTGGCATTAACTGATGTGCCCTACCTGTTCAGCCCCCATCTGGGCCTCGunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 O 0 0 0 o 0 0 0 0 0 0 0 AGCCTCGTGAACGTCCACGGTGCTGTGCTGTACGACAAGTTCATCCGGCCTGAGGGAGAG AGccTTCACCATC???GccTATACAGATGG???????ccCTGccTGTGCTGCTGCT?G?? AGGAGATAAGTTTCCATGCACTTTGGTGGCACAGAAAATTGACCTGCCGGAGTACCAGGG 0 117989 118098 118423 118485 118631 118635 118644 118743 118954 119044 119207 119578 119696 119843 119977 120075 120408 120440 120553 No./ABI SEQIDProbe No.ID Probe 62 63 64 65 66 67 68 69 70 72 73 74 75 76 77 78 79 80 US 2012 /0295815 A1 Nov . 22 , 2012

AGGATGGCAAGGATTAAAAGAATATGATCAAGCATTGGCTGATCTTAAGAAAGCTCAGGGpeptidylprolylisomeraseD(cyclophilin);PPID AGGCCCGTCACAAGATCCAGGCCAAGTATCTGGACCAGATGGAGGACCTGTATGAAGACTarsAarsenitetransporter,ATP-bindinghomolog1 AGGTGTCGCAGGCAGCAGCGGAACTCCTGGCTTTCTGCGAGACGCATGCCAAAGATGACCguaninenucleotidebindingprotein(Gprotein),gamma AGTAGCTGGTGCTGCTCCAGCTGAGGAAGAAAGTGGAAGCAAAGAAAGAAGAATCCGAGGsimilarto60SacidicribosomalproteinPl;unassigned ATAAATTCATGAAAGAAGCCACGACGAATGCACCATTCAGATTGAATAAGAAAGACAGAAserpinpeptidaseinhibitor,cladeB(ovalbumin) ATACAGATGTTTTCCCTTGTGGCAGTCTTCAGCCTCCTCTACCCTACATGATCTGGAGCAalcoholdehydrogenase1A(classI),alpha AGGATTTTGTATCCCCGGCCTACTTGAAGAAGTGGTCAGCTAAAGGAATCCAGGTTGTTGmembraneinteractingproteinofRGS16;unassigned AGGCCTAGATTTGAAATAATGTTTTGTACTTCGGTAAGATGGAAAACTTAGTGATTCACTEF-handdomainfamily,memberAl;EFHA1 AGGTTGGTCTCGGCCCAGTTTCCCATTGATCACTTCACACACATCTTCATCGATGAGGCTMovio,Moloneyleukemiavirus10homolog AGTAAGACTGAAGCAGACATGGAAGAGTATATATGGGAAAATAGCTCATCAGAAAGAAATmitochondrialribosomalprotein835;MRPS35 AGTGTATCGACGGATAACAGAGTTCACATATTCAAACCTGTATCTGTGCAGGCAATGTGGslingshothomolog2(Drosophila);SSH2 ADHIApolypeptide; ATATAACAACATTCAGATGACTCTCCCGAAAACTTACACCATAGCTAATCAATTTCCTCTphenylalanine-tRNAsynthetaselike,beta Genename/symbol (bacterial);ASNA1 AGTATAACAGACACTATACCAAAATACCAAGCAACTGTTTTGAGAACCCAGACTTAAAATexocystcomplexcomponent1;EXOC1 member1;SERPINB1 subunit;FARSLB (mouse);MOV10 AGGCAGCAGCCCAGTCCCCATGTTCTGTCCCCTCACAGGTTCCTACCCCCGGCTTCTTCTsortingnexin26;SNX26 AGGCATTAGGTTTCCCAACTGCTTTGTGCTGATATCAGAACAGCAGAAATTAAATGTGAAaquaporin9;AQP9 AGGCTTATTAGAAGAATGAACTAAGGTGTCTACCATGATTATTTTTCTAAGCTGGTTGGTribosomalproteinL7;RPL7 AGGGACCCTGGTTTGGACTAGACCTTTGGAGGCCGAGTGTTATCCCTGGCTTCTGGAGGGF-boxprotein41;FBX041 8;GNG8 TABLE5-continued Sequencesidentified AGGCTGAGGTCTCCTGGGAATTCTCACCCGCTCTCCTGCTGCTAAGGAAATGACGTCAATUnassigned ATAAGGAATTTGGTAATGATGAAAGCAATTTTGGAGGTGGTGGAAGCTACAATGATTTTGUnassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 O O 0 0 O 0 0 0 0 0 0 0 0 120701 120770 120859 120923 121011 121045 121204 121257 121369 122004 122087 122196 122376 122416 123331 124046 124143 124299 124735 No./ABI SEOIDProbe No.ID Probe 81 82 83 84 85 86 87 08 89 90 91 92 94 95 96 97 98 99 US 2012 /0295815 A1 Nov . 22 , 2012

nGAPdomain-like ATCTGATGACTGCTTTGTGCTGGACAACGGGCTCTGTGGCAAGATCTATATCTGGAAGGGcappingprotein(actinfilament),gelsolin-like;CAPG ATGACGATGAGGATGACACCCCAGTGAAGACGGTTCTGTCCTCCCCATGTGACTCCCGGGfamilywithsequencesimilarity53,memberA;FAM53A ATATTTCACTTTCTCTTTGACTTTAGACCTTTTGAAGTCTGTATAAACTTGTTTTGAAATGRIPandcoiled-coildomaincontaining2;GCC2 ATCAACCCTCCGCCCGACACGAGGCTGGAGCCCAGTGACATTGTCTATCTCATCCGCTCCpotassiumchannel,subfamilyTmember1;KCNT1 ATCACGCGCCCCTGATGGAACTTTTCTGCTGTTGTGAAGTACTTTTATCCATTTGCTTCTmelanomaassociatedantigen(mutated)1;MUM1 ATGACAATGCTTCTCTGTGACTCAAACCAGGAATTTCCAAAGATTTCAAGCCAGGGAGAAsolutecarrierfamily31(coppertransporters),member ATGACTCTGCCCATCCCCATCCTTTCAGCACAACTCCGTTATTGTGGAAGAAATGTCATTolfactoryreceptor,family56subfamilyAmember ATGGAACCTACTGCAAAAAGATTGTCCAAAATGCCTAAGAAAATACTCCTCTGATGCATTsolutecarrierfamily38,member1;SLC38A1 ATGGAATTTGTAAGTTTATGTCTAAAGAGCTTTAGTCCTAGAGGACCTGAGTCTGCTATAadrenergic,beta-2receptorsurface;ADRB2 ATATCCACACAGAAGAATTGATATCAGGTTGATACCCAAAGATCAGTATTACTGTGGTGTpolymerase(DNAdirected),beta;POLB ATGGCTTCATCGACAAGGAAGATTTGCATGATATGCTTGCTTCTCTAGGGAAGAATCCCAmyosinregulatorylightchainMRLC2;unassigned ATGGGATTTGGCCTTTTTGATTAAATTCCTGCTCCCCTGCAAATAAAGCCTTTTTACACAribosomalprotein,largeP2;RPLP2 ATGGGCGCAGAGGCTTTTCCAGTGTGTATAAATCCATGAAAATAAACGCCACCTGCACCCphosphatidylinositoltransferprotein,membrane associated1;PITPNMI Genename/symbol ATGAGATAGTCTTATAAGAATCACGATTTTCTACACCTGTCATTGAGCCAAGAAAGTCCAtryptophanrichbasicprotein;WRB ATGCGCGAGATCGCTCAGGACTTTAAGACCGACCTGCGCTTCCAGAGCTCGGCCGTGATGH3;HIST3H3histonecluster3, (mitofilin);IMMT GARNL1;1 2;SLC31A2 3;OR56A3 ATGCAGAGGGACAAAGGGCTGTGCTACACTTCCCAGTTACATTCTGAAGCTCATAAATGTmalonyl-CoAdecarboxylase;MLYCD ATGGCCGCCGCCAAGCAGTGCAAGGGCATCGTGGACTGCATCGTCCGCATCCCCAAAGATADP,ATPCARRIERPROTEIN ATGTCAAAGGAAATCAGCAGTGATAGATGAAGGGTTCGCAGCGAGAGTCCCGGACTTGTCinnermembraneprotein,mitochondrial TABLE5-continued Sequencesidentified ATATTTACACACAGCACATATATGCACAAAATAGCCTGCCCTTCCCACATGTCTCCCTAAGTPaseactivati ATGCTCAGCGTGAGGCTGGAGCAGCAGCTGACAGTGGCAGTCCTGGCCCAGGGTGACGGTunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 124823 125008 125012 125096 125266 126449 126905 126985 127008 127068 127385 127609 127663 127830 127856 128088 128154 128211 128232 128501 No./ABI SEQIDProbe No.ID Probe 100 101 102 104 105 106 107 108 109 110 111 112 113 115 116 117 118 119 US 2012 /0295815 A1 Nov . 22 , 2012 24

CAAGACGATCCGGGTAAAGTTCCAGGGAGGCCGCGAAGCCAGTGGAATCCTGAAGGGCTTLSM7homolog,U6smallnuclearRNAassociated(S.cerevisiae); ATTTGCCTGATTTAAGTGTCTGAGAAACAAATCTTTGTTCTCTTAGGCTGCAATGGAACAeukaryotictranslationinitiationfactor3,subunit1 CAAATGTCATGAGAAGTTTGATTCAGTAACTTGTGATGGAGGATTCTTTGGTATCTTACTpleckstrinhomologydomaincontaining,familyF(with CAACATCTTTCCTCCTGTGGTCAACATCACATGGCTGAGCAATGGGCAGTCAGTCACAGAmajorhistocompatibilitycomplex,classIIDQalpha CAACTTCTCCGACTCTACCAGCTGATGCTCTTCACCCTGCCAGGGACCCCTGTTTTCAGCsolutecarrierfamily3(activatorsofdibasicandneutral aminoacidtransport),member2;SLC3A2 rprotein2;PHF2 ATTTAAAGAGATCTGTGTACTGTTTACTTCCCACTTCCCAGAATCCCTTGTATCTCCTTTphosphoinositide-3kinase,class2beta FYVEdomain)member2;PLEKHF2 CAACGCGGCCCCCAGCGGGTGTCACCCTGCTCCCTCGTGGGTCGCCTGCGCCCACACCGGsimilartoFSHDregiongene2protein;unassigned ATTCTCTAAAGAATCAGATTGGAGATAAAGAAAAGCTGGGAGGTAAACTTTCCTCTGAAGheatshock70kDaprotein5(glucose-regulatedHSPA5 kDa);78protein, CAAAAAGTGCGTTAGAAACACTTCAAGAAGAAAAGCCTGAGCTGACCGTCGTCTTTGAGCNLRfamily,pyrindomaincontaining3;NLRP3 alpha,35kDa;EIF3S1 ATTTGTAAACCTGTCTCTAATTTGTAATTTTGTAAACCCTGTCTCTCATATTTTGTAAAAlymphocytetransmembraneadaptor1;LAX1 Genename/symbol ATTGAGACACATTACCTGAATAAGCAGGTGAAAGCCATCAAAGAATTGGGTGAGCACGTGferritin,heavypolypeptide1;FTH1 polypeptide;PIK3C2B member13B;KIF13BATTTGTATCATGTAATGAACTAAACCACCTGTAATTTTGTACCGTATGTGTCTTTCCATCkinesinfamily 1;HLA-DQA1 CAACCCGGCCTACATGGATGCCCCGAAGCGGCCCTCTGAGCATTCCCTGGCCTCTCTGGCscotin;unassigned LSM7 TABLE5-continued Sequencesidentified ATGTCTGTGCAGCCTTACACTCTGTCTTTACAGAAGCAAATAGTACACAAAAGATCTATTPHDf ATTTGTTTAAATGTCTACATTCTTTCTAATAAACTGTTGGAAGACTTCTTGGCTGTCCTTUnassigned

occur.)oligonucleotideSequences AIGI

(Freq. of 0 0 O 0 O 0 0 0 0 O O 0 0 0 128603 129530 129671 129999 130267 130323 130335 130358 130560 131059 131259 131334 131413 131551 131688 No./ABI SEQIDProbe No.ID Probe 120 121 122 123 124 125 126 127 128 129 130 131 132 133 US 2012 /0295815 A1 Nov . 22 , 2012 25 .

CAAGCTACAGCGAAAGCTTCCTGTGGAGTCGATCCAGATTGTATTAGAGGAACTGAGGAAvacuolarproteinsorting25homolog(S.cerevisiae); CAATTTGCAAACTTAGTGCTACATCAGACTGTGGAGCGTATTCATGTGGGCAAAAAATACLSM1homolog,U6smallnuclearRNAassociated(S.cerevisiae); regulatorofchromatin,subfamilycmember CAAGAGACTCTTCCAAGGCACTACCAATATGTTATCTCCAGATGCCGCGCAACTGTCTGAfamilywithsequencesimilarity122B;FAM122B CACCTATTGACCATACTACAATGAATGATGATGCCAGGACAGAACTGTACCGCTCTCTTTapoptosisantagonizingtranscriptionfactor;AATF CAGCACTTACCGATCCAGAGCCTCCCGGCCTTCTCCGGTGTCCTGTACCAACTCTTCTATimmunoglobulinmubindingprotein2;IGHMBP2 CAGCCGAGATGCTTTATGGATTGATCCACGCCCGCTACATCCTTACCAACCGTGGCATCGcaseinkinase2,betapolypeptide;CSNK2B CAGCGAACTATGGCTCTTCCTGTAGGACGAGGAATGTTTACCTTGTTTTCGTACCATCCTanaphasepromotingcomplexsubunit1;ANAPC1 CAGTGAAGGTAGAGGAACCCAGATAGAAGAAAATCCTTTGGAAGAAAATATTCTGGCGGGankyrinrepeatandIBRdomaincontaining1;ANKIB1 CATCCCATTTGGTAGTCTAGCTGACTCCATCAGTATTAACCTCCCCGCTCCTCCTAACCTSWI/SNFrelated,matrixassociatedactindependent CATCCTTCAATATAGTGCCTTTAACTTCCCGTGTGAAACCTGATCCTCCACATATTAAAAinterleukin13receptor,alphal;IL13RA1 Genename/symbol CACAAAAGAACGATTTTCAGTGCCCCCAGCAAGGCTGCACCCTCCTTGATCATCACAGGGt-complex10(mouse);TCP10 CAGTCCCTTGTTCCAAAAATTGGAAAATGACCAGATTGAAAGTTTAAGGCAGCGCTTTGGmethionine-tRNAsynthetase;MARS CAGTTGAAAATTAGGTTCTAAGTTGTTCTTGCAGGAATTAGCCTCCCCGTCTCCCAAAACSLIT-ROBORhoGTPaseactivatingprotein 2;SRGAP2 2;SMARCC2 VPS25 LSM CACCATCAACACCTTGGTGGAGAACAAAGAAAGCTCAGCTGGTGGTGACTGCACACGTGG60SRIBOSOMALPROTEINLIA CAGCTACTGCCACTTCGCCTTACATCCCTGCTGACTGCCCAGAGACTCAGAGGAAATAAAseptin4;SEPT4 CAGGCATTCGAGAAGTACCGCCTGCGGGTGAAGAACTTCGGCATCTGGCTGCGCTACAAA60SRIBOSOMALPROTEINL18A CATACAAATCTGATGTTAATGTTTGCTCTTAGAAGTCATACTCCATGGTCTTCAAAGACCF-boxprotein21;FBX021 CATGGAGGGTGTAGAAGAGAAGAAGAAGGAGGTTCCTGCTGTGCCAGAAACCCTTAAGAAribosomalproteinL7;RPL7 TABLE5-continued Sequencesidentified CAATGTACATATCCTAACTTTACCACACATATTCGAACCTACAGCTCACTGCCTGGCCCAunassigned CAGGCATGCAGAAGGCTCTGTGTGCAGCCCCAGACCTGGGTACCTTCGTCACCGTCCTCAunassigned

occur.)oligonucleotideSequences

(Freq. of 0 O 0 0 0 0 O O 0 O O O 0 0 0 0 131715 131936 132553 132642 132648 133356 133626 135425 135704 135807 135917 136418 136420 136996 137061 137326 137501 137907 137986 138526 No./ABI SEQIDProbe No.ID Probe 135 136 137 138 139 140 142 143 144 145 146 147 148 149 150 151 152 153 154 US 2012 /0295815 A1 Nov . 22 , 2012 26

CATGGTTCTTCAGGTCCCCCAGGAATCAGAAACTATCCCTCTTGTGATGAAAGCTGTCTCmajorhistocompatibilitycomplex,class1-related;MR1 CCATGCCAGTCAGGCGGGCTTGCCATGTTCTGTGAATCTCGAGTGAGCGGTGCCACCCGCvacuolarproteinsorting37homologB(S.cerevisiae); CATGTCCCAGGACAGTGTTACTTCTTCTGCATGATGTGTGGTAGACTCCCTTTGCTGGCToxidative-stressresponsive1;OXSR1 CCAAGCTGACTCCTGAGGAAGAAGAGATTTTGAACAAAAAGCGATCTAAAAAAATTCAGAsimilartoribosomalproteinS8;unassigned CCACTGTGGCCTGCTGGGAACTGGGCTGTGGAAAGGTCCGGCCTCGAGTAGGCAAAACCCgbdef:MusmusculusodayneonatethymuscDNA, RIKENfull-lengthenrichedlibrary,clon CCAGAATGTTACAGGATGTAGTAATTACTATAACTTTTTGCGGTGCACGGAACCTGAGGAcarboxypeptidase,vitellogenic-like;CPVL CCATGGAAGTTTGACCCCAACGAGATCAAAGTCATATACCTGAGGTGCACCAGGAGTGAAsimilartoproline-richproteoglycan2;unassigned CCCAATGCTTTCACTCTTATCTACCCTTTGGCACTTATCTTGCTTATCAACATAATAATTchromosome3openreadingframe60;c3orf60 CCCACTTGCACCTCTCCACCTTTGGCACTAGAACTCCTGAGACACCACTTCTCATGCTTCpleiomorphicadenomagene-like2;PLAGL Genename/symbol CCAACACTACCCAGGACTCTTGCTACCTGGTTCCAACTCCAGACAACCACTATGCCAGGCtransmembraneprotein115;TMEM115 CCAACATCTCCAGCTGGATCCCAGGGAAATATCAGCCTTGGGCAACTGCAGTGACCAGGGadeninephosphoribosyltransferase;APRT CCACAAGGCAAAGGGCAAGTGAGGCTGACGTCCGGCCCAAGTGGGCCCAGCCCGGCCCGChistonecluster2,H2aa3;HIST2H2AA3 CCACCTTCACCTTTAGCTTCTTGAAAATGGGCCCCTGCAGAATAAATCTGCCAGTTTTTAvasodilator-stimulatedphosphoprotein;VASP CCATCACTCCATCAAAGTCCCTGGCTATAAGATCTGGATTTTACCCACTCCATCTTCTCTzincfingerprotein142;ZNF142 CCATTTAAAAAACTATGCTGCTGCTCTAGAAACTTTTATAGGAGGACAAAAATTAGTAAGSUPPRESSOROFG2ALLELESKP1 CCAGAGAAAGTCCTCGCTCGTCACCAGCAAGCTTGCGGGTGGCCAAGTTGAATGATGCTGendosulfinealpha;ENSA CCAGTGAACCACTGAGCTCGCACTGTAGCCAGTCCTGTGTGCCCCTGCTGGATTCTGCTThypotheticalproteinFLJ33534 CCATCACCAAAGGTGGAGCAGCCAAAATGAAGTACAATCCCTTTGTGACTTCTGACCGAA60SRIBOSOMALPROTEINL26 VPS37B TABLE5-continued Sequencesidentified CCAAAAAGGCAGCGTTGAAAGGTGTCCACAGCCACATAAAAAAGAAGACCCGCACGTCACunassigned CCACCGCTAGGGTCTCCACAGGCGCCCTCCCTCCGCGCCCTCCCTCCCCCTCGAGCCGCCDKFZP564B147 CCAGCCCCCTGACGGTTTACAGATGCCATGGCAACATCAGGAAGTTACCCTCTATGCTCTunassigned

occur.)oligonucleotideSequences

(Freq. of O O 0 0 0 0 0 0 0 0 0 O O O O O 0 138654 138703 139273 139449 139466 139652 139881 140164 140226 140424 140544 140597 140829 141288 141469 141482 141676 141703 141901 142102 142266 No./ABI SEOIDProbe No.ID Probe 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 174 US 2012 /0295815 A1 Nov . 22 , 2012 27

CCTCCACCAGCATTTCCCTTACTCTGAAGTTCCGGCATTCACATCATTCATGTTTTCTTTnuclearproteinlocalization4homolog(S.cerevisiae); CCCTTAGCAATCCGGCCTCGCAGGCTGTACTTTCATGGTGCTCTCTACCTTCTGGCCCcccelldeath-inducingDFFAlikeeffectorc;CIDEC CCCTTCCAAAAACTACAATATGATGACTGTATCAGGTTAAGATATAGTCTGTGGATGGATB-celltranslocationgene1,antiproliferative;BTG1 CCGGGCGACTGCGAAGTTTGTATTTCTTATCTGGGAAGATTTTACCAGGACCTCAAAGACarginine-rich,mutatedinearlystagetumors;ARMET Meara/KobnerWeber-Cockaynetypes);KRT5 CCCAGTCTTATCTGTGCCTTTACTGCTTTGCGCATCTCAGATGCTAACTTGGTTCTTTTTUDP-Gal:betaglcNAcbeta1,4galactosyltransferaseB4GALT1polypeptide; 1 CCCTTTTTGGCCTGAAGACATTTTAGAATTTCCTAACAGAGTTTACTGTTGTTTAGAAATBCL2/adenovirusE1B19kDainteractingprotein3 CCTCCCGGAAGAGCTTCAAGAGCTAAGAACCTGCTGCAAGTCACTGCCTTCCAAGTGCAGkeratin5(epidermolysisbullosasimplex,Dowling CCTGAAAACCAAGCTTTGATTTAGATTGAGTAAGATTTACCCAGAATGTCAGATTCCTTTpeptidylglycinealpha-amidatingmonooxygenase;PAM CCTGCCAAACAAGCTAATATGGAAACCACATGTAACTTAGCCAGACTATACCTTGTGTAGDEAD(Asp-GluAla)boxpolypeptide3,X Genename/symbol CCCAGGATGACTACTCGGTCCTGTTTGAAGACACCTCCTATGCAGATGGCTATTCCCCTCcoiled-coildomaincontaining101;CCDC101 CCCCGCACACCGTGAGCTACCCGGACAATCTGACCTACCGCGATCTCTACTACTTCCTCTdiacylglycerol0-acyltransferasehomolog1 CCCTTTCATTAGAACTTCAAGCTCTCCAAAGGCTCAGATTATAACTGTTGTCATATTTAT2'-5'oligoadenylatesynthetase, CCTGCCTAACATGCCAGCGCAGCCAACGCTTCCTCAATGATCCCGGGCATTTACTCTGGGribonucleaseP21kDasubunit;RPP21 (mouse);DGAT1 CCCCTGGAAGAGTGATTCTAATCAGGTATTTTCCTACAAAGTTTGGACTGTGTCTTCTTCankyrinrepeatdomain55;ANKRD55 69/71kDa;OAS2 like;BNIP3L linked;DDX3X CCTGGGCATGATGGGCCGAGCCACCTCGGATCCCACTGATTGGCCAGCCGAGCGAGAACCadducin1(alpha);ADDI CCCCACGCCATGCGGCACATCCAGGAGCACTACGGCGGGACTGCCACCTTCTACCTCTCTgalactokinase1;GALK1 CCGGATCCTTCGTGTCCCCACAGCACGTTTCTTGAAGCAGGATAAGTTTGAGTGTCATTTMHCCLASSIIBETACHAIN NPLOC4 TABLE5-continued Sequencesidentified CCGCCTCCATTGCAACATCTTCTACGACTACTCCGGCTACGGTGCCAGCGCGGGCAGGCCUNCHARACTERIZED CCTCCTCACTTGGATAAAAAGCAGATTTGCCTTAGTGCTGCATGTCTGTCTGGGAGAGGGunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 O O 0 0 0 O 0 O 0 0 0 0 0 142421 142487 142757 143032 143181 144028 144049 144135 144168 144479 144646 144765 145597 145675 145726 146019 146289 146331 146661 No./ABI SEQIDProbe No.ID Probe 176 177 178 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 US 2012 /0295815 A1 Nov . 22 , 2012 28

CCTGTACCTGCTCTATTTCAGAGCTTGTGGCTTTGTGTCTCCCCTGCTTTCCCCACGCAGenhancerofmRNAdecapping3homolog(S.cerevisiae); CGACCTCATGAACAAGTTCCTGACCTACTTCCCCGGGAGGAGGATCAGCGCTGAGGACGGcelldivisioncycle2-like1(PITSLREproteins);CDC2L1 CCTGTCCCCTCCACCTTCCCTCACAGTGTGTCTGGTGACAACCGAGTGGCTGTCATCGGCchemokine(C-motif)ligand3like1;CCL3L1 CGCTAGAGGTGAAATTCTTGGACCGGCGCAAGACGGACCAGAGCGAAAGCATTTGCCAAGscavengerreceptorclassF,member2;SCARF2 CGGTGACCTTCTCCACGGAATGCCGGATGCCCGACATCGCCCTGCCCTCCCAGTTTGTGGhydrocephalusinducinghomolog(mouse);HYDIN CGTCTCCTAGGTATTCATTCTGTATTTTGCAAGCCTCAAAACATACGTGAAGTTGGCTTTperoxisomalmembraneprotein3,35kDa(Zellweger CCTGTCCAGCACTGCCTAGTGTTGGAGGGTAGACCAAGGCTGTGCATGATTCACCCCCTCmicrotubuleassociatedserine/threoninekinase CCTTCCATTTGACCTAATTTAACTGGTGAAATTTAAAGTGAATTCATGGGCTCATCTTTAmyeloidcellleukemiasequence1(BCL2 CGCACTGCCACTATAAGGCTCCCACCGTGGTCTTGCACATGACTAAGACGGACCCCTCTTfrizzledhomolog9(Drosophila);FZD9 CGCTTACTACCTTCAGTATAAAAATGTCAGGCCTGATTATCTAAAAGCTATTTGGAATGTsuperoxidedismutase2,mitochondrial;SOD2 CGTGTGTTCTGGCTGTAGACAACATTCTTTATATTGCCAACCTCGGAGATAGTCGGGCAAintegrin-linkedkinaseassociatedserine/threonine phosphatase2C;ILKAP CGAATGTCCTGGCTGATGCTCTCAAAAGGATCAACAATGCAAAAAAGAGAAGCAAACGCCsimilartoribosomalproteinS15a;unassigned syndrome);PXMP3 Genename/symbol related);MCL1 CCTTTCCCTGCATATGCTTCTGATGGTGTCATCTGCTCCTTCCTGTGGCCTCATCCAAACtriosephosphateisomerase1;TPI1 CGCCCTGTGGGTGCACAGCAACCAGCTCTCCATGCAGTGTGTCAAGGATGATGAGCTCTAproline-serinethreoninephosphataseinteracting protein1;PSTPIP1 CGGTGCATCCACGAGGACCTGCTAGGGCTGACCTTCCGGATCTCTCCACACGCCTTCTTCHpaIItinyfragmentslocus9C;unassigned EDC3 3;MAST3 CGGCAGCCGAAGACACTGCGACTCTGGAGACAGCCCAAATATCCTCGGAAGAGCGCTCCC60SRIBOSOMALPROTEINL23A CGGCTCCGTTCGGGCAAGGATAGTTACTGACCGGGAAACTGGGTCCTCCAAAGGGTTTGGnucleolin;NCL CGTACCTTCCCACTGGCCTCAAGTGAGCCAAGAAACACTGCCTGCCCTCTGTCTGTCTTChistonedeacetylase1;HDACI CTAAACATGGTGATATTCTTCCTAATGCTGATGGGACATGGTATCTTCAGGTGATCCTGGCD1cmolecule;CD1C TABLE5-continued Sequencesidentified CGGAGCCACAGACACAGGCGTGAACGGTGACCGAGCCCCCTCTGATGCTCCATGCCCCTGunassigned

occur.)oligonucleotideSequences

(Freq. 0 0 0 0 0 0 CGCACTGCCACTATAAGGCTCCCAC0 0 0 o o o o 0 of 0 0 146768 146806 146814 147139 147521 147811 147922 148434 148685 148950 149133 149320 149466 149642 149923 149934 150024 150233 150510 150670 No./ABI SEQIDProbe No.ID Probe 195 196 198 199 200 202 203 204 205 206 207 208 209 210 212 213 214 US 2012 /0295815 A1 Nov . 22 , 2012

CTACAGACACTGGGCGCCAAGGCCCAGGCACAGACTGACCGAGTGAACCTGCGGACCCTGHLA-Ghistocompatibilityantigen,classI; CTCCTCTTGACTCTCCAGACCTAAAGTGACACCCTTCAGGCACTTCGGGCCCAATTCAGCbiogenesisoflysosome-relatedorganellescomplex1, CTCGAAGCAGAGTTGACGGACACTGCTCCCAAAAGGTCATTACTCAGAATAAATGTATTTproteinphosphatase2,regulatorysubunitBdelta CTCTACTGTCGACTGAAGATCCAAGTGCGAAAGGCAGCTATAACCAGCTATGAGAAATCAFcfragmentofIgE,highaffinityIreceptorfor;gamma CTCTCTACCCTTGCCGTATCTAAGGAGCTGAGGTAATACAGATCCAAGGAGAATTGTATAgeneraltranscriptionfactorIIF,polypeptide2 FCERIGpolypeptide; CTGAAACTTGATGGCTCCGAACACCCTCGAAGCGCGCCACTCGCTTCCCCCATAGCCACCoxytocin,prepro-(neurophysinI);OXT CTGACTCTGAAATCAACCTTACAAATGTGACAGATATCATCAGGGTTCCGGTGTTCAACAtriggeringreceptorexpressedonmyeloidcells CTGAGTGTGTTAAGATGGTATTAATCATGTCGGTGTCATGTCACTAAGTTTAATGCTGCTzincfinger,CCHCdomaincontaining2;ZCCHC2 CTGCCTCTCTGGCCCTCTGAGATATCCCGATGGGCACAAATGGAAGGTGCGCACTTGCCClipidphosphatephosphatase-relatedproteintype Genename/symbol CTCCCTGGCTCTCAGAAGGTATTCCTTTTGTGTACAGTGTGTAAAGTGTAAATCCTTTTTplasminogenactivator,tissue;PLAT subunit3;BLOC1S3 CTGAGGGCGAGAAGATCCGAAAGAAATACCCGGACCGGGTGCCGGTGATAGTAGAAAAGGGABA(A)receptor-associatedprotein;GABARAP isoform;PPP2R2D 30kDa;GTF2F2 CTAGTTTTATGTTTCTTGGGAAAATATCACTTTGTATTCTCTGTCCAGGGCTTCAGATATdrebrin1;DBN1 CTCACCCACAGGTGCCATGTGCACACTCCTGGTTTTCAAACAATTCTCTGGATTTATTTAAXIN1up-regulated1;AXUD1 CTCACCCCTGTCCTCAGAGTGATAAACTAAGTCACATACAGATAAAGCACTGAAAACACCdefensin,beta118;DEFB118 CTCATGTATGTCTACTGGACTCAGCTCAACATGTTCCAGACCTTGAAGTACCTGGCCATCribophorinII;RPN2 CTCGAGAACCTTGTTTAAAAGCAGAAGACTGCAAGATTCCTTCGCCTCAGAAACCAATCTnucleoporin205kDa;NUP205 CTCTTGAGAACTTGGCTCAGGGCTCCTGAGGACCTTTCCCAGCATTACCTTCCCTTCCCTCOMMdomaincontaining4;COMMD4 TREM1;1 2;unassigned TABLE5-continued Sequencesidentified CTCCTTCTTTTCCAGCCCCGGTACCGGACCCTGCAGCCGCAGAGATGTTGATGCCTAAGAunassigned CTGCTGGGATTTGCCCTCCTAGAGTGCCCCTCAGTCCTGGAATACAAGGTGCAGGCTGGAunassigned

occur.)oligonucleotideSequences

(Freq. of O 0 0 0 0 0 0 0 0 O 0 0 0 0 0 150983 151531 151956 151962 152345 152725 152892 153002153002 153036 153055 153297 153454 153812 153914 154230 154419 154456 155029 155318 No./ABI SEQIDProbe No.ID Probe 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 US 2012 /0295815 A1 Nov . 22 , 2012 30

splicingfactor,arginine/serine-rich1(2 CTGGGCGAGCCTCCCGTGCTGCCCGTATCTCGCATGGCCTCCATCCCCTCCATGATCGGGleucinerichrepeatcontaining62;LRRC62 CTTCAGTGGACCGAAATCTGTATTCTGTTTGCGTACTTGTAATATGTATATTAAGAAGCAtightjunctionprotein2(zonaoccludens);TJP2 CTTGAGTCGACTGGAGGCTGCCAGGAATTCAGGATGCATACAGCTGTAATTTAACCCAGAchromosome3openreadingframe18;c3orf18 alternatesplicingfactor);SFRS1 CTTTGGGAAGACCATATCCTCCATACTCCTTGGCCGATTTCTCTTGGAACAACATCACTGchromosome1openreadingframe85;clorf85 Genename/symbol CTGGCTTTCTCAAGAGTATGGATTGACATATTGTGTTATGAATGCACATCTCTCAGATGTdevelopmentanddifferentiationenhancingfactor CTTATTGCTGTGAAGGGCAGACAATGCATGGCTGATCTACTCTGTTACCAATGGCTTTACcaseinkinase1,delta;CSNKID CTTCCCCTGCCGATCCTAAATCAACATCAGGAGAAATGCCGGTGGTTAGCTTCATCAAAAXIAPassociatedfactor-1;unassigned CTTCGCTTCCGAAAAAACTTTCAGGCCCTGTTGGAGGAGCAGAACTTGAGTGTGGCCGAGzincfinger,HITtype1;ZNHITI CTTGCGCTCTACTCTGTAGTTATGTGGATTGCCGAGCAATGACCCTTTTCAATTTCTTATmajorfacilitatorsuperfamilydomaincontaining CTTTGAGATTGTCACTTCTGTACATAAACCACCTTTGTGAGGCTCTTTCTATAAATACATjumonjidomaincontaining2B;JMJD2B CTTTGTTTCTGTCCCCTCCGAGGAGTCATTTTGGTCGACAGGCTCTCAAGGCAACTCCCCkinesinfamilymember3C;KIF3C 1;DDEF1 CTGGTCTCACGTGCCATGCCCACTTGCCACCCCTGTTCGTGAACTTTGCCGACCTCTTTCDKFZp761E198protein;unassigned CTGTGCCTAAGAAGCTGCTCATGATGGCTGGTATCGATGACTGCTACACCTCAGCCCGGGribosomalproteinS2;RPS2 CTTAAGCAATGTATATGCCATGCATTACCATGCACTAATTCAATCACAGGTGTTTCTATCcalcyclinbindingprotein;CACYBP CTTCACACAGCCTTTTGAGCACACATGAGAATGTATACTGGAGAGAAACCCTATAAATATzincfingerprotein14;ZNF14 CTTCATTGAGGGCCTGTACGACATGCACATTCAGCTGCAGAGTGTGCCCTTCCTGCACTGchloridechannel7;CLCN7 CTTCCGCAAACTCACCTACCGCGGCACAGACTTGGACCAGCTGCGGGACGTGTCCTGCGA40SRIBOSOMALPROTEINS15 1;MFSD1 CTTTGACCACCTCAGTGCTCAAGAACAATTTGTGTCCCTCGGGCAGCAACATCATCAGCACD81molecule; CTTTGTAAAGTACTACCATGCTAAGAACGGCCGTGCTTATGTGGAATCCCCAGCCCGGAARUNdomaincontaining1;RUNDC1 CTTTTCCCGAGAGGCTGACAATGTTAAAGACAAACTTTGCAGTAAGCGAACAGATCTTTGtransmembraneprotein4;TMEM4 TABLE5-continued Sequencesidentified

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 O O 0 0 0 0 0 0 0 0 0 CTTGTAATATCCCCTTGCTCCTAACATCTACATTCCCTTCGTGTCTTTGATAAATTGTA 155892 156010 156146 156640 156956 157206 157279 157389 157436 157527 157542 157646 157941 158058 158257 158652 158661 158771 158784 158825 158876 No./ABI SEQIDProbe No.ID Probe 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 US 2012 /0295815 A1 Nov . 22 , 2012 31

GACATACGACTCTATTTCCTACAGTGCGAAACTTGTCATTCTAGATGTTCTGTTGCCAGTeukaryotictranslationinitiationfactor2,subunitbeta GAACAAAATGCAGCTCCTACCCTCCTCGGGCTTTAGTTGTACCTTAATAACAGGAATTTTnuclearreceptorsubfamily3,groupcmemberi GAACGTGCCTCTCTCTTGCTTACAAATGTCTAAGGTCCCCACTGCCTGCTGGAGAGAAAAkillercellimmunoglobulin-likereceptor,twodomains GACCAAGTGCATCTACTGCGGCTTCTGCCAGGAGGCCTGTCCCGTGGATGCCATCGTCGANADHdehydrogenase(ubiquinone)Fe-sprotein8,23kDa(NADH-coenzymeQreductase);NDUFS8 GAAAGCGAGCCCTCAGCTCAGCCCAGGATCCCCAGAATGCCCTTAGGCCCCCAGGAAGGGgonadotropin-releasinghormone2;GNRH2 (glucocorticoidreceptor);NR3C1 longcytoplasmictail,3;KIR2DL3 GAACTTGATCCTGAAAAGCCATCTGATTCACTTTCTGCAAGCCTTGGACTTCAATTAGTTchromosome4openreadingframe27;C4orf27 GACAATAAAAGGTGGCGTTTTTGTACTTTACCTGGATTCCATTGGCTGGTTTTACCACTCchromosome14openreadingframe119;014orf119 GACAGAAAGTAAATCTATGGATATGGTATTTTGTGAATGATCTTTTAAATAAAAGAAAACeukaryotictranslationinitiationfactor4H;EIF4H GACCACCTCCCCCGACTGCCACTCTGGACCTAATAGCTGTTCCTTAGGCCCCACTCCATGCDC42effectorprotein(RhoGTPasebinding) Genename/symbol GAACTACCAGTCCAAGAATCTGTTTAAAATTCAGACTTCAAATAGTGTCAAATAAAAAGTsimilartoribosomalproteins3a;unassigned GAAAGTTGTTGTATACTGTTAACGATTGTCTGCCCATGTCCTGCCTGAAATACCATGATThigh-mobilitygroupnucleosomalbindingdomain 38kDa;EIF2S2 GACCAGTCCCATTCAGATCCGGCTTGGACAGGCACCTGAGATGGTGCCAAAGTGCAGCTGCOMMdomaincontaining5;COMMD5 CTTTTGGGAAGAAATCAGCGGAGAACCTTTATGCTTTATCAGAGGCCCCATCCCCAGAATRNA-BINDINGPROTEINLIN28 CTTTTTTAAGTGTTTTCTATCCGTTATCCATTTCACCCTTGGCCTATCCCTCTCAGATAGzincfingerprotein282;ZNF282 GAAACCATACCGAAGACCTAAGTTCTGTCGAAAAATGAAGTGATGCTCGCGTTTTTAATAnucleolarprotein9;NOLI 2;HMGN2 GAAGCTGGCCCACACCTATCAAAGCCCCCTGCTCTACTGTGACCTGGAGGTGGAAGGCTTcentromereproteinM;CENPM GAAGTCCAAGCAACAGCCTTTGAATGTAACCAATCCTACTAATAAACCAGTTCTGAAGGThydroxymethylbilanesynthase;HMBS GACATTGAGCTTGTTTCAAATTCAGCGGCTTTGATTCAGCAAGCCACAACAGTTAAAAACribosomalproteinL9;RPL9 1;CDC42EP1 TABLE5-continued Sequencesidentified GAAAAAATGTGGGAAGCTTGGATTTTCACTCTCACCTGGCAGTCATGAGGTGCTTCTCTCunassigned GACCCTGTCAACACCCGCGACCCGTCTGCCTGGCCGTAAGTTTGGTATCTGGCTTTTTCTunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 O O 0 0 0 O 0 O O O 0 0 0 0 0 0 0 158926 158974 159001 159269 159460 159559 159749 160054 160068 160171 160712 160973 161646 161818 161988 162105 162160 162185 162244 162427 No./ABI SEQIDProbe No.ID Probe 255 256 257 258 259 260 262 263 264 265 266 267 268 269 270 273 274 US 2012 /0295815 A1 Nov . 22 , 2012

deficiency,complementationgroup2(xeroderma (phosphodiesteraseElduncehomolog, GAGGACTTTTGTCTGGGATTGGTCATCACTCTTCTGTAATGCCCACCTGCCCCTGCCCAGmajorhistocompatibilitycomplex,classIIDQbeta (guaninenucleotideexchangeprotein);EEF1D ERCC2pigmentosum);D GAGAGGCATCTGTCTGCCGAGGACTTCTCAAGGGTATTTGCCATGTCCCCTGAAGAGTTTerythrocytemembraneproteinband4.9 GAGGAGGAGATCACCAAGTTTGAGGAGCACGTGCAGAGTGTCGATATCGCAGCTTTCAACeukaryotictranslationelongationfactoridelta GACGCCTCGCTGGCCATCAAACCCGTATTTGAGCGTTTCCAGTCTGTCATCATCACATCTexcisionrepaircross-complementingrodentrepair Drosophila);PDE4C GAGGTTTCCAAATCAAATATGTTGCAATGGATCCTGTATCCAAATCCAGTCAAGGAAAAAtumornecrosisfactor,alpha-inducedprotein (metargidin);ADAM15 Genename/symbol GACTCTTCGAAGACACCAATCTGTGCGCTATTCACGCTAAACGCGTCACCATCATGCCCAhistonecluster1,H3C;HIST1H3C (dematin);EPB49 GAGATTCACCGGCGAGCCCACTTGTCAGAAAACGAGCTAGAAGCACTAGAGAAGAATGACRNAbindingmotifprotein10;RBM10 GAGCCTCTAGTCCACCCTCTCCAGTGGTCACTCTTGAGTCACATCTGTCACTTAATTATTphosphodiesterase4C,CAMP-specific GAGCCTTGGCCCACACTGAGGCTTAGGCCTCTCTGCCTGGGATGGGCTCCCACCCTCCCCthymidinekinase1,soluble;TK1 GAGTATGCTCGCTATGAGAATGGACACTACTCTTACCGCATCCACCGGTCCCCGCTCTGTTEAdomainfamilymember4;TEAD4 GACTCTGAGCTGTGTTAAGGAGAACAAGGGCAAGGAGACCTCCCTTTGTGCTCCCTCACTsimilartoCG14977-PA;unassigned 2;HLA-DQB2 GACCGCTACCCCCGCAAAGTGACAGCTGCCATGGGCAAGAAGAAGATCGCCAAGAGATCAribosomalproteinL27;RPL27 GACCTCCTGCCCGAACCGCGGATCCTGCAGAAACTCGCTGTGCCCATCATCGACACACCCprotease,serine27;PRSS27 GAGCCCCCTTCAGTCGCAGCCTCACTCTAGGATGAAGCCTGCTGGGAGCGTGAATGACATEnah/Vasp-like;EVL GAGCGCTTCCACCGCTTCCAGCCCACCTATCCGTACCTGCAGCACGAGATCGACCTGCCAtransmembrane,prostateandrogeninduced RNA;TMEPAI TNFAIP6;6 GAGTCCCCTACCATGACTGAAGGCGCCAGAGACTGGCGGTGTCTTAAGACTCCGGGCACCADAMmetallopeptidasedomain15 TABLE5-continued Sequencesidentified GAGAGCGAGCCTGAGCTCTGCTCCCTTGATCTCCTCTGCGTCTCTGCTGGATGGCAGGGCunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 O 0 0 O 0 0 0 0 0 O 0 0 162467 162550 162733 163014 163028 163775 163821 163994 164265 164335 164357 164401 164735 164784 165227 165286 165344 No./ABI SEQIDProbe No.ID Probe 275 276 277 278 279 280 282 283 284 285 286 287 288 289 290 291 US 2012 /0295815 A1 Nov . 22 , 2012 33

(withtransmembranesignal),1;GOLGB1 GATCCAGCAGGTCCTCAAAGACTGTATCGTCCACCTCTGCATCTCCAAGCCCGAACGCCCproteinkinase,CAMP-dependentregulatorytypeI GATGAAGAGAGCATTTTCCACTGAGAAATAGAAGTTTGATTAAAAATCAACCTTGCTTCAactin-relatedprotein10homolog(s.cerevisiae); complement(Cromerbloodgroup);CD55 GAGTCTGCTTTCTTCTACTGCCCTGAGCCTGAACGCTTCTGCTTAATCTGAGAATCACATgolgiautoantigen,golginsubfamilybmacrogolgin GAGTTGTCTTTGTACTCTTGAGTTGTACCTTATTCTTCCACTTGGCCTGAGTTTTTATAAcoenzymeQ10homologA(S.cerevisiae);COQ10A GATAGCTGTCCTGTTAGAATCAGAAATCGGTGTGTTATGACGTCCCGTCCGCGTGGTGTGmitochondrialribosomalproteinS14;MRPS14 GATGTTTGAGTCCGAGTCCTAGGCCACTCGCTGCCCCTACGCCTGCCCCGGTGCCCGGCTtroponinItype2(skeletal,fast);TNNI2 GCAATGGATTCAAGTTCGAAATATGGCAACTTTGAAAGATATCACCAGGAGACTAAAGTCATPsynthase,H+transportingmitochondrialF1complex,gammapolypeptide1;ATP5C1 Genename/symbol GCAAAATTGCTAAAGAGAGATGAACCACATTATAAAGTAATCTTTGGCTGTAAGGCATTTCD55molecule,decayacceleratingfactorfor beta;PRKARIB GATGATGCTCTCCCGCCACTGAGGCTCCAGGAGGGAATATCTGTTGCCCCTGCGGCCCCAcalciumbindingprotein4;CABP4 GATGCAGATGACTTTGGCCTACAGTTCCCGCTGGACCTGGATGTGAGGGTGAAGGCTGTGphospholipidscramblase3;PLSCR3 GAGTTTATAACTATAATCACCTAATGCCCACAAGGTACTCTGTGGATATCCCCTTGAACA60SRIBOSOMALPROTEINL27E GATCCCTTGTTTTCCTGTCAGTTGGACCCCTCACCTGGCCTCCAGGGAAGAATGCAGAGAapelin,AGTRL1ligand;APLN ACTR10 GATGCGTGGGCTGACATCTGCAGGCCGAAAGAGCCGTGGCCTTGGAAAGGGCCATAAGTTribosomalproteinL15;RPL15 GATTATATTGGTTCTGCCTCTGGCATGCTGGTAGACTAGGGCCATCCTAACTTATTATTTIQmotifcontainingBl;IQCB1 GATTCCCATACACTGGACAGCCAAGTTACCAGCCAAGTGGTCAGTCTCAGAGTCCTCCCCdipeptidase2;DPEP2 GCAACCGAATTCCAGTTTAGAGGCAGATGTGGTCGTGGACGTGGTCAGCCACCTCAATAAribosomalproteinS10;RPS10 GCAAGAACAAGTACCGCCCCGACCTGCGCATGGCAGCCATCCGCAGGGCCAGCGCCATCCribosomalproteinL28;RPL28 TABLE5-continued Sequencesidentified GAGTCCTATGTGGGATGAATAGCTTCAGCCTTTGCGCTTGCACCTCTTTGCTGTCCACTCunassigned GATCCAACTGCACCCATGGGAAATCTGAACTTCCACTTTCTTTGAGCTTGTCTTTGGTTGHSPC157 GCAATCAAGTGGGCTTCATCAATTTAATTTCTTCTCTTTGAGTAAATGAAGATTCAGACTDKFZp313A2432

occur.)oligonucleotideSequences

(Freq. of 0 0 0 O O O O 0 0 0 O O O O 0 O O 0 0 165355 165397 165594 165595 165796 165993 166010 166052 166256 166394 166429 166502 166813 166860 166918 167208 167373 167428 167622 167654 No./ABI SEQIDProbe No.ID Probe 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 308 309 310 311 US 2012 /0295815 A1 Nov . 22 , 2012 34

ITIH4glycoprotein);sensitive GCCACAAGCCTGAATTTCTCAGTGTTGGTAAGTTTCTTTACCTACCCTCACTATATATTAIKAROSfamilyzincfinger1(Ikaros);IKZF1 GCCGCCCAGAAAATGCCATCATCTATAACAACAATGAGGACTTCCAGGTCGGACAAGCCAtransketolase(Wernicke-Korsakoffsyndrome);TKT GCGCTAACAGAGCTGGAGATTCTAGATATTTCTTTTAATCTGCTGAGAAACATCGAAGGGproteinphosphatase1,regulatorysubunit7;PPP1R7 GCACCAGCACCTTGGAAGCACCAATAAAGAGGATGCCCACGTGGCCCCAGCAATCAGAAGinter-alpha(globulin)inhibitorH4plasmaKallikrein GCAGAAGCATCGGTGCTGATACTCTTCAATAAAATCGACCTACCCTGTTACATGTCCACGADP-ribosylationfactorlike16;ARL16 GCATGACTATTCAGATGGCTACTGAGTTATCAGTGGCCATTTATTAGCATCATATTTATTWDrepeatandsocsbox-containing2;WSB2 GCATGCCTGGAAGTTGTCATGTTTGTGCCACGTTTCAGTTCAGTTCTGAAGTGTTATTAAvoltage-dependentanionchannel3;VDAC3 GCATTGGAAGGCATAAGACCTACCTGTGCTACGAAGTGGAGCGCCTGGACAATGGCACCTapolipoproteinBMRNAeditingenzyme,catalytic APOBEC3Alike3A;polypeptide- GCCCTAGTGTGTAAATGACTTGGATCTCCCTCCTGGCAGACTGTGACCCTCAGCACAGGGchromosome22openreadingframe29;C22orf Genename/symbol GCATGTGAGTGCCCCCAGAACTGTCCTGGCTCCTTCCGTATTAAACGCATTTGCATTTTGubiquitinassociatedprotein1;UBAP1 GCCCTACATATGTGAACATTGTGGCAGAGCTTTTAACCAATCCTCGAACCTTACTAAACAzincfingerprotein724pseudogene;ZNF724P GCGGCCAGTTTCAGGTCCAGTGAGCATGAGAATGCCTATGAGAATGTGCCCGAGGAGGAAPDZK1interactingprotein1;PDZK1IP1 GCAGGAACCTGCCAGTTCTCCTTGGTGCAAAAATCTGACCCTCGGCTGCCCTGCAAAGGGPROSTATESECRETEDSEMINALPLASMA PROTEINPRECURSOR GCAGTGTGAACTCTTTATTCACTCCCAGCCTGTCCTGTGGCCTGTCCCACTGTGTGCACTtubulin,beta2C;TUBB2C GCCAACCATGGTGAACTTGGGTCTGTCCCGGGTGGACGACGCCGTGGCTGCCAAGCACCCtransmembraneprotein141;TMEM141 GOCCAGTCTTCTATCCCCCACCTAAAAAGACCAAGCATTGATGCCCAAGTTTTGGAAATAribonucleaseT2;RNASET2 GCCGGAGAAACTGCCCAGCAGATCTGTGAGGACCTCAGGTTGTGTATACCTTCTACAGGTgranulysin;GNLY GCCTATTGGTATCTGTGTATATTTACGTTAAACACAATTATGTTACCTAAGCCTCTGGTGsynaptotagmin-like3;SYTL3 TABLE5-continued Sequencesidentified GCCCGACGTGACCTCCACCCCTAGTGCCTGTGATCTGACTCTGCCCGACGTGACCTCCACunassigned GCCGCCCTGGCTGTGTGTGAAACATTTGGAGATACCTGGAGTACGGACAGTCACCTCTGAunassigned GCGCTGCCATCATCCAGCCACTGCAGTCGCCGCTGCCGCGCCCCTGAGCCCGGGTCCCTGunassigned

occur.)oligonucleotideSequences

(Freq. of O 0 O O O O O 0 o 0 0 0 0 0 0 0 O 0 167861 168184 168631 168915 169187 169221 169282 169382 169512 169647 170287 170453 170536 170551 170781 170788 170844 171063 171985 172014 172117 No./ABI SEQIDProbe No.ID Probe 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 US 2012 /0295815 A1 Nov . 22 , 2012 35

GCTAGAAATGACTCCTGAACTTGGACATGTCTACACCTGCCTTGTCGATCACTCCAGCCTmajorhistocompatibilitycomplex,classIIDO GCTGTACAGTTCAGTAGAGTGGTCACTTTCACTGCAGTATACATTTATCTACACATTATAnudix(nucleosidediphosphatelinkedmoietyX)-type SSR4deltaprotein);associated GCTAAGCTGAATAATGACAAAGTTGAAAGGACCAATACAGCCCCTTTTATAAGGATTTTGCCR4-NOTtranscriptioncomplex,subunit1;CNOT1 GCTTCTACCCTCATACCCACAATATGGATGGGTTCTTCATTGCCAAGTTCAAGAAATTTTnucleolarprotein1,120kDa;NOL1 GGAAAGCCCTGGAGGGAATCACATGTGTACTTTTTCATGAAGCTTTTTGCAAAGCACATCcoiled-coildomaincontaining69;CCDC69 GGAATAACGAGGACATTTCCATCATCCCGCCTCTGTTTACAGTCAGCGTGGACCATCGGGsignalsequencereceptor,delta(translocon GGAGCTACTGAAGGTCTCCAAGGACAAACAGGCCCTCAAATTTATCAAGAAAAGGGTGGGsimilartoribosomalproteinL36;unassigned GGCAGCGTGGATCTGCCCACACATAGGCTACTGGAATAGTTTAACCCAGCAACTTTCCTTzincfinger,AN1-typedomain3;ZFAND3 Genename/symbol GCGGGCCTCCGTGGAGCTCCTGGATGAGATGAAGTTCTCGCTGGAGAAGCTGCACCAAGGGRAMdomaincontaining1A;GRAMD1A beta;HLA-DOB GCTGAAGGTACAAGAAGAAATGCTTAAGGAAGAATTTCAAAAGAAATCTGAGCAGTTAAAguanylatebindingprotein4;GBP4 protein;unassigned motif3;NUDT3 GGAACCAGGGCATCGAGGCTGCGATGGACTGGCTGATGGAGCACGAAGACGACCCCGATGSAPKsubstrateprotein1;unassigned GGAATGGGCGAGACATTGCTGCAAAGAAGTCAAGCTTTTTTCAGACAAAAGGTGTGAGGGthymocytenuclearprotein1;THYN1 GGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCIMMUNOGLOBULINLAMBDACHAINCREGION GCTGCCTCAAGTCCTGGAAGCCAAATCACAAAGACTATTACAACTGCTCTGCCATGGTAAp53-associatedparkinlikecytoplasmic GCTGTGCTCTTTTCAAGCCATGTCCGCAAGGTGAACCGCTTCCACAAGATCCGGAACCGGmyosinIG;MYO1G GGAGACCTGAAGTTGCTCTTTGAGTACCTGACCCTATTTGGCATTGATGACAAAATCTCChistidyl-tRNAsynthetase;HARS GGAGATCTATCTCTTCTCTCTGCCCATTAAGGAATCAGAGATCATTGACTTTTTCCTGGGribosomalproteinS2;RPS2 GGATGGGTCCAACGTGGTCTTTAAACTTCTGGGTCCGGTGCTAGTCAAACAGGAGCTGGGprefoldinsubunit6;PFDN6 TABLE5-continued Sequencesidentified GCGGCGGCAACGCGGTGGCCTGTCCGGTGTGCCGCGCGCCCACGCGCCTGGCCCCCCGCCUNCHARACTERIZED GGAGCTGTCAAGCCCTGCATTGCCTCCCCCTGGACGTCTCATTATGGGAGAAAATGAAGCunassigned GCCGCCCTGGCTGTGTGTGAAACATTTGGAGATACCTGGAGTACGGACAGTCACCTCTGAunassigned

occur.)oligonucleotideSequences

(Freq. of 0 O O 0 0 0 0 0 0 0 0 0 O O O O O O 0 0 172139 172191 172470 172619 173310 173605 173972 174085 174420 174881 175030 175376 175469 176248 176372 176535 176569 176998 177291 177583 177856 No./ABI SEQIDProbe No.ID Probe 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 US 2012 /0295815 A1 Nov . 22 , 2012 36

neuroblastomaderived(avian);MYCN GGGAGGTACAATAAGAACATGTCAGAAGTTCCTAATTCAGTACAACAGGAGACAGCTGTTprocessingofprecursor5,ribonucleaseP/MRP GGGCCAAGAAGCAGGAAGCCTTGCGGAGAGTGACGGAGAATCTGGCCAGCCTCACCCCCADiGeorgesyndromecriticalregiongene14;DGCR14 T-CELLRECEPTORBETACHAINVREGIONC5 GGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGGCACTGTATTTAACTAACTTTodz,oddOz/ten-mhomolog3(Drosophila);ODZ3 subunit(S.cerevisiae);POP5 homologF(avian);MAFF GTAAGGATTGAAAGGCTTGTAATCCAAAGTTACTTTGTACAGACCTTGAAGATTGAAAAAchromosome1openreadingframe41;Clorf41 symbolnameGene/ GGCCACTGAGTATGTCCACTCCCTCCAGGCCGAGGAGCACCAGCTTTTGCTGGAAAAGGAmyelocytomatosisV-mycviralrelatedoncogene, GGGTACCTCTGCAACAGGAAATCCATGACCCAGCCCTTCACCAGTGCTTCAGCCACCACCLY6/PLAURdomaincontaining5;LYPD5 subunit;unassigned GGTGAAAGAATTAATGAACTCCAGTACCTGAAAGTGAAAGATTTGATTTTGTTTCCATCTthioredoxindomaincontaining13;TXNDC13 GGTGCATTTCAGAAAGGATGGAGAACATTTATTATGTGTGAAAGCATCCTCTTCCGGTTTubiquitinspecificpeptidase48;USP48 GGTGTAATTGAAGGGTGTGAAATGCTTTGTCAATCATTTGTCACATTTATCCAGTTTGGGYME1-like1(s.cerevisiae);YME1L1 GGCCCATCAAAAGCCTTTATCCCTTGACATTTATCCAGGTGAAACAGCATTATGGGTTTGgalactosidase,beta1;GLB1 GGCCTCATTCCTTTACCACTCCCACACCTGGAAAGCATATACTATATTACAAAATGACATMOESIN/EZRINRADIXIN GGGACAGTTTGGTATTAAAACACTTAAATATAGATCCGGTGGTATGGATGAGAAAACAATCD47molecule; GGGACCGTCCTGCTGAGAAATTGCACTGAAGAGATGCCCCCACCTCTGGTTGGGCCTGGGv-mafmusculoaponeuroticfibrosarcomaoncogene GGGTGGAGGGTATGAAAATGACTGCAGCATAGCACGACTGAACAAGCGCAGTTTCTTCATpyruvatedehydrogenasephosphataseregulatory GGTACCAGTGTTACTATGGGTATCCGCCGCTGACCTACCTGGAGTACCCCATCCTCATCGPQlooprepeatcontaining3;POLC3 GGTCGTATTGAACACCTGGTAACCAAGCCTGCTTTTAACTCTGGTAAAGTGGATATTGTCGLYCERALDEHYDE3-PHOSPHATE DEHYDROGENASE GGTGGCCCATCTGTTCAGGGTGGCTGCACGATTTATGGAAAACAAGATGTCTGCCAACAAGEMinteractingprotein;GMIP TABLE5-continued Sequencesidentified GGCAGCTTGCAGTCCGTGGTGATGAAGAGTTGGATTCTCTTATCAAGGCTACCACAGCTGHISTONEH2A GGGTTCCCCTGCTTCCAACCTCCATTGCACTGCTTCCCCTAAGACTGTGACCTCCTGGAALOC338799

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 O GGTATCACTGACCAAGGAGAAGTCCCCAATGGCTACAATGTCTCCAGATCAACCACAGAG 0 0 177865 178216 178379 178628 178643 179899 179935 180173 180500 180917 181160 181239 181391 181496 181810 181937 182125 182284 182375 183023 No./ABI SEOIDProbe No.ID Probe 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 US 2012 /0295815 A1 Nov . 22 , 2012

GTGGTGCGGAGCTCCTGTTTGACGGTATTAAGAAACATCGAGTCACTTTGCCTGGACAGGubiquitinrelatedmodifierihomolog(S.cerevisiae); GTTCTCGGAGCCATTTGTACATTTCATCACTCAGTGTATGCGAAAACAGCCAAAAGAAAGmitogen-activatedproteinkinase5;MAP2K5 GTTCTTCGTCACTTAATGTTGGTTCCAGTCCTTCAACTGTTCATATCTACTTTATAACATenhancerofrudimentaryhomolog(Drosophila);ERH GTAGGCGGGTTATCTGCGAACACAGTAGTGGAAGATGTAAAGCAATATTTCGAGCAGTTTmusashihomolog2(Drosophila);MSI2 GTCCGTCTAGCTCACGGGCCCCTCCAGTGGAATGGGTCTTTTCGGTGGAGATAAAAGTTGmannosidase,alphaclass1Bmemberl;MAN1B1 GTGAAATGTTTGTCACTCTTACTGCACAGACTTATCTGCAATCAAACTGGTTAGTTTTTTrecombiningbindingproteinsuppressorofhairless GTGCACTTCCTGGTCATTCCTAAGAAGCCCATTCCTCGGATTAGCCAGGCTGAAGAAGAAhistidinetriadnucleotidebindingprotein2;HINT2 GTGGAGAAAGTTTACCCACCAGTGCCTGAGCAGCTACAGCTCCGAATTGCTTTTTGGAGCspermidine/spermineNl-acetyltransferase1;SAT1 GTGTTCATCTGAGCATAACTGTACTAAATCCTTTTTCCATATCAGTATAATAAAGGAGTGphosphoglyceratemutase1(brain);PGAM1 GTTACTAAAACGTGAATCCTAAAATGAGAAGCAGTTCCTGGGACCAGATTGAAATGAATTSEC11homologc(S.cerevisiae);SEC11C GTTCCCAACTGTTGGCCAGAATGAATTCTTCGAAAAATATAGGTGGTTTCCAGGGAATTTCMT1Aduplicatedregiontranscript4;CDRT4 GTTCTTAAGTTTTTTGCTGCAGGAACCCATTTAGGTGGCAACAACCTTGACTTCAAAATGsimilartolamininreceptor1(ribosomalprotein Genename/symbol (Drosophila);RBPSUH GTGTCTGCCGATTCCCGCATTGCAGAACTTCTCACAGAGCTCCATCAGCTGATCAAACAAcoiled-coildomaincontaining101;CCDC101 GTTCAAAGGATCGATGGACCGTAAATAAGCTGCCATTAACACATCTGGTTACTGCTGTAARNAbindingmotifprotein22;RBM22 GTATTTATTGGCTTCAAGGCCCACCTCTCTGTACTCTGGGCTCTAAAGTTGGAGGTCAGGdynactin3(p22);DCTN3 GTCCCTCCTGGTGTCACCCCAGAGCCACACATGGGCATCTATGGGAGAGTGTCAACCAGAT-cellleukemiahomeobox1;TLX1 GTTACAACCGCAATCTCTCCAAGACGGAGTTCCTAAGCTTCATGAATACAGAGCTGGCTG$100CALCIUM-BINDINGPROTEINA11 SA);unassigned GTTGATTCACCTAACTCATTATTTTGCTTTATTAAAAGTCTTCCTTCACCACCGAGATATRassuppressorprotein1;RSU1 GTCTTCCTCGGGCAGCAGGTGGGAAGTGGGAGCCGGAGCGGCAGCTGGCAGCGTTCTCTCribonucleaseT2;RNASET2 URM1 GTTCATAAGAAGGCAACAAATTCTTCTCCTCTACAGAAGGATTTTGCAAACAATTTGGCAFAMILYNOTNAMED TABLE5-continued Sequencesidentified GTCATCAAGGTGTTCAGTGACATGAAAGTGTGCAAGTCTTCAACACTAGAAAAGGTGAAGCFLP1

occur.)oligonucleotideSequences

(Freq. of O O 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 183441 183747 184125 184429 184488 185093 185214 185730 186249 186765 186980 187172 187317 187369 187518 187600 187667 187829 187871 187881 187987 No./ABI SEQIDProbe No.ID Probe 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 US 2012 /0295815 A1 Nov . 22 , 2012 38

TACATTAGATGGTGTGTCCCGGAAGAAACTTCACCTGAGAACTTTTGAACTGAGGAAAGAsolutecarrierfamily4(anionexchanger),member1 TAAAGTTGGAAAGTCCCCGTCCCCCAGAACCTCAAGTCTAGAAACCAGTATGGAAGGGAGpotassiuminwardly-rectifyingchannel,subfamilyJ TACCTAGTCCCCAGCCTGCTCCCTAGCCAGAGGCTCTAATGTACAATAAAGCAATGTGGTcytochromeP450,family2subfamilyDpolypeptide TAGACCTGATGTGTTAGATACTGCTTTGTTACGACCTGGAAGATTAGATAAGATCATCTAspermatogenesisassociated5-like1;SPATA5L1 containing5(S.cerevisiae);DCUN105 TAAAAAGGCACAACTCAAATCTCAGAGACACTAAACAACAGGATCACTAGGCCTGCCAACchromosome12openreadingframe46;C12orf46 adaptorprotein;SLC4A1AP TAGATCAACTTTTAACTCAGAGTCCTGGTGACTATATCCCCATATCCTATGAACAGATATchromosome10openreadingframe46;ci0orf46 TATGACCCCTGGACTAACCCCAGCCAATTCCCAGGCCTCAAAAGCCACTCCCAAGCTAGATreacherCollins-Franceschettisyndrome1;TCOF1 TATGTGAAGAAAATGCAAACCTTTCAATTCCCACGTGTATACAAGCTAATGTGATGAGGGDCN1,defectiveincullinneddylation1domain TCACATAACTGTAATATTTGGTTGCTCAGCATAAGTGATGGAAGCAAACACTAATTTCTAtumornecrosisfactor,alpha-inducedprotein1 TAAAACCTTGTTTAGTAAAGCCAAGTCATACTATAGAAGAACACATTCAGATGCCAGTGARhoGTPaseactivatingprotein5;ARHGAP5 TAAAGCCAAAGCTGTTACAGAGATGAACATCTTTTGTCAAACCATTAAGAGTTAGAAAGAchitobiase,di-Nacetyl;CTBS TACTATTGGTGTAGAGTTCGGTGCTCGAATGATAACTATTGATGGGAAACAGATAAAACTRAB2,memberRASoncogenefamily; (endothelial);TNFAIP1 Genename/symbol UQCRHprotein; member9;KCNJO TACAGCCCCTACCTTCAGAGAGCACCTGGCCTGCAGCTCATCCAAACCTGAGTCTCCTCTPQlooprepeatcontaining2;POLC2 TACATTACCCATCTCCTCTTTTGCCTCTGAGAAAGAGTATATAAGCTTCTGTACCCCACThistonecluster1,H2bk;HIST1H2BK TATAAACTACTTATAAAGGCCCTTCAGTTATCTGAACCTGGCAAAGAAATTCACTGATTTtransmembraneprotein126A;TMEM126A TATCACTTTGGCTGGACCCACTAATGCCATCTTCAAAGCCTTTGCTATGATCATTGACAApoly(rc)bindingprotein2;PCBP2 CYP2D6;6 TACTTCTTCCATGAATTGGCCAAGGAGAAGCGCAAGGGTGTTGAGCGTCTCCTGAAGATGLIGHTCHAINFERRITIN TAGGAAGTATTAAAACTGTGAAGCTTTCTCAGTGCACTTTGAACCTGGAAAACAATCCCALIMdomainkinase1;LIMK1 TABLE5-continued Sequencesidentified GTTTTGGATGTACCATTTGTTTCTTATTTGTGTAACTGTAAGTTCACATCAACCTCATGGubiqu

occur.)oligonucleotideSequences

(Freq. of 0 0 O 0 0 O O O 0 0 0 0 O 0 0 188616 188678 188703 188846 189918 190073 190074 190302 190571 190803 190949 191074 191350 191714 191970 192246 192503 193530 No./ABI SEQIDProbe No.ID Probe 395 396 397 398 399188901 400 401 402 403 404 405 406 407 408 409 410 411 412 413 US 2012 /0295815 A1 Nov . 22 , 2012 39

TCCCTGCCCTCACCTGCAAATGAGTTAAAGAAGAGGCGTGGGAATCCAGGCAGTGGTTTTMAP/microtubuleaffinity-regulatingkinase4;MARK4 TCCCTTGTTTAGAACACGAATTTCCATTTACCTGGTGGGAACACGAAACAGGAGTCTCTTgolgiautoantigen,golginsubfamilya1;GOLGA1 associatedserineesterase1);GZMB TCGAGATAAGAGAGCAGATGTTGGAGAATTCTTCTAGATTTTCAGAACTTGAAGACTATTinterferon-relateddevelopmentalregulator1;IFRDI TCATACGTTGTCCAGCTGTAAGTTCATTTGAGTAGCAGACCTAACAAATATTTGAGGTCAMof4familyassociatedprotein1;MRFAP1 TCATGGACAGACTGGCCTTCTTAGCTGTACTATAAATTTGTGAGTGAAGTTAGAGCCCAGchromosome1openreadingframe142;Clorf142 TCATGTGCTGGTACCAATAGGACAGGAAGATTTTAATCAGCTTTACTATCTATGTTTTTTpyridoxamine5'-phosphateoxidase;PNPO TCATTTATATCCCCACCGCAATACTGTGGATTATCCCCCAGAAAGCTGTTCGTTGGATTCYipidomainfamily,member1;YIPF1 TCCAACATTGGGAATAATTATGTATCCTGGTACCAGCAGCTCCCAGGAACAGCCCCCAAAhypotheticalproteinsimilartoKIAA0187gene TCCATTCTTTTGAGCAGGTTAAAGCCATTCACATCCATTCTGACATGTTCTCAGTTCAAAacyl-CoAsynthetaselongchainfamilymember TCCGTGGGCATCATGTTGACCGAGCTGGAGAAAGCCTTGAACTCTATCATCGACGTCTACS100calciumbindingproteinA8;S100A8 TCGAAAGTGCGAATCTGACTTACGCCATTATTACGACAGTACCATTGAGTTGTGCGTGGGgranzymeB(2,cytotoxicT-lymphocyte Genename/symbol product;unassigned TCCAGCCTCTACCATCACCTGCATGTGGCCGACACACGCTTCGACATGGTCCAGCTCATCv-rafmurinesarcoma3611viraloncogene homoloq;ARAF TCCGGCATTACTATGTCATGGTCATCTGCTACGTCTACTTCACCCGCATCATCGCCATCCGprotein-coupledreceptor108;GPR108 TCCTCAGCCAGCACAGGGAAATCCAGACTCAGGGTTCCAGAAATCCCCCGTTCCCAAACCmyotubularinrelatedprotein3;MTMR3 TCACATATGGATACTTTCACAGTTCAGGATTCCACTGCAATGAGCTGGTGGAGGAATAATDTFT5783;unassigned TCACTGTCACATTCTTTGATGTTTTTGAGCAAAATGCCCCGGCTCCCTTCCTGGGCATCGKIAA1539; 6;ACSL6 TCCTGGCATTCTCTCAGAAGCTGTACTACGACAAGGAACAGACAGTGAGCATGAAGGACAcarbonicanhydraseIV;CA4 TCTAATACCATCCTGCCCATTGTCCTTACCGTCCTGCCCATACAGACTGTGGCTCCTTCCpairedboxgene4;PAX4 TABLE5-continued Sequencesidentified TCCTCCCCGCCGCCCACCTCAGAATTCCTTCCTCCCCGGCCCCTAGTGGGAGCTTAGGCCunassigned TCGCACCAGGGTGGAAAAAAAGGGAATAGTGTTCAAATCACTGATGGAACTGGATGACGCunassigned TCGCACGCGCGCCCTCCCTGGCCGGGCCCACTCGCCACGCGCCCAGCCATGAACCTGGCGunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 O 0 193540 193857 194644 194925 194980 195090 195189 195508 195786 196233 196303 196427 196494 196650 196711 196942 197238197238 197310 197392 197394 197890 No./ABI SEQIDProbe No.ID Probe 414 415 416 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 US 2012 /0295815 A1 Nov . 22 , 2012 40

1,classIG;HLA- protein(NM23B)expressed regulatorofchromatin,subfamilycmember TCTCGGAGTGGCTTTCGCTGGAGAGGTGCTTTGCTGTCTCTCAGACTCAGTCACTGTGTTblockedearlyintransportihomolog(S.cerevisiae)- TCTGAAACACTGGGAGCCTGAGATTCCAGCCCCTATGTCAGAGCTCACAGAGACTTTGGTmajorhistocompatibilitycomplex,classIIDQalpha TCTCAAGTGGCAGTTTCATTATTTAGAATGCAAGGTGGACATCTTTTGGATATCTTTTTCSWI/SNFrelated,matrixassociatedactindependent TGAAAACAGATCGACCTTTACCGGAGAATCCCTATCACTCAAGACCAAGACCGGATCCCANADHdehydrogenase(ubiquinone)1alpha subcomplex,819kDa;NDUFA8 TGAATTTGATGAAGTGATGTTTCCAAAGAACGTGAGGTGCTCTACTTGTGATTTAAGGAAzincfinger,DHHC-typecontaining4;ZDHHC4 Genename/symbol TCTCATCCTACTTAGCCTACCTAGATTTCTCATGACGAGTTAATGCATGTCCGTGGTTGGbrainabundant,membraneattachedsignalprotein TCTGAGTTAACGTTTCAGCTGTATCATTAGACTTGTATTTAGAGCGTGTCACTTCCTCTGYTHdomainfamily,member1;YTHDF1 like;BETIL 2;HLA-DQA2 BASP1;1 TCTCTGTTTCTTGGAAAGGTATCTATTACATCCTGCTAGCTGACTGACAAAACTAAGCAGringfingerprotein11;RNF11 in;NME2 1;SMARCC1 TCTCCGTCTCTGTCTCAAATTTGTGGTCCACTGAGCTATAACTTACTTCTGTATTAAAATHLA-Ghistocompatibilitya TGAAGGACCGCCCATTCTTCCCTGGGCTGGTGAAGTACATGAACTCAGGGCCGGTCGTGGnon-metastaticcell TGACCACCAGGCTATGACGTTCCTGCTGCGCATTACAGAAAGCTTTTAACTGTGATCAGGKIAA1706protein;unassigned TGACCACTATGCTGTCATCAAGTTTCCATTGACCACTGAGTCTGCCATGAAGAAGATAGA60SRIBOSOMALPROTEINL23A TABLE5-continued Sequencesidentified TCTGGAAAGCAGTCTGCCCCTGGAAGTGGTAGCAAGATTCCACAGAAAAGAAGTAAAACTNUCLEOPHOSMIN1 TCTTGCATTAGCAGTGCCCACTGATGGCATTACTCTGCACTATAGCCATTTGCCCCAACTUBIQUITIN TGAATGTTGAAAACTGCAATGTCCGTTATGAGGGCCAAAAATCTGTTTTGAAGGCAGCTAunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 0 O 0 0 0 0 198202 198318 198473 198548 198718 198784 198911 199145 199887 200193 200749 200967 200998 201203 201206 No./ABI SEOIDProbe No.ID Probe 435 436 437 439 440 441 442 443 444 445 446 447 449 US 2012 /0295815 A1 Nov . 22 , 2012

TGACCTCTCCCGCCGCATCTGCCTCTTCCTGACCACAGCCAACCCTGATCTCCTGCTGGAessentialmeioticendonuclease1homolog2(s.pombe); TGAGAACAAGCAGGATGCTGTGGACTACCTCACCTGGACCTTTCTGTACCGCCGCATGACactivatingsignalcointegrator1complexsubunit3-like TGAGCTGTGACTCAACTGCTTCATTAAACATTCTGCATTGGGTATAATSTAAGAATTGTTubiquitin-conjugatingenzymeE2,Ji(UBC6homolog TGCCCTTCCTACTCCTCATAGCATGATATTGTTCTCCAAGGATGGGAATCAGGCATGTGTsignaltransducerandactivatoroftranscription2, TGAGTTCTTTTGAAGCTGATCTCAGGCATCGGATTATTTCTTCTGTAAATATTTCAGAATmitochondrialribosomalproteinL34;MRPL34 TGATACTGAACCTTGATTAATAACAGAAATTCAGGATGTAAAGCCACAGAATGGGATTTAphosphatidylcholinetransferprotein;PCTP TGATGTGACTTACAATTGGATTCAAGATAAATGTGTTCCTCTTGTCCGAGAAATAACATTthioredoxindomaincontaining4(endoplasmic reticulum);TXNDC4 TGCAGCTTGCAATCCGTGGTGATGAAGAGTTGGATTCTCTTATCAAGGCTACCATAGCTGH2Ahistonefamily,memberV;H2AFV TGCCATTGGTTGTATTTTTGTTCTGAGTTTTCGGTGCCGTGTTCCTAACTACTCCATCCCtweetyhomolog3(Drosophila);TTYH3 Genename/symbol UBE2J1);yeast 113kDa;STAT2 TGCGGAGCCTGTTAAAGGTCACTCAGATGTGCAGGTGTTAATCTTCTCTAAAAGCCTGGTSECISbindingprotein2;SECISBP2 EME2 1;ASCC3L1 TGAGAGCCATCCCAGTAACCCGACCACCGCTGGTCTTCACTGGACACCATGAACCACACTINTERFERONINDUCIBLETRANSMEMBRANE PROTEIN TGCAACCTATGGGCTATGCAACTTCTTATGGACAGCCTCCCACTGGTTATGCTACTCCAARNABINDINGPROTEIN TGCAATGCGTGTTGTACATACAGAGGTAACTATCAATATTTAAGTTTGTTGCTGTCAAGAadrenomedullin;ADM TGCATCCCCAGAGTACAGCGAGTTTCCCGCCTCCCGTTAGAGATCCAACACATATTTTTThypotheticalLOC340094;unassigned TGCCCCAGTTTGAGAAGTGGTTGCAGGACAATTTAACCATCGTTGCTGGTATTTTCATAGtetraspanin5;TSPAN5 TGCGCATGTTGTGCCACCACTGCAGCTCCAAGGCCTACCACCTTCAGAAGTCAACCTGTG60SRIBOSOMALPROTEINL37 TGCTACACAAAAGCCAAAAGGTTTCATGTAGATTTTAGTTCACTAAAGGGTGCCCACAAAhexokinase2;HK2 TABLE5-continued Sequencesidentified TGAGCCGAGCCCCTGCCACCAGCCTCCTCCGCACGCCCGTGGAATCAGCACTTTCTGCTTunassigned TGCAGAATTTTATTTTACTTTTTTTAAAGCTATGTTGTTAGCACACAGAACACTTCATTGunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 O 0 0 0 O 0 O 0 0 0 201287 201530 201628 201746 201805 202075 202139 202480 202690 202780 202943 203036 203177 203507 203573 203663 203967 204015 204151 No./ABI SEOIDProbe No.ID Probe 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 US 2012 /0295815 A1 Nov . 22 , 2012

TGCTCCGAGAGAATGGTGACTCCTTGCAGAAAGCCATGATGCAGATACTACAGGAAAAAAmyxovirus(influenzavirus)resistance2mouse;MX2 TGTAGCAAACTCATACTGGATCATTTCAGTTACCTTGAACTAATAGCACATAATGGTTTTV-mybmyeloblastosisviraloncogenehomolog(avian) TGCTTTAAATCACTATCAAAGTTACAAGAAATGTTTGGCTTATTGTGTGATGCAACAGATproteinphosphatase1A(formerly2c),magnesium dependent,alphaisoform;PPM1A TGGCCGCTGTACACTTTTTGCAACTGGTTTGATGTCACATTTCAGCTCCAACTTTGCATCchromosome1openreadingframe108;clorf108 TGTAATACTCCCTTTGGGCGAAGCTAACATCGGTGCCTCCCCGACCTTGCTGACTAGGCAplasmamembraneproteolipid(plasmolipin);PLLP TGTACACTTGTATAAGTACCGTTTACTTCATGGCATGAATAAATGGATCTGTGAGATGCAchromosome14openreadingframe2;C14orf2 TGGACAGCCACCTTTGACCCAGTGCCTACAGATGCCCCGACCAGCCCCCGAGTCTCCGGGSAPSdomainfamily,member1;SAPS1 xia-induciblefactor1,alphasubunitTGGATGTGAAGATATGGTACCTTCTCAAGTGTAGCTCTTTCAAATATAGTCAATGCTGGGhyp inhibitor;HIF1AN TGGCCAAAGTGAGCGAGTTAGGTGATCTTGGTTTCAATTTCCGAGCCTTTGTTAATATGGceroid-lipofuscinosis,neuronal5;CLN5 Genename/symbol TGGCGGCGCAACTCCGAAGAAGAGCGCTAAGAAAACACCGAAGAAAGCGAAGAAGCCGGChistonecluster1,H1c;HIST1H1C like1;MYBL1 TGCTGGTTCTTTGGATAATGGAGTTCTTGTGTTAACAAATTACGTGCTATATGATTTTTTzincfingerprotein518;ZNF518 TGGACCCTGAGCAGCTTCTTGGGCCCTGGTACGTGCTTGCGGTGGCCTCCCGGGAAAAGGlipocalin6;LCN6 TGGTGCTAATGATGGACAGTTAAAAAGATAGCTAGTGTATATTGTTATGGGTCAGTACTTcyclinT2;CCNT2 TGTACCTCTGGATTGGCGGAAGTAAATCTGGAAGGATTCTCACTCGTATTTCCCACCCCThypoxiaup-regulated1;HYOU1 TGTCTCACGTGGTGGATCCGGTGGAAATCCAAGCTCTGGGCTGGTAATTTTTATGAGCATligatin;LGTN TGTCTTGTTTCAGTCCATGATCCCACTGACCTACTCTTGCCTGCTGGAGGGTAATGAGAAaminomethyltransferase;AMT TABLE5-continued Sequencesidentified TGGAGAGAGCAAGTGGCATTTGCTGAAGTGCATTTCCGGTAGAAAACTCCAGTGGTCCCTunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 o 0 0 O O 0 0 0 0 0 0 204296 204604 204784 205183 205249 205389 205731 205999 206122 206232 207292 207649 207683 207727 207803 208381 208509 No./ABI SEQIDProbe No.ID Probe 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 US 2012 /0295815 A1 Nov . 22 , 2012

TBC1domainfamily,member15;TBC1D15 TTAAATTTCGTTTGTCTGGAATATTTTGTATGAGTTCTTGAATAAAACTTGGGAACCAAAsimilarto60SribosomalproteinL22(Heparin-binding TTAGGAGGAAGTTGTGTCCAGTTCAGGGTGCCCTCGGGAGCCCTGTCCCTGTTGCTGTGGSRY(sexdeterminingregionY)-box12;sox12 TTCTGCTTCCTTGGATGTCATTGCTTAAATATAGTCTTGAAGGGCTTGTTTTGAAATATTphosphoinositide-3kinase,class;PIK3C3 TGTTTACATCTCCCACATTCATACCAATATACGTCAGGTTTGCTTAACCATTGATTTTTTproteintyrosinephosphatasetypeIVA,member proteinHBp15);unassigned TTATAGAAAGGACACAAGTTTGTTTCCTGGCTTTACCTTGGGAAAATGCTAGCAACATTAcalpain2,(m/II)largesubunit;CAPN2 TTATTTTAGTAAAATGCCCAGGAGTCCTGGAAGCTACGCGGACTTGCAGAGGTTTTATTTEF-handdomainfamily,memberD2;EFHD2 TTCAAGGTCTGTTTTTCTAACTGAAAAGCTAAGGGCTTGATTCCTAGCCCCGTTCTGTGGunc-84homologB(C.elegans);UNC84B TTCCAAGTCAAGTACTCTGGGACCAGTGCACTGAAGACGATAGGAAGTTCAGCATCAGTKIN,antigenicdeterminantofrecAproteinhomolog TTGAGCCCAGGCATCGTTGAGCATTAACACTCTGTGACAGAGCTGCAGACCCCTGCCTTGcytokineinducedapoptosisinhibitor1;CIAPIN1 Genename/symbol TGTTTCTCGTTTTCATCATATAGACAAAACAGCCCTGCTGCAAAGATGGTCAACGTACCTribosomalproteinL36a-like;RPL36AL TTCCCAGGTTTAATGAAAGAACCCAACTTAGTTTTTCAGTGAATTTGACACCTATTTTTThuntingtininteractingprotein2;HIP2 TTCCTCGTCAGTGGTCAAGGTGTGTCATCCATACAGCTCCATGCCTTTGTCTTTTTTAAAmannosyltransferaseprotein-O1;POMT1 TTCGTTGGGCACAACAGGAACGTATATGACTGCTGCTGCTCCTATGCAAGGGACCTACATRNAbindingmotif,singlestrandedinteractingRBMS3 protein; TTCTCGACATCGAGGACCCATAAGCAGGCCTCCAACGCCCCTGTGGCCAACTGCAAAAAATIMPmetallopeptidaseinhibitor2;TIMP2 (mouse);KIN PTP4A1;1 TTACTCTAGCGCCACTGAATTTTTTCTCTTAGGCTTCCCTGGCTCCCAAGAAGTATGCCGOLFACTORYRECEPTORMOR120 TTCTTCAGTCATGGCATTCGCAGTGCCCAGTGATGGCATTACTCTGCACTATAGCCATTTubiquitinB;UBB TTGAGCTCAACTACATGGTCTACATGTTCCAGTATGATTCCACCTATGACAAATTCCATGGLYCERALDEHYDE3-PHOSPHATE DEHYDROGENASE TABLE5-continued Sequencesidentified TTCCCTCGGTACCATCCGTTCTATCCCATTCCCTGGACCAAATGTTTGCAATATATAACAunassigned TTGAGGGTAGGTCAGGAGTGTCAACGTGCTTGTACATAGAGTGTCTGCTGTAGCTGTGTGATF4

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 0 0 0 0 O 0 0 0 0 O 0 0 TTAAATGTGGAGGCTTTCTATAGCATTCTAAGCTGAGAAGTAGATTGTTACCCAGTAATG O 209686 209738 209946 209952 210426 210617 210742 211052 211174 211734 211931 212006 212174 212468 212680 212834 212992 213386 213392 213429 No./ABI SEOIDProbe No.ID Probe 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 US 2012 /0295815 A1 Nov . 22 , 2012 44

TTGCCTGAGGCAGAGCAAGACGGGTTCTCACCCCTGACTTCTGGAGGCTTCCCTTGAAGCnuclearprelaminArecognitionfactor-like;NARFL TTGTGCGTCATAGAACCCAGAAGGAAATTGAGCAGGAAGCTGCAGTTGAATTATCACAGTubiquinol-cytochromecreductase,Rieskeironsulfur TTTAATCAAGATTAAGAATGAAGTTGACTCTACTTTGACCTTCCGAAGATCATGCAGAGAsuccinatedehydrogenasecomplex,subunitBiron AGGCTTTAATGAGCGTGTGACCTGGGCCACGTCCTGTGGCGTTTGTTCTCCTAGGCCAACcalciumandintegrinbinding1(calmyrin);CIB1 (acute-phaseresponsefactor);STAT3 CAAAAAAGTGCACTGCTCTTCTGTCTATTGTACCGACTTAACCTCTTCCACCCAAGTCCGarmadillorepeatcontaining,X-linked6;ARMCX6 UQCRFS1polypeptide;1 BIOSYNTHESIS,CLASSF TTTCACTTAACCCCAGGCCATTATCATATCCAGATGGTCTTCAGAGTTGTCTTTATATGTaminolevulinate,delta-synthase1;ALAS1 TTTCTCAAAGACAGCAAAAACCTCTCAAACTGAGGAGCAACATTTATTCTTACTAAGCAGsterilealphamotifdomaincontaining9;SAMD9 TTTGGCGTCAGCTTCGAGTGCTTCGCCTCACCCCTCAACTGCTACTTCCGCCAGTACTGTchromosome20openreadingframe67;C20orf67 AATAAAGACCTATGTACTTAATCCTTTAACTCTGCGGATAGCATTTGGTAGGTAGTGATTgrowthfactorreceptor-boundprotein2;GRB2 AGGGAATCCCGTGGGTTGCTTACCTACCTATAAGGTGGTTTATAAGCTGCTGTCCTGGCCsignaltransducerandactivatoroftranscription3 Genename/symbol TTGCTGAGAACCAACTTTCAATAGTCATGAGAGAATCAAATAATAGATGTCCGTACAAGTWilmstumoriassociatedprotein;WTAP sulfur(Ip);SDHB ACCCGGAAACAAACTTGCCAGTTGGGTATCCTCCTCAGTATCCACCGACAGCATTCCAAGphospholipidscramblase1;PLSCR1 TTGATATTGTAGACGTCAAGGGAATGGGTACTGTTCAAAAAGGAATGCCCCACAAGTGTTribosomalproteinL21;RPL21 TTGCTGAACGTTCTGATTCCACCCAATATGCCATGTACGCGAACAGGGAAGAATAACGTTnucleoporin50kDa;NUP50 TTGTATTCATTGTGGATGTTAAAGCCAACAAGCACCAGATCAAACAGGCTGTGAAGAAGC60SRIBOSOMALPROTEINL23A TTTACAGCACTGTTTTTTATGTAGTTACAACATGATGTGATTGTAGCTTTTTAAACTATGPHOSPHATIDYLINOSITOL-GLYCAN AAACCATTGAGAAGATGCAGGAATAAAGTAATCTTATATACAAGCTTTGATTAAAACTTGribosomalproteinL26;RPL26 AAGGCATCATGGATTCCCTGTTCCAGTCCTTCAATGCCTCCATCTCAGTGGCCAGCTTCCMAX-likeproteinX;MLX ATAAATTTGCCCAAAATCCTAAAGACCGGGAAAAGGGAACCATTGAGCTTGGCAAAAAAACD8bmolecule;CD8B TABLE5-continued Sequencesidentified TTGCAAGACATACCAGAGAAGGACTTCATTGTTTTCTGCTCTTCAACCTCATATAACGTGCASPASE-1

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 0 0 0 0 O 0 O 0 0 0 0 213480 213580 213805 213922 214614 214774 215062 215112 215448 215752 216334 217279 217674 217758 218201 219140 219147 219372 219934 No./ABI SEOIDProbe No.ID Probe 506 507 508 509213915 510 511 512 513 514 515 516 517 518 519 521 522 523 524 525 US 2012 /0295815 A1 Nov . 22 , 2012

GAAGAGATAGAGATAGTAAAATGTGAAAATGCTACAGTTATGGATAAGGCCCGAGCTTTGinhibitorycaspaserecruitmentdomain(CARD) GCCCCACCAGTACCCATATGCAGGACTTTATGGACAGCAGCCTGCTAACCAAGTCATCATpleckstrinhomologydomaincontaining,familyB GCGCAAGAAGTTCAACATGGACCCCGCCAAGGGTATCCAGTATTTCATTGAGCACAAGCTpleckstrinhomology,Sec7andcoiled-coildomains GCTATATATACTCGAGCACTCTCCATATAATGCCTCCATTTACCAACTTGCTCTTAAAAAchromosome9openreadingframe66;C9orf GCCCACCTCCGGGACTGACTGGTCAGAAGCCACCCTTGTCTACGTGGGATAATTCTCCCCtrinucleotiderepeatcontaining6A;TNRC6A (evectins)member2;PLEKHB2 GGTCAGAACCGTGATTCGAGCCTTTGTGAAATGCACCAAAGCCCGATACCTGAAGAAAAAmitochondrialribosomalproteinL20;MRPL20 TTTCCTGACGTTTTACATTTCCACTTTCCTATTCCATTCATTAAGCTAGCCAACAATCCAmakorin,ringfingerprotein1;MKRNI Genename/symbol CTGATAAAGGAAGCAGGAAGCGCTATGAACCATCAGACAAGGACAGGCAGAGCCCTCCTCconservednuclearproteinNHN1;unassigned GATACCCAAAGGTCAAGAACACAGTGATTTTATTAGAAGTTTCATCCGCAAATTTTCTTC2'-5'oligoadenylatesynthetase, TACAGAACTAGACCAGAAGACATTTGTGGATAAATCTGAACTCACTTCCTGTGTGTAACTcoiled-coildomaincontaining23;CCDC23 unassignedprotein; 69/71kDa;OAS2 PSCD4;4 GCTGCCAGCTACCAGCCTGGCTGGCCCTGTCCTGTCCACCCTCATTGCCCCAACTCCCATWDrepeatdomain33;WDR33 GGAGGGCCTCCTGCTCCTCCTGGCGCTAGGAGAGCCCCACTCGGTGTGGCACGGAGACACribosomalproteinL7a;RPL7A GGCAGGTTAGAGCTAGTGTATGTTACTGTGAATTGTAATGTAGTTGGATTGTACAAATTAFASTkinasedomains5;FASTKD5 GGCGCGGACCAAAGCGATCTCTTCTGAGGATCCGGCAAGATGGCAGAAGTAGAGCAGAAGribosomalproteinS15;RPS15 CAGCCCCCTCATCATGCAGTTGCTGAGAGACAACCTAATAACACTGTGGACATCACACAG14/032003 TGGAATGTGAAGCGTATGCAATTCCTTCTGCCTCCCTCAGCTGGTACAAGGATGGACAGGhemicentin1;HMCN1 TABLE5-continued Sequencesidentified GATGCTGGAGGGAACAGTGAAGTGCAGCAGATGATGCTTCGAGGGTGGCTTTGAGGCCACDKFZp58611420 GTCTTTATGAAGAACTCCTTCAAGGATGTGGACCATCTGTTTCAAAAGAAATTAGCGGCCunassigned GTTCCTGGCTCGCCGTCTCCGCTGCCGCTTGACCGCACTTCTGGAGGGCTCCGCACCTTGunassigned TGAACTTTCTGCTGAGCGAGCACCGCCAGGCCCTGGCCTCCGCCAAGCACCGAGGCCCCGunassigned TGCAGAGTGGCGTCCTCAAGTCCCTCTCCCTGCACCCCTGCCCCTCACGCATAGTGCCACunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 O O 0 0 0 0 0 0 0 O 0 0 0 0 0 220398 222165 222692 223130 223180 223539 223554 223717 223796 223896 224201 224302 224390 224678 224990 225234 225433 226380 226634 226833 227814 No./ABI SEQIDProbe No.ID Probe 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 US 2012 /0295815 A1 Nov . 22 , 2012 46

AGGGCAATTTACTTTTTTGTACTTCAGACTATCTTGATTGTCAAAGTGTACGAACTGTAAGUANINENUCLEOTIDE-BINDINGPROTEING, Genename/symbol ACAAAATTCCTAGCACATGAGAAGATCTGGCTCGACAAATTCAAATATGAAGATACAGAAELONGATIONFACTOR-1BETA,DELTA CCAAAGTGGACGAGGTGAAGTTTATGATAAAGTTCCAAATGAAGAAGGTGTTACCTCTGGsimilartoribosomalproteinL10a;unassigned ALPHASUBUNIT ATCAGCATTGACAAGGGACACAATTTCTGTCTGATCTATGACACCAAGGGTTGCTTTGGT30S/40SRIBOSOMALPROTEINS4 CCCCCAGCTGCTGTTCTCGTCTTTGGAGGACCCGGCTTTACTGGTGCCACATGCCTGCTGhypotheticalproteinLOC254099 GCCTTGGCAGAGGCGTCTCCCCACATTCTGACTCCTGGTCCCCTTGAAACCCTGTTGGTGhypotheticalproteinFLJ25404;unassigned GTGAAATGCATGTTTAGCAAGTGTTAGGTACTGTATTTGAACCAATAAATGTGAATCCTThypotheticalproteinLOC253842 TABLE5-continued GCCGAAGGACCCTGTGCTGCCTGTGACTTTGGTATGTGTCCTCTGGGAACAGAAGCAGGGLATECORNIFIEDENVELOPE Sequencesidentified AAAAATAAAGCTGTATGACTTAGTGCTGAAGGATATGAATTAGGCATAGCTCTTGGGTTGunassigned AAACGCTCCCTGTATCTTGCTGTACTGTTAAAGAAAGCTGAATTCCACATTGCCAACAAACHST11 AATCGAAAAGAAGCAAATTGCCATGACAGATAACACTTTGATTGCTCAATCTCTTGGTAAunassigned AGAAGCCCCTTACTCCCAAGTCTGAGAGTTCCAAGTGTGGTAAAAATGGCAACCTTTGCTunassigned AGATTCTGCAAAGGTGCCAACCCCTTGCAAAGGAGCCCTGGCATCAGAACCCTCCCCAGGunassigned AGGCCCCACCTTCCAGTGAGAACTCATGCAGAGACCCTCAAACCAGGAAAGCTGGGTTGTunassigned ATTCATGACGTGTGAAATTTCAGTTTCTCTGGAGTTTGTCAGACGGCGTGGGAACCACGCunassigned CACTGCAGGTGTATATAGATGCTTTCTGTCATACTGTGTTTTCAGATGCAGAATTTTAAAunassigned CAGGCGCTGACCCACGAATGCAACTCTCAGCCGAGCTGTCCCTGCCGGATTTCAAACAGCunassigned CTGACTGGAAACCTTAGCCCCCAAATATGAAATGCCTTCTCTAGATTAAAAGGGTGCAGAunassigned GGTATCTCCATTGCACTCTATTTGCCACCTCACCCTGAAGGAAGGTACGAGGGCCCCTTCunassigned GTTCCAGCTTTACCCCAGCCTTAATCTTTTAAAATGTATATTTTCCTTAGCGTTGATTTTLOC285835 TACGTGTTGGAAGAAACAGACACCTTCCCATCCCCAGCGTTTGTTCAGTGCCTTGGTTGGLOC144486 TCCCACTGCGGTCACTTCCTAGGACTCAGACGGTCCTGCTCCCACTGCGGTCACTTCCTAunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 O 0 O O O 0 0 0 0 0 0 0 227967 228018 228350 228418 228829 228955 229149 229178 229386 229610 229869 229998 230179 230388 230983 231881 231927 232462 232665 232784 232947 233271 No./ABI SEOIDProbe No.ID Probe 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 US 2012 /0295815 A1 Nov . 22 , 2012

AAACGCTGGGAATCTGAGCGCATCCTCTCCTTCATCCCTCCTGATGGAAACTTCCGCCTGadaptor-relatedproteincomplex3,mu2 AGCCCTTCCTCTGTGCTCCGCCTTGAGAGCAGTGTTTCGGACGCTGGGAAGCGTGCTGTGfamilywithsequencesimilarity90,memberA11 AAATACACAGAGGTCCTCAAGACCCACGGACTCCTGGTCTGAGCCCAATAAAGACTGTTAsimilartoribosomalproteinL13a;unassigned FAM90A11Ppseudogene; Genename/symbol TTGTGAAGTCCAAGGAGGTCAAGACCAAGATCCCAAAGGGCATTAGGTGCAAACTCAATChypotheticalgenesupportedby BC013438;unassigned subunit;AP3M2 AGATGGCGCTGAAAGCAAATAAGGAAGCTCCTGCCCCTCCTAAAGCCGAAGCCAAAGTGA60SRIBOSOMALPROTEINL23A unassigned CCATGCTCTCTCTCCATAGGTCCTGTTTTACTATGATGTAAAAATTAGGTCATGTACATTSMALLNUCLEARRIBONUCLEOPROTEING CGTGGACCGCGCTGCGAGCCTCGGAGACGCCGTAGAAGGAGACCTGCTTCCGGGACTGGAthyroidadenomaassociated;THADA GGAGGCGCAATAAGACACCCCTCCACAGAGCTTGGCATCATGGGAAGCTGGTTCTACCTCFLJ43339protein;unassigned TGACTGTCACAGGCAGGCTCAACAAGTGTGGAGTGATCAGCCCCAGATTTGATGTGCAAC30SRIBOSOMALPROTEINS8 TABLE5-continued Sequencesidentified TTTCGATGGCTCTAGTACTTTTACAGTCTGAACAGTGACATGTATCTCGTGCCTGCTGCCGLUTAMINESYNTHETASE AGAAAGAGAATCATTGTCTCGCCTTCTGTGTTCCACTCTCCTCCTCACTGGTGCCTTTTGLOC219690 AGTCAGCCCTGTGGCCCCTCCACGGCCCCCAGGCCCAAGGCCATACGGGCACTGATGGCCunassigned ccccATCTTGCATGTTGTGACACCTICACCAATAACATAATCATGTATTTcccTGCTGTCORTE156P CTAATACCTGCCAACCTACTCTTAATCAGTGGTGGAAGAATGGTCTCAGAACTGCTTGTTunassigned GGAGGCATGTCCTCAGGCCTGGGAGACCAGGCTGGCCCCAGCCTCCCTGTGCGGTCAGGGunassigned GGATCCCGGTCCAGTCTCCTGACTGCGTAGAGATCCCTCTTCTTCCCGAAAGGCAGTGGAunassigned CACTGCAGGTGTATATAGATGCTTTCTGTCATACTGTGTTTTCAGATGCAGAATTTTAAALOC283824 GTTTTTAGGATCAGTACTTTTTAATGGAAAAAACTTGACCAAAAATTTGTCACAGAATTTunassigned TCAGGCATGTTACTGGTAGTTCCTTTTGAGTCTGACATTCTAATAAAATAATTTGTAGAAU520 TGAAGCAGTGTGCAGATGTTGAAGGAGTATAATGCAAGATATTTTTTTCTTTTTTATAGTunassigned

occur.)oligonucleotideSequences

(Freq. of 0 0 0 0 0 0 0 O o O 0 0 0 0 0 O O O 0 CACGCTGTATGTTCCCCTGCGAGCACCCTCCTCTTGGCCTCTGGCCAAGTCCCACCCATC 0 234280 234317 234406 234426 234587 234622 234633 234677 234862 234963 234980 235086 235093 235377 235378 235380 235381 235600 235698 235774 235783 No./ABI SEOIDProbe No.ID Probe 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 US 2012 /0295815 A1 Nov . 22 , 2012 48

CTCTCCCTAGGAGGCCTGCCCCCGCTAACCGGCTTTTTGCCCAAATGGGCCATTATCGAAgeneraltranscriptionfactorIIB;GTF2B GAATGAGAACCCTACTTGCCTAAATGAGGAATGTCTTTCCTACCATCTAAAATACGAAGGheterogeneousnuclearribonucleoproteinA3;HNRPA3 Genename/symbol TGGAAGTCATCATTGCAGATGCTTAAGTCAACTATTTTAATAAATTGATTACCAGTTGTT40SRIBOSOMALPROTEINS20 TGTTGGCCTTTTAAGCCCAATGGTCTATCAGGAAGTAGAAGAGCAGAAACTACATCAAGCIQmotifcontainingB1;IQCB1 CAACTCTCCTCTGAAGCCCTGGTGGCTGCCCAAATTTGTGCCAATAAGTACATAGTAAAA60SRIBOSOMALPROTEINL10 CAATCATGTTGCCGTATCAAGCAGAAAATGTCACCACTATCTGGAGAGTTGGACATGTTTRIBOSOMALPROTEINL39E GGGACCGTGTCGGCCCAGATCGAGGGTGGCGTTCATGGCCTGCACTCTTACGAGAGGTGGINOSINE-5MONOPHOSPHATEDEHYDROGENASE TCCAGATACCTAATAAGATGCTGGAATGTAATCCCTGGACAATCCGTGTCCTGGCAGCATbreakpointclusterregion;BCR AGGAGGGATGTTACTAGAAATGCACAAAGTGGGCTGAACACAGTGGCTCACACCTGTAATZINCFINGERPROTEIN393 CAACATAGTGAGACCCTGCTTCTAAAGCATTTTCTTGGTGTTACTCCTGTAGATCCTCACFATTY-ACIDAMIDEHYDROLASE CGCCAGTCCCTCCGACGCCGACCTCAGAGTTCCAGCTGCTGTGGCAGTGGCAGTGGCCAGlatecornifiedenvelope5A;LCESA TABLE5-continued Sequencesidentified TTGCTTGTGGATGACTGACCAGGAGGCTATTCAAGATCTCTGGCACTGGAGGAAGTCTCTNUCLEOPHOSMIN1 TGCCGTGTTCCGGAGCCAGCAGCAGGAGACTGTGGGCCTTGAGGATGTGGTAGTGCATGGunassigned CCAGATTAACAGTCTTATCAGAAGAACGAACTAAGGTGTCTACCATGATTATTTTTCTAAunassigned GTGGTCAACCACCTCAGTAAAATTGGAGAGGATTATTTTGCATTGACTAAACTTACAGAAunassigned TAGCCCTGTTCTCTCCTGGTACCTCCAGCATCCCAATCAATTCCTCCAGATCCGCCTGAGunassignedTAGCCCTGTTCTCTCCTGGTACCTCCAGCATCCCAATLAA. TTAGATCCTCCTCTTCAAATGCTGTAATTAACATCACTTAAAAAAACTTGAAAAAATATTunassigned GGGCCCTGGATCACCAGCCTCCCTCCACCCAGAATGCCCCGTCCACTCCACTGCCCACCAunassigned ACTGTGGTGATTTTTCATATTCCAGTACTCCAGCCTGGGTGACAGTGCGAGACTCTGTTTunassigned CCGCAGGTCGTCCATCCGCAACGCGCACAGCATCCATCAGCGGTCGCGGAAGCGCCTCAGNCF1 CCTCCTTCATTGCCATCTGTGAGTTTCCTGCCTGAAGAGGCACGTTCCTCAGCCCCCTCCMBL1P1 CGAGCTGCCTGCGCTGGGCAAATGACCTCCCCGCGAACGGGAACGCCCGGACGAGACAACunassigned occur.)oligonucleotideSequences

(Freq. of 0 0 O o 0 O O 0 o 0 0 o o O 0 O O 235812 235833 235877 235960 236300 236307 236371 236685 236756 236794 236829 236955 237093 295023 318897 361497 412092 416900 424910 426464 443501 474728 No./ABI SEOIDProbe No.ID Probe 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 US 2012 /0295815 A1 Nov . 22 , 2012

GCTGAGCTCAGCCCCTGTGGCCTCAGAGCTGCAGGCCCCTCCCGGGTGTCAGAGCACTGAsmallopticlobeshomolog(Drosophila);SOLH GGCTGAAGTTGCAGTGAGCCGAGATCGCGCCATTGTACTCCAGCCTGGGCGATGAGCAAAchromosome3openreadingframe34;C3orf34 TCTACAGCGTGGTTTGCCTGCCTGTCTGCCCTCCTGGATGCTATTAAAGCTTTGTTTTGTADP-RIBOSYLATIONFACTORLIKE4,ARL4 Genename/symbol TTCTCTCCACAGTATGGCTTCACCTGTTCCTGAGCGCCCTGCTACCCTCTTGCTAACCTGkelchdomaincontaining4;KLHDC4 CCAGGAGCTCCGCCCCCTCTGGGTTCCCAGGACTCTGATTGGTCGGCGAGCCAGCCCTTCFBJmurineosteosarcomaviraloncogenehomolog GGATCGCTGCCACCTTTTACCTAGGCCTCCCCACCATGGCCTCTGCCAGAGCCAGCTCCTASPARTATEAMINOTRANSFERASE GGCCTAAAAATAAGGCCCATGTCCACTGTCCCCTGCATTAGTGTTGCTGTTGGAACAATA60SRIBOSOMALPROTEINL21 TTTGATGAGCTGAAGGCTTCAGAAGGTTGGTAATAACAAACTTCTCTGAGCTAAAGGAGGL1TRANSPOSABLEELEMENT-RELATED B;FOSB TABLE5-continued Sequencesidentified GGGAACCGCGGTGGCTTCCCTCGCGGAGGCAAGGCCAAAGATAAGGAGTGGATGCCCGTCunassigned GGGCCGAGAGAATTTTGAGCTCTAGCCGTCTTGTTCGCCGGCAATAAAAGGACTCCTGAAunassigned GTGACCAAGCCCCTTCTGCTGCTCCATGCCCCTGCTCGCCGCAGTGTCCCAGTCACCAGGunassigned TAGAACAATCCTGTGAAGAACCTTCTAAATSTGATGGTATTTATGGCTGTAAGTTGCTGGUNCHARACTERIZED ?ccTTTCTAGTTATTTCTATTACTICAccc???????c??CAACTICACCAcc???????unassigned TGGAAGGAACAAATTCCAGACACACCAGCACTTTGGGAGGCTGAGGCGGCTAGATCACTTUNCHARACTERIZED AACTTGGAAAAATGTTTTTGCAAAACTTGATGATCAAGCTGAACGTAGAACGATATTCCTunassigned ACACTCCGGTGAGGTTCTGACTGGCCCTGGGACATCACCTGCTCCAGGATCCTATGTGGCunassigned ACCCCTGCCCACTGCGGCAAACCCCTACTTCTGGTTTCCTTTGGAACCCCTTTGTTATTCunassigned ACTCAGGCCTCCTGCAATGGCTCCATGCTGGACCAGCAACAGCTCCACGCCGGCTGGACTunassigned CAGCGGGCAGCAGACCCCAGAGTAGCAGGGAAGACAAGCACTTCAAAGAGGCAGCGTCAGunassigned CAGGTGCTCGTGTGCACGTGAGCGGCTCTTCCTGCTGACTGACTACAGCTAATTGACAAAunassigned GCAAGCGTGGCATCATTGGCTAGAATGTTTGAAGACCAGTCTTAACATCTGATTATATTTATP5L2 GCCAGAACCATCCAGCTAAGCCCCTCGCAGATTCCCCACCCACGAAAATGCTGAGATGACD2182090E

occur.)oligonucleotideSequences GGCCTAAAAATAAGGCC (Freq. of 0 0 0 0 0 O 0 ? O 0 O 0 0 O O O O O O 0

518907 531903 536912536912 539197 541108 545687 565070 588118 613619 61616050 643139 673310 687856 694146 695191 695718 696102 700852 701053 701997 707035 707472 No./ABI SEQIDProbe No.ID Probe 612 613 614 615 616 617 618 619 620 621 623 624 625 626 627 628 629 630 631 632 633 US 2012 /0295815 A1 Nov . 22 , 2012

5

/

4

(UBenzymeE2D1gating membrane(neutralsphingomyelinaseII);SMPD3 AGCAGCGGCTGCAACTGCGGCTCCTGGCCAGACCCCGGCCTCAGCGCAAGCTCCAGCGCAeukaryotictranslationinitiationfactor3,subunit5 GCTCACTTTGTTTCTCGGTGGCTGACTCGTCTCTGTCGCTCACTCCCTCTGTCACTCGCGchromosome14openreadingframe78;C140rf AAATACGTGGGACAGTGTCTTCTCAGAGACAACCAGCCTTGAAGGCTACAGGTGATGAGAproteinimmuno-reactivewithantiPTHpolyclonal AAGAAACTCACTTTCCCTGTGGCACGTTATGCTTCAGAATTAAAACAATGAAGATTAAAArabphilin3A-like(withoutC2domains);RPH3AL AATTTTGTGCCTACTCTAGGGCAAACAGAATTACAATTGAAGGAGTTCCTATCTATCTGTAHA1,activatorofheatshock90kDaproteinATPase ACTCCTGGATTATAGATTAAAAGTCTCTGTAGACATCTCTGTGAAGAGCAAGCTATCATTsignalrecognitionparticle14kDa(homologousAlu RNAbindingprotein);SRP14 antibodies;unassigned AAATATCCTCCTGTGACACCTTCCCCACCCTGCCAGTCAAAGTATCCACCCAAGAGCAAGsmallproline-richprotein2A;SPRR2A homolog2(yeast);AHSA2 ACGGGTCACCCGAGGCCCATACCAAGACTCTGTTCCTGCCCTAGGCCCAGTCTCAAAGGAsphingomyelinphosphodiesterase3,neutral kDaEIF3S5;47epsilon, AGGATAAGGATGCTTAAAATGGAAATCATTCTCCAACGATATACAAATTGGACTTGTTCAforkheadbox01A(rhabdomyosarcoma);FOXO1A homolog,yeast);UBE2D1 Genename/symbol AGAGGTGGAGACCATCTCCAAGGAACTGGAGCTTTTGGACAGAGAGCTGTGCCAGCTGCTgasdermindomaincontaining1;GSDMDC1 GACGTGTGAGGTCACTTCCTGCGTGTTGGGTGGCTTCCTGCGGCGTTTCCACTCTCGCTCribosomalproteinS13;RPS13 AAATTTCCAGATCAACATGGCTATGGTATTTAGTAATGGCCCAGCTTAGAGACTTCAGCTtropomodulin1;TMOD1 AATCACAGCCACTTGACAAGAAAGGATATTCATTATTTTCAAATGGCTTTTGGACTATCATHUMPdomaincontaining1;THUMPD1 ACATCAAACTGCCTGGATTTTTCTACCACCCTGTTACATCATAACAACTTCTGAAACACAGM2gangliosideactivator;GM2A ACTCTATGCATTGTGGAACACCTTTAAATCCATCCTGATTCAAGTTGCCTTATTCAAAGTMULTIDRUGRESISTANCEPROTEIN2 totubiquitin-conju TABLE5-continued Sequencesidentified TATTTTGAATTGATTGTGGCATCTGCCTGCTTCCCCATTAAAACTGAATAAAATCTTTAAunassigned TCCAGTCTCAGCAAGCTGCCCTTTAAAGAGGGTGATATGGTTTGGCTCTGTGTCCCCACCunassigned TGCAGACCTGACCCACATGTCCAGGAGCCTGTATGCTGGCCCCCTCTACCCTTGAGTGCCunassigned AGTGAATTAACTGTGTCTCCCTTGTCTTAGGATATTCTGTAGATTGATTGCAGATTTCTTubiqui AGTGTGGGAAGATGTCTCCCTGACCTCAATGTCTGTCTGCAATTTATGGAGATGACCACALOC199725

occur.)oligonucleotideSequences

(Freq. of 0 0 0 10 10 10 10 10 10 10 10 10 10 10 10 10 10 7080120 711916 712531 713949 102001 102047 102451 104220 106983 108231 110074 112934 113660 113742 117044 118174 120624 122946 123404 No./ABI SEQIDProbe No.ID 63810480018 Probe 634 635 636 637 639 640 641 642 643 644 645 646 647 648 649 650 651 652 653 US 2012 /0295815 A1 Nov . 22 , 2012 51

ATCAGAACAAGCCCTTCAGTGTGCCGCATACTAAGTCCCTGGAGAGCCGCATCAAGGAGGtranscriptionaladaptor3(NGG1homolog,yeast)- CAGGTGAGGAAAGTTAGGAGATATTCATCTTAAGAGATATCCTATTTGGCAGTCACATGTfamilywithsequencesimilarity49,memberA;FAM49A CCATCCCACATTCGGACCCTGCCCATACCCCTGCCTGGGTTTTCTAACTGTAAATCACTTATP-bindingcassette,subfamilyC(CFTR/MRP) AGTTGTAACTCTGCGTGGACTATGGACAGTCAACAATATGTACTTAAAAGTTGCACTATTcalmodulin2(phosphorylasekinase,delta);CALM2 CCCTTGTGTCTCAGGTGTGGTCCCTGCCTGCTTGATGAAGTTGCTCTGTTCAAGCCTTTGglycosyltransferase25domaincontaining1;GLT25D1 CCTAACCCTGTACTAACCTGCTTGGTGGACTTGGAAAAGACTTGGCTCTGTCGGGAAAGGphosphatidylinositol3,45-trisphosphatedependent CGGGACCATCTGATGTGATGTGAATACTCTTCCCACATACATTAAACACACTTAAGTGAGsolutecarrierfamily19(folatetransporter),member (mitochondrial)putative;PARS2 CCCTGGATTCAAATTAAGTGCAATATTTTGCAAACAGCTCTTCTTAGGGAAATCTCCTGAtransmembraneandcoiled-coildomainfamily RACexchanger1;unassigned CGGGAGAGATTTACTTTGAACATTGTCAGTTGCAGCAAAAATTTACTACACAAGATTATTcoiled-coildomaincontaining90B;CCDC90B CTAGTTGGATGGCACAAGGCTCTTCACAGACGCATCTGTAGCAGAGTGGAACTTGTACTAtranslocaseofoutermitochondrialmembrane7homolog(yeast);TOMMY Genename/symbol member8;ABCC8 like;TADA3L ATCATGGCAGTCCCTGTCATCTCTGAGTGGGCCTTTGCAAGTGGTTCCTGACATTGATGAserine/threoninekinase40;STK40 ATCCAGCACCAGTCAGACCAATATGTCAAAATTAAGCGTAACTGGCGGAAACCCAGAGGCribosomalproteinL32;RPL32 ATTCTTATATTTTTCTTTACTAATTTTGGATTTTTTTTCTTTGAATTATTGGGCAGGGAAHSC70-INTERACTINGPROTEIN CAGTGGTGGCCGTAGACTTGGCTCGGAACTTAGTGGCACCAGAGTAACTCTAGTCAGTTAnucleoporin62kDa;NUP62 3;TMCC3 CCGCCGACTTCACGGCCGAGGCCCACGCCGCCTGGGACAAGTTCCTATCGGTCGTATCCThemoglobin,zeta;HBZ CGCCCTTCCTAAGTTATCGGCCTGCGAGCCGGAGAGACAATGGAGAGAACTGCAGAGGCCzincfingerprotein787;ZNF787 1;SLC19A1 CTACCGTCAAGTCTTTGAACGCCATTACCCAGGCCGGGCTGACTGGCTGAGCCATTACTGasparaginesynthetase;ASNS CTCTCATTCTCCATAGTCTGTTTCCTGGAAAGTCGATGTAATTAACTGATGGCCCAAAAAprolyl-tRNAsynthetase TABLE5-continued Sequencesidentified ATGGGCGCCCAAGGATTCTCCCCGCAGGCTCGCAGACTCACCTGATCACCGGGCAAGCGCunassigned

occur.)OligonucleotideSequences

(Freq. of 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 123750 125313 125540 125665 128233 129584 136737 137199 141516 143933 144117 144454 145045 148686 149707 149721 151108 151523 153385 No./ABI SEOIDProbe No.ID Probe 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 US 2012 /0295815 A1 Nov . 22 , 2012

CTGTCGGAGGCCGGGCTGCGCCTGCTGCACTTCCTGTTCATGTACGACCCTAAGAAAAGGcyclin-dependentkinase(CDC2like)10;CDK10 GGCCGCCATCAATGCACGCAAGATGAAATTTGCTCTGCTAAAAGGCTCCTTCAGTGAGCAproteindisulfideisomerasefamilyA,member6;PDIA6 GTCAGGAGTCCCAAAGGTCAGTGACAGTTTCTCAGAAGAGGCCCAGCGTCCACCTCTCTCproteinphosphatase2A,regulatorysubunitB'(PR GATGATGTAGTTGATTATTTCAAGAGACAAGGTTTCTCCTATCAGGGTCGGGCTTCCAGCNOL1/NOP2Sundomainfamily,member5;NSUN5 GTGTGGGCCATCTCGGCCCTGGTGTCCTTCCTGCCCATCCTCATGCACTGGTGGCGGGCGadrenergic,beta-1receptor;ADRB1 Genename/symbol GCGGGAGAAGCTGACGGACTGGAAGGACTTCTTGCTGGTGAAGAGCAGGAGGAACATCACHermansky-Pudlaksyndrome1;HPS1 cytokinesis9;DOCK9GCTTAAGGAATTATGTGAGCTTAAAACTAGTCAAGCAGTTTAGAACCAAAGGCCTATATTdedicatorof GTATGAGGATGTGGCACTGATCAAAGACCATACACTTGTCAATTCCTTGATTCGTGTGCTRAB6interactingprotein1;RAB6IP1 GTTCTTAGTTGGTGGAGCGATTTGTCTGGTTAATTCCGATAACGAACGAGACTCTGGCATiroquoishomeoboxprotein6;IRX6 GGAAAGATCTGTGAAATGCTATCTCTCCTGAAGCAATACTGTTGACCAGAAAGGACACTCBCL2-relatedproteinAl;BCL2A1 53);PPP2R4 GACAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGACD8bmolecule;CD8B GACCGTGGTGAAGAATTGCATCGTGCCCATCGACAGCACGCCCTACCGACAGTGGTACGA40SRIBOSOMALPROTEINS8 GCGTCTCAGGCAGGCATGACTGGCTACGGGATGCCACGCCAGATCCTCTGATCCCACCCCtransgelin2;TAGLN2 GGATCCTGGTATCCGCTAACAGGTCAAAATGCAGATCTTCGTGAAAACCCTTACCGGCAAubiquitinB;UBB GGCTTCCTTCAGCGTTCTTCCTGTTGTATTCTGAGTATCGCCCAAAAATCAAAGGAGAACSWI/SNF-RELATEDCHROMATINBINDING PROTEIN TACCGAGGCCCCTACAAAGCCTTCAGAGTAGATATCTCTGCCAACGTGAGGACAGAAGGA60SRIBOSOMALPROTEINL29 TABLE5-continued Sequencesidentified GAATTTTTGTGCTCTTTTCCCTGTGTACATGGTGGTTCTATCTCCAATAAAACTTTTGTTunassigned GGACCGCTATAAGGCCAGTCGGACTGCGACATAGCCCATCCCCTCGACCGCTCGCGTCGCunassigned GGCCCCAGGCCGGTACTTCGCCCACAGCATCCTGACCGTGTCCGAAGAGGAATGGAACACIGHM GGCCGTCACACCTACCCTGTGCAGCGGAGCCGGACCAGGCTCTTGTGTCCTCACTCAGGTSYNAPTOGYRIN2 TATGGACTCTGCCTTCATGTCATCAGTTAAAGTGCCCTGCACACCTGCCTGTCCTAGGTCunassigned

occur.)oligonucleotideSequences

(Freq. of 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 156494 161521 161967 162490 166400 172174 172296 174201 174875 175820 177127 178394 178526 178566 179521 183635 184060 187114 187876 190261 192398 No./ABI SEOIDProbe No.ID Probe 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 US 2012 /0295815 A1 Nov . 22 , 2012

TCCAACAAGTACGGCGTGTTTATGCGAGTGAGCGAGGTGAAGCCCACCTATCGCAACTCCpurine-richelementbindingproteinA;PURA TCGTTCTCTGCACTTTCCCCCCTGCCTCCCAACAGTGGCCTTCCTATCTGGCTTGGTGGGacyl-malonylcondensingenzyme1;AMACI TGGATTCAGTGCAGTAAATAAAACACAGGAAGTATTCTGGTGGAAAAATACCTTGTATTTproteintyrosinephosphatase-likeAdomaincontaining TGGCTCAACTCGAATCATCACCAGATTGCGGAATCCAGATAGCAAACTTAGTCAGCTGAAbromodomainPHDfingertranscriptionfactor;BPTF TGGGAAGTAAAGACATAGGATCCAAGAATGAGGGTTCCCCCAGCCGGGCCTGCAGCCCAGmediatorofRNApolymeraseIItranscription,subunit 25homolog(S.cerevisiae);MED25 TGTTTATCCATCAGCCCAGAGCACTTACTGAGAGTAAAGAGGCTCTAGCCACCCCCTTACchromosome7openreadingframe25;c7orf25 TTTCTCATAAGCATTTGCCCTCACCATGGTTTATAAAACTTTGGGAAAACGGAATATTCAUVradiationresistanceassociatedgene;UVRAG Genename/symbol TCCTCATATTCATTCCAGTCTGGATATTTGATACTATCCTTCTTGTCCTGCTGATTGTGAtransmembraneprotein60;TMEM60 TGAAGAGGCCATAGTACCTCCTGTTTGAAGTTGTTTATTCACATCTATCTTATTTGAAGAtestisexpressedsequence10;TEX10 TGCCCATTCCCCATCATCATCCGTTTTACCTTAGTTAGCATTTTTCTTATCATTTTTCTTankyrinrepeatdomain17;ANKRD17 TGTATTATCTGCTTTGCTGATGTAGACAAGAGTTAACTGAGTAGCATGCTTTATTAAGCAtransmembraneprotein50A;TMEM50A TTACTCCTGCCCAGTGACTGTGACCACTGTCCGTGTTGCCTTCTTGAACAGCGATTCCCCsyntaxin1A(brain);STX1A CCAAGCTGCTGTACTTCAAAGGAAACAGATSTAGCACACTGCTGCACCCCTGCTTCCACAGprotein-coupledreceptor107;GPR107 PROTEIN1,2 TCGAGGTGGAGCCGAGTGACACCATTGAGAATGTCAAGGCAAAGATCCAAGACAAGGAAGubiquitinC;UBC TGCAGTATTTATGGCCTCGTCCTCCCCCACCTAGGCCACGTGTGAGCTGCTCCTGTCTCTtubulin,beta3;TUBB3 2;PTPLAD2 TTGTTGTAGGCATCAAAAGAATTGATGGCGTGAGTTTACTGGTGCGGAAAACCATTGCAA60SRIBOSOMALPROTEINL7 AACATTGAAAAGTTGTGGTCTGATCAGTTAATTTGTATGTAGCAGTGTATGCTCTCATATtubulin,alpha3;unassigned AGCCTGAGGTGATCTGTGAAAATGGTTCGCTATTCACTTGACCCGGAGAACCCCACGAAAribosomalproteinL17;RPL17 CCTGCAGCAGACGTGCCAGCAGCTTGCGGTCCAGCAGGCACCCTCTGCTCAGCCCACCCCSH3ANDMULTIPLEANKYRINREPEATDOMAINS TABLE5-continued Sequencesidentified TCACCCCTGTCCTGTTGGCCCCAGGCAGCCAAGACCGATGGCTTTGGCCCGTCCTTCCCAunassigned TTTTTCTGCCCCATTTCTCTGCCATTTCAGCCATCTCAGCCTGATCTCTGCCTCCTCAGCunassigned

occur.)oligonucleotideSequences

(Freq. of 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 193634 195179 196668 197340 197808 203100 203566 205747 206302 206528 207955 209706 210420 214925 215764 217100 217443 218894 220741 221390 No./ABI SEQIDProbe No.ID Probe 694 695 696 697 698 699200647 700 701 702 703 704 705 706 707 708 709 710 711 712 713 714 US 2012 /0295815 A1 Nov . 22 , 2012 54

ACGCTTCATCATCTATGCCTTCCCCATGCTCAACATCACGGCTGCCAGAGGCTGCTCCTAasparagine-linkedglycosylation12homolog(S.cerevisiae, TTTGCTTCCTTCCCTGGACGGCCCGCTCCCCGAAACGCGCGCAATAAAGTGATTCGCAGADnaJ(Hsp40)homolog,subfamilycmember CCCCTGACCCTGCCGGAAAGCGAAACTGAGATGCGGGCATTGGGCCCTGGGAAGCGTGGGobscurin,cytoskeletalcalmodulinandtitin-interacting methyltransferasephosphatidylethanolamine;PEMTAACTTTCCTAGGTGATTACTTCGGGATCCTCAAGGAGGCGAGAGTGACCGTGTTCCCCTTN- alpha-1,6mannosyltransferase);ALG12 AGAACATGCTTTCAACATTGGATTGCCAGACAACATTGTAAACTGCAATGAATTTTTGTGzincfingerprotein277pseudogene;ZNF277P AGCAGTACAGCTGCCTCAAACCTTTGGGATTTTCAGAATGACTGACACTGCCGAAGCTGTfamilywithsequencesimilarity103,member symbolnameGene/ RhoGEF;OBSCN CAGTGAGTTGAGATCGCGCCACTGCACTCCAGCCTGGGCAACAGAACAAGACTCCGTCTChypotheticalproteinFLJ40448;unassigned CCACTTGTGCCGGACGCTGTGGCTGGTGGCAGCGGTGCTGCTGGCTCTGCTGTGTTGCACMAS-relatedGPR,memberE;MRGPRE AATGAGCAGATTACGGGCAGGGACGACCTGTCAAAGCGCGGAGTGGACCAAACCTGCACTdedicatorofcytokinesis10;DOCK10 ACATCGGTCCGTCCTGCTTCCAGCTGCTGCAGCGCGCCTTCGCCGCCAAAGCATCCAGCAFXYDdomaincontainingiontransportregulator ATCAACAAGTTTGTGCAGTTCATCCATAAGTACATTACCTACAATGCCCCAGCAGCCATCintegratorcomplexsubunit1;INTS1 4;DNAJC4 7;FXYD7 FAM103A1Al; TABLE5-continued Sequencesidentified TTGTTTCCGGTGGTCTTCCCGTTGTGGGAGCAGGTGGAGGGTGGAGACCTAAACTTTGGGZNF524 CCCCTAGCTCCGTCGGTTCCTTTCTGGTGAGATCCCCAGTGCCTGTGGCACCTGTCACCAunassigned GAGCATTCGCTGTACTTTAAGATACCCATCTTTTTCTTTTTAACCCTAATCTTTCACTTGTOP1P2 GGCTGAGGACACCTCCCCGGCTGAGCAGACCAGCCAGAACTTCACCAAGAGCGCAGGGCTunassigned CACATTTGTACTTGCGGACCAGGA?TGACAAGGGAGCCACTGCCTCTGCCATAATCAGAAunassigned TCCCGCATTATCTCCCTGGACCCTCACGCAGCCCACAAGGCAGCTGTTGGTATCATCCCCunassigned TGGAAGCTTTGGTGCTTTGCTGACCCTGTGACCTGAACAGCCACCCACCTCTCCGAGCCCunassigned ACAGACCCCATTCTGCCCACCAGAACCGGAAGTTGTGTCTTTGCAAAAGCAACCAGTTAGunassigned AGGTTGTACGAGTAAGAGGACACTATAAAGGTCAGCAAATTGGTACAGTAGTCCAGGTTTunassigned

occur.)oligonucleotideSequences

(Freq. of 10 10 10 10 10 10 10 10 10 10 20 20 20 20 20 20 20 20 227738 227872 230395 234988 236556 384551 397748 539274 700282 712642 714371 104157 107398 109372 112798 115349 118257 122089 125079 No./ABI SEQIDProbe No.ID Probe 715 716 717 718 719 720 721 722 723 724 725 726 727 728 729110171 730 731 732 733 734 US 2012 /0295815 A1 Nov . 22 , 2012 55

CACCTGACCAATCAGAGAGCTCACTAAAATGCTAATTAGGCAAAAACAGGAGGTAAAGAAendogenousretroviralfamilyw,env(C7)member1 CATCCGAGCTGGGACTCTAATCATGGCTCTGCATGACTCTTCCGATTACCTGCTGGAGTCLAG1homolog,ceramidesynthase2(S.cerevisiae); CCTGTGGTCCATTGTTCATTTTAATTCACATTTCTTATGAAGTATGGTAACAGGGAGGGAglycerol-3phosphatedehydrogenase1like;GPD1L subfamily,betamember2;KCNAB2 CACAATGATTAATCCAGTGCCGCCTGGAGGCAGCCGGTCCAACTTCCCGATGGGTCCCGGsinglestrandedDNAbindingprotein3;SSBP3 CAGATGCTTTTCTCAAACTTTCCTGATCCTGCAGGCAAGCTAAACCAGTTCCGGAAGAACsimilartobeta-1,4mannosyltransferase;unassigned CTAAGCTGCATTGAGAAATGACTCGTCTCTGTATTTGTATTAAGCCTTAACACTTTTCTTmicrotubuleassociatedmonoxygenase,calponinand LIMdomaincontaining3;MICAL3 GCCGGGCCCACTCCATTCAGATCATGAAGGTGGAGGAGATCGCGGCCAGCAAGTGCCGCCsimilartoribosomalproteinL18a;unassigned GGCTGCCTGCATGCACGGTGCCCTCCTTGCACTCCGGACGTGAGCATTCGCAGTGGGTTTchromosome4openreadingframe23;C4orf23 GGGATTTTGGCCTTGTTGACCCTCCTAGGTGCCCTGGGAATTGCAAACAGCTTTCTGGATmicrosomalglutathioneS-transferase2;MGST2 GTCCTGGATGTTGATGTCCTGCATCTAACGCGGTGTAACCCCCGAAGCCGAGCGAGCTCCsplicingfactor3B,14kDasubunit;unassigned GTTATCAAGGACATTTAAGGAATCCTGATCCTCAGAACTTCTCTGGGACAATTTCAGTTCproteasome(prosome,macropain)subunitalpha TATTCCAGAAGGCTCCACCCTGCCGTCCTGCGGGAGACTGCTGTCCAGTCCTGGCCGGGCpotassiumvoltage-gatedchannel,shakerrelated Genename/symbol ERVWE1syncytin);( PSMA55;type, LASS2 CCGAGGGCATTCACACGGGCCAGTTTGTGTATTGCGGCAAGAAGGCCCAGCTCAACATTGribosomalproteinL8;RPL8 CTGGTGTCCAATCTGGATTTTGGAGTCTCAGACGCCGATATTCAGGAACTCTTTGCTGAATHOcomplex4;THOC4 GACTGTATTTACCAAGTCTCCCTATCAGGAATTCACTGACCACCTCGTTAAGACCCACACribosomalproteinS2;RPS2 GCAGGCCTTACCGCTCTGTTTATAGTGACCCACCCTAGATCTTCCCCAAGAGGGACTGGGpaxillin;PXN GCTTCCCCTCTCTCCGGTCTGTCCCTCCAAGATGACAAAGAAAAGAAGGAACAATGGTCG40SRIBOSOMALPROTEINS26 GTCAATCCAAGGATCCAGAAGGCTTATGAGTATTTTATTATCCTGTCCAGGACCCTGAAGFAMILYNOTNAMED TAAAGATACAGTCACCAAGAATGTTTTGAGTTTTTTGAAAGACCCCAATTTAAGCCTTGCcytidylatekinase;CMPK TABLE5-continued Sequencesidentified CACCAAGAGCTCCTGAGCCCCCTGCCCCCAAAGCAATAAAGTCAGCTGGCTTTCTCAAAAunassigned

occur.)oligonucleotideSequences

(Freq. of 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 132753 13323120 133672 135242 137923 144309 146893 150817 156215 163137 168709 170887 174360 179326 180333 183858 184572 187458 188831 192651 No./ABI SEQIDProbe No.ID Probe 735 736 737 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 US 2012 /0295815 A1 Nov . 22 , 2012 56

TCCTATGCAACAAGATCCGATACTTGGACTTATCGTACAATGACATTCGATTTATCCCCCleucinerichrepeatcontaining8family,member TRANSLOCASESUBUNITTIM17 CCCCCTGCCCTCTGACGCTCTCCCAGTACTTCAGGCATATGCTGTGCCCTTGACAGTGGCsprouty-related,EVH1domaincontaining3;SPRED3 Genename/symbol ACAAATGGGAACAGTTGACTGGTTTAGTGGATGCTGAAGGCCTTCAGGAAATATGCTACThypotheticalproteinBC004921;unassigned C;LRRC8C TCTGCTGGCGAGTCCAGAAACATTATTGCCCAGAAGGATTATGTGTTTATGGATTATTTTimportin9;IPO9 TGGTGCGATTCATGGATATACTGGTAAATTTAGGCAAAGTGAAACTTATCAGCGTAGTTTKIAA0157; TGTGGAGCGTTCACTATGGGTGTCATTGGTGGCGGAGTCTTCCAGGCCATCAAGAGTTTCMITOCHONDRIALIMPORTINNERMEMBRANE RIBONUCLEOPROTEIN GGGACTGCCCAGTCTGTGGGCTGTGATGTTGATGGCCGCCACCCTCATGACATCATATAT60SRIBOSOMALPROTEINL12 GACCCATGGCCATGCCCGCCTGCCTGTTACATTCCTGTTATATATAGACCAAGGAAAGCThypotheticalLOC441027;unassigned AACACACGTTTTTAAAGTTCATGTACGTTCTTGTACACAGAGGTAAAGATTTGAAAACCTnucleolarprotein10;NOL10 ACTCTCAGCTCATCTCCCTCAAGCGCCAGGTACAGAGCATGAAGCAGACGAACAGCAGCCRESTcorepressor2;RCOR2 CCTCAGCAGCTCTCCTTGTTACTACTTTTACCAAGCGGAAGATGGACAGCATATGTTCCTringfingerprotein10;RNF10 GAAGTCAAATGCACGCCAACATTCCAGTTTTTTAAGAAGGGACAAAAGGTGGGTGAATTTthioredoxin;TXN TABLE5-continued Sequencesidentified ATGGAGCCTGTGACAATTATAATGGCTATGGCTATGGATTTGGGTCAGATAGATTTGGAAHETEROGENEOUSNUCLEAR TTTTATAAAGCCACAATAGTTAAAGCACTTAGATGTGGACAGAATCGCTTGAACCTGGGAunassigned AGCAATGAGTTGTTTAGTGACACATAGCTGAGAAGTAAAATGACGACAAAAAGCAAGAAGunassigned ACTGTGATCCAAAGCAGCCTAATTACTGGCCGGTCATCCCCCCGAAGTTCTGAGCTCGGGLOC492303

occur.)oligonucleotideSequences

(Freq. of 20 20 20 20 20 20 20 20 20 30 30 30 30 30 196599 199127 207286 208933 229520 236688 690434 696965 705996 102664 108400 113751 114394 142989 145481 160960 No./ABI SEQIDProbe No.ID Probe 755 756 757 758 759 760 761 762 763 764 765 766 767 768 769 770 US 2012 /0295815 A1 Nov . 22 , 2012

GTGGAAAAAGTTGGAAACACAGATCTGTGCAGTTCTACATTCACTGATTATTACAGTGTGcleavagestimulationfactor,3'pre-RNAsubunit1 CCCCACATTGCCCAGCCCTCACACATGGACTGCCCAGTGCCCACACCTGGCTTTGGCAATfucosyltransferase11(alpha1,3) AGGTTACAGACCTGCCTATCGTTCCAATAATCCTGTTTCACTTGAATGAAGGGAGTATGTeukaryotictranslationterminationfactor1;ETF1 TGCTACATTTCCAAGGTGAAGATGTGTGGGCACATGTTATGGCAGATTGAAAAGGATCTCATPsynthase,H+transportingmitochondrialFiATP5Esubunitepsilon; complex , fucosyltransferase);FUT11 ATTTTAATACACGTCATTGGAGGGCTGCGTATTTGTAAATAGCCTGATGCTCATTTGGAAcarbohydrate(chondroitin)synthase1;CHSY1 Genename/symbol TCCTCGCCACCTGCTCGGCTGATCAGACGTGCAAGATCTGGAGGACGTCCAACTTCTCCCGproteinbetasubunit-like;unassigned TTTTGATGGGCTACTCATACAGTTAGATTTTACAGCTTCTGATGTTGAATGTTCCTAAAThigh-mobilitygroupbox2;HMGB2 AATGCACTGGTCACGAAACGTCTAATACTATGACTGTTAAAATGTCAGACTATAACAAATubiquitinspecificpeptidase38;USP38 ACCTCCTATGGCTCAGGATGAGGGAGGCCCCCAGGCCCTTCTGGTTGGTAGTGAGTGTGGjumonjidomaincontaining2B;JMJD2B AGGCACCCCCATGCCATCCCCGGGTCCATTTTGAGCCACAAGACTAGCAGAGACCGTGGCcoiled-coildomaincontaining114;CCDC114 GGAAAAGAACTAAATGAATTCCGGGAAAAGCACAACATTCGTCTCATGGGAGAAGATGAGprefoldinsubunit2;PFDN2 GGAAGCGGTAGACTATAAAAACATTCGTTTCACAGTATGGGATGCTGGTGGTCAAGATAGADP-RIBOSYLATIONFACTOR,ARF 50kDa;CSTF1 AGACGTTTGACAATGAGTCAGTAGCACAAAAGAGATGACATTTACCTAGCACTATAAACCsulfatase2;SULF2 CAGCAGGATAAGCTGATAAAGGAAGGGAAGTACACCCCTCCACCTCACCACATTGGCAAGFAMILYNOTNAMED TABLE5-continued Sequencesidentified TTGATGATACAGTAAGAAACCTGTAAAATTCGAGCCATATAAATAAAACCTGTACTGTTCunassigned GGTCCTCCACCGTCCAAGGCCAGCACACCATTCCTGAAGCCCAGCTTCACACCCTGGATTLOC497256 AATAAAGACCTGATTATACAGGCAGTGAGCTGTAATCCCAGCACTTTGGGAGGCTGAAGCunassigned AAACGAGCAAGGACAGCTCTGCAAATTACTATGCAAGTCAGAAGAAAACATTTGAAATTATRA1P2

occur.)oligonucleotideSequences

(Freq. of 30 30 30 30 30 30 30 30 40 40 40 40 40 40 40 174760 175254 186148 196745 204159 213516 216889 234977 235506 694601 101065 107464 112021 116303 120823 122028 130369 135479 No./ABI SEOIDProbe No.ID Probe 771 772 773 774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 US 2012 /0295815 A1 Nov . 22 , 2012 58

CATTATCAAAATTGGCTTCCAGGCTGTCATGGGCAAGCGAGCACAGCTCCGTGCCAAAGCeukaryotictranslationinitiationfactor2,subunitbeta CTGGGAATGGCAAGGGCAAGGTAGAGTGCCTAGGAGCCCTGGACTCAGGCTGGCAGAGGGATP-bindingcassette,subfamilyA(ABC1)member CAGTGATGATTCAAATGCTGTACAATTAGCCAAGTCTTTAGGTGTTGATTCTCAAATAAAphospholipaseA2-activatingprotein;PLAA CCTTGGGAAGCCCCCTACCCCGCTACCTCTACCTGGCTAGCAACCAGACTAATGCGTGGGamineoxidase,coppercontaining2(retina CGACGCTGGGTCTACTATTGCCTGGTGAACATCACGCTGAGTGACCTGCTCACGGGCGCGendothelialdifferentiation,lysophosphatidicacidG protein-coupledreceptor,6;EDG6 Rad3related;ATRGCAGCGACTACAAGGTGTAATCAAGACTCGAAATAGAGTGACAGGACTGCCGTTATCTATataxiatelangiectasiaand GCCTGCTGTTGCCACACTCCTCATGGATGTCATGTTCTACTCCAATGGAGTGAAGGACCCsimilartooppositestrandtranscriptionunit TGATGGCTGCATGACAGATGTTGGCTTATTGTAAAAATAAAGTTAAAGAAAATAATGTATproteasome(prosome,macropain)265subunit TGCCTCCCTGGTCACCTATTACACCAGTTCTGGAGAAGACATCCTCATTGGCGGCTTGAAlikelyorthologofmouseneighborPunc Genename/symbol A0C2specific;) GGATGAAATGTCAGTGGAAGAAGCAGATGAGAAACTCTTGAGATCTTGGTCCTGTGTTTTGprotein-coupledreceptor44;GPR44 ATPase,6;PSMC6 CGCTGACTTGGAGCCTCTCTTCCTATACCTGTGCAATTCTTCTACGTTTTGTGATCATGCPQlooprepeatcontaining3;POLC3 Stag3;unassigned E11;unassigned 38kDa;EIF2S2 7;ABCA7 CTTCTGGCTGACTGTGCGAAGTATGCTGCCCCACAAGACCAAGCGAGGCCAGGCCGCTCTribosomalproteinL13a;RPL13A GGCCAAGCCAGAACTCCACTATTGCCCTGCCTCCTGTTCTGTCCCCACCATGGCTACAGAgbdef:HypotheticalproteinFLJ46051 GGCCCTCTGGACAGGAGGGACCATCCACTCCATAGCCCTCACCTCCCTTACCATCAAGCTOLFACTORYRECEPTORMOR239,MOR240 TGTTCACTGTCCCCCTAATATTAGGGAGTAAAACGGATACCAAGTTGATTTAGTGTTTTTCD83molecule; TABLE5-continued Sequencesidentified AAAGGAGAGCATCCTGGCCTGCCTATTAGCGATGTTGCAAAGAAACTGGTAGAGATGTGGunassigned AAGCCATCACCTGGATGCCTACGTGGGAAGGGACCTCGAATGTGGGACCCCAGCCCCTCTMEG3 AGAAACATTGAGCATGAACACCATCTGTGCGAGTCATTTACTTATTGCCCCTCACCTCTAunassigned

occur.)oligonucleotideSequences (Freq. of 40 40ccccccTGGTGATGAGGCGC??c???cGTT????ccGTCTCCAGTGCAccGGC???ccc? 40 40 40 40 40 40 40 40 40 40 40 40 40 50 50 50 137092 143330 147381 147942 149034 155915 157784 168528 171369 177184 178151 178477 202425 203782 209426 234929 101692 105293 115081 No./ABI SEOIDProbe No.ID Probe 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 US 2012 /0295815 A1 Nov . 22 , 2012

GCTCGCTCGAGGACCTCAGCTCGTGCCCTCGCGCCGCCCCTGCGCGCAGGCTTACCGGGCglutamatereceptor,ionotropicN-methylDaspartate GGAGCTCAAGAAGCATAAGCCCAACTTCTGATGTGCCAGAAACCGCCCTGAGATCTGCCGvacuolarproteinsorting52homolog(S.cerevisiae); GTCATCTTGGGCAATGAACTGCCAAAATTCTATGATGAGTGAACCTTCCCCAGACTTCTCproteasome(prosome,macropain)subunitbetatype 9(largemultifunctionalpeptidase2);PSMB CCTTCTTCGTGGTGTCTCTGGTCCTCCCCATCTGCCGGGACTCCTGCTGGATCCACCCGG5-hydroxytryptamine(serotonin)receptor1D;HTRID NDUFA7kDa;subcomplex7,14.5 GGGCACTCCCTGCCAGAGGAGACCGTGGACTTCATGGTTCAGCACACGTCGTTCAAGGAGsulfotransferasefamily,cytosolic1Aphenol preferring,member1;SULT1A1 TATCCTGTAGATGTGAAGCACTTTCAGTTTTCAGCGATGTTGGAATGTAGCATCAGAAGCRhoquaninenucleotideexchangefactor(GEF) CACCAAGCTGGAAGGCAGTGATTTAGACCTTTTGAGAATAGGACACTTGGCAGGAGGGAARAD54-like2(S.cerevisiae);RAD54L2 CCTTAGACTTGAAAGTACGGTGGTTGAGGAGAGCAATGGTTCTGATGAGATGGAGAATTCtetratricopeptiderepeatdomain17;TTC17 GGATAACATACAAACCGGTGTGGAAAATGTTGTCCTTTGAGTGGCAAGAATTAGAAAAATzincfingerandBTBdomaincontaining38;ZBTB38 GGGAGAATGTGACCTAATTTATGACAAATACGTAGAGCTCAGGTATCACTTCTAGTTTTANADHdehydrogenase(ubiquinone)1alpha Genename/symbol unassignedgene; CCTAACCCCAGCCTGAAGACCTTCAAGCCCATCGACCTGAGTGACCTGAAGCGCCGGAGChypotheticalproteinLOC348262;unassigned CCTGGAGTAAATATTGGCACAGATTTCATTTGAGAGAACTCAGCCCCCTGGTCTAAGCTGKRAB-Adomaincontaining1;KRBA1 GTGCCCCCTTCTCCCCGGTCCTCCACTACTGGCTGCTGCTTTGGGACGGCAGCGAGGCTGsimilartohypotheticalprotein;unassigned AGGCAGCTAGACCAGGGATAGGAGTGGGCAACTTGCCAAGCCCTTAACTCTACTTCCTCTMASK-4EBP3alternatereadingframe 2D;GRIN2D GTTGTGCTTTATGGCCACTGAGAGAATTCAGAATAAATTGAAAGATGGAGTCTAAAAATTcellcycleprogression1;CCPG1 ATTCAGACAGATTTGGAGATTGGCAAGATTACCAATTTCATCAAGTTTGACAATGGTAAC30S/40SRIBOSOMALPROTEINS4 VPS52 GTATGCAGGTGCCCTCTGTGCCTATTCACAGTTCCCTACTAAAGACTGGAGTGCTCAGCCRIBOSOMALPROTEINS2 7;ARHGEF7 TCATGACCCACAATAGGATACAAACGAAGAGTTTAAGCCAGCATGATCCAGATGGGTTCAhistidinedecarboxylase;HDC TABLE5-continued Sequencesidentified AGTTCACCAGCCCCTCCAGGGAGCACAGCCACGTCTGGTCAGGAATCTTTTAATGAGTGAunassigned

occur.)oligonucleotideSequences

(Freq. of 50 50 50 50 50 50 50 50 50 50 50 50 50 50 50 50 50 50 50 120870 123557 129276 133236 145042 146556 147011 147272 173075 176542 176992 180028 180412 183644 184158 185863 188209 192079 194873 No./ABI SEOIDProbe No.ID Probe 808 809 810 811 812 813 814 815 816 817 818 819 820 821 822 823 824 825 826 US 2012 /0295815 A1 Nov . 22 , 2012

CAAACAAAGCTAAGACAGCAGGGAACAGAATTGTCATGGCTGAATAGACCAATCGTGTTCsulfiredoxin1homolog(S.cerevisiae);SRXN1 CTCCAGGATGCCTCACATTTTCCCTGTTTGTTAGTGGTCTACCCGAGAGTCCTATCAATTtriggeringreceptorexpressedonmyeloidcells-like3 CD96ei AAGTGAGAGCCACGAGCCAAGGTGGGCACTTGATGTCGGATCTCTTCAACAAGCTGGTCAfamilywithsequencesimilarity39,memberD GACCTATACCTGTGTTTCTTGCCTCATTTTTTTCCTTGCAAATGTAGTATGGCCTGTGTCaldo-ketoreductasefamily1,memberBi(aldose homologG(avian);MAFG CAGTTACATCTGCCGAGGCTGCCTCCCTGGATGAGCCTTCCAGCAGCTCCATCGCCAGTAnotochordhomolog(Xenopuslaevis);NOTO CACTGTGCCTGAGACCCTCGACCCAGCCGAATACAACATATCTCTGGAAACCCAGCGGGThypotheticalgenesupportedbyAF044957; FAM39DPpseudogene; HNRPA1P4pseudogene4; ATTGCAAGGGATGGTGCTTCTTTGAGGATGATGTCAATGAGTTCACCTGCCCTGTGTGTTRanBP-typeandC3HC4zincfingercontaining reductase);AKR1B1 Genename/symbol NM_004547;unassigned ATGAACGAACACGGCTACTTTCCAGAGATATTTGATGAAAGGAAGTTGCTTATTCTTCTCtransmembraneprotein77;TMEM77 CATTATGGCTTAATTTATCCATGGGTTCACGTCGTAATATCATCTGATTCTTTAGCTGATHermansky-Pudlaksyndrome3;HPS3 CCATATCCTCACTCTGAGTCTTGGTATCCAGGTATTGCTTCAAACTGGTGTCTGAGATTTDENN/MADDdomaincontaining2D;DENND2D AAGTAACAGGGAAGCTACAGGTTACAACAGATTTGTGAACTCAGCCAAGCACAGTGGTGGheterogeneousnuclearribonucleoproteinAl 1;RBCK1 TGTACCTAGGGAAAAAATTTAAGGAGGTATTCACACTCAGGGTCATGCACTTGCACAATGCD96molecule;C ACATAGTGTATGTTTGTGATATATAAGGTTTTCTTTATTTTGTATATGATCAATAAACCTv-mafmusculoaponeuroticfibrosarcomaoncogene AAAGTCAAGAAAACAACTGGGTCGGATCATGCTAAAAGGAGATAATATTACTCTGCTACASNRPEL1|SNRPE ACTTTTGTGAGGAAGATTAATGTGGCCAATAAAACCTTTAAATGTTAAGTGTCAAAAAAAnucleoporin50kDa;NUP50 CATAGGGCCACAGTGCCGTATCTGCTGCAGACATGATTGTTTCTTGTTCTAGAGGTTTTCMLXinteractingprotein;MLXIP TABLE5-continued Sequencesidentified TTGTCAGCGCCACCTCCACCTTCAGGAGCCTGCCACGTGCCTGCCCTCGGTCACTTAGCCDKFZP434A062 ATGACAAAACAAGGTTCTTTAACACCCCAAAGGTCATACCAGCTCACCAGCAATGGATTCunassigned CCTTCCCCACCATGGCTTCCGGCCCCACCCCGAGTGGCATTGTCGCTGCAGCCAACTTTGunassigned

occur.)oligonucleotideSequences

(Freq. of 50 50 50 50 50 50 50 50 60 60 60 60 60 60 60 60 60 60 207722 218083 220525 234269 236327 264394 343680 421950 101867 106225 114948 126773 129728 130690 137603 138873 141449 152505 162516 No./ABI SEOIDProbe No.ID Probe 827 828 829 830 831 832 833 834 836 837 838 839 840 841 842 843 844 845 US 2012 /0295815 A1 Nov . 22 , 2012

TCCTGACGAGCAGCGGCTGTACAAGGATGACCAACTCTTGGATGATGGCAAACACTGGGtranscriptionelongationfactorB(SIII),polypeptide2 GCAAGTACACGCTGGGCCACTGCACCATCCGCTGGGCCTTCATGCTGGCCATCCTCAGCAlipomaHMGICfusionpartner-like5;LHFPL5 TTAAGTGTGTAGATTGAGCAGGTAGTAATTGCATGCAGTTTGTACATTAGTGCATTAAAApyruvatedehydrogenase(lipoamide)alpha1;PDHA1 CCCTTCCTAGCCTCCTGACATGAGTCTGCTGGAAAGAGCATCCAAACAAACAAGTAATAAchromosome10openreadingframe99;cloorf99 ethanolamine;PCYT2 GGCCTATTTCAGAGAACTGCCGGATCCCCTGCTCACTTACCGGCTCTATGACAAGTTTGCRhoGTPaseactivatingprotein30;ARHGAP30 (18kDa,elonginB);TCEB2 Genename/symbol GAGCTCCTAAGTCACTTCAAGGTGGACCTGGTGTGTCACGGCAAGACAGAAATTATCCCTphosphatecytidylyltransferase2, GGAACCGATTTGTACAATGTGGGAATTTTGTTACCTTTTTAATCAAGGGCAACTTCCTTTzincfingersandhomeoboxes2;ZHX2 TCCCACGGCCCTTCCAGCCTACCCTGGAGGAGATTGAAGAGTTTCTGGAGGAGAACATGGKruppel-likefactor15;KLF15 TTGGGAGAGGATACTGTCCAGAAAATTAATGCATACTTTTGTCACAATTTGCCTTTTTGTWilmstumor1associatedprotein;WTAP TTGTAGCGTGCTTCATGAAAATATCTACTTATCCAGGTTTGCAAATGTACATGTTCATTTIBRdomaincontaining2;IBRDC2 GTTCAATGCCGCACTATTCACAATAGCAGACTTGGAATCAACCCAAATGCCCATCAATGAhypotheticalproteinLOC149157;unassigned AGGGCCCGCAGAGCATTTGGTGCCCCTCCATGTTGCAATGCAAACACCTTCACCACTGGGhypotheticalproteinLOC150223;unassigned GCGTGATTTTCGAGACAATACTGTCAGAGTTCAAGACACAGATTGGAAAGAACTGTACAGF-boxprotein7;FBX07 GCTATTCCCTATATTCAGCAATTAAATCGGATACTTCTGGAGACTATGAAATCACACTCTannexinA3;ANXA3 GTTGGAAAACATGGAAAATGCATCCTTAACACCTGAGCCTCTGGTCATCTTCAGTATTTTsenataxin;SETX GGGATCCACCTCCCAAGTACTCCCCAAATGCACCCCTTAACTAGGAGCAGGGTGTTATTAKERATIN,TYPEICYTOSKELETAL AAGAAAGTGGCTATGGTGCCTGCCCAGGGAAAGCGGTGTTATGACAGGAAGCAGAGTGGC60SRIBOSOMALPROTEINL44 TGGAATGATATCAAAAAGGTCTATGCCTCTCAGCGAATGAGAGCTGGCAAAGGCAAAATGribosomalproteinL4;RPL4 TGCCTGGAGACTCCTATTCACCCTTCAGATCAATATCCCCCAAATAAACTCCCAGTCACTFLJ42957protein;unassigned TABLE5-continued Sequencesidentified GGTTCACCGAGGCTGTGTACAAAGTGTCTTCATGTCCTGTGTTTCACCTTTTAACATACAunassigned TCAGGATTCTGCTGGTCTCTTGCAGAGTGAATGAGTGGCCCCTGCCTCTCCTATGGGTCCunassigned TGTCCCCGGTGCCTGTGAAATTCGTCATGCCATGACCCACCTGCATTAAACCTATTTTTTLOC90120

occur.)oligonucleotideSequences

(Freq. of 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 70 164480 167566 172324 172727 175038 178605 182566 188077 194371 195871 196827 208223 210097 227679 232393 234266 234461 235834 410937 638716 710730 121526 No./ABI SEQIDProbe No.ID Probe 846 847 848 849 850 851 852 853 854 855 856 857 858 859 860 861 863 864 865 866 867 US 2012 /0295815 A1 Nov . 22 , 2012

TCGACAAAGGTAAAGTGGGAGTCTGTGTCTGTGCTCAACCTCTTCACCAGGATCCGGTAAfizzy/celldivisioncycle20related1(Drosophila);FZR1 ATCGCCCAGTTTCTGAGTGACATCCCGGAGACTGTGCCTTTGTCCACTGTCAATAGACAGacetyl-CoenzymeAacyltransferase1(peroxisomal3ACAA1thiolase );oxoacylCoenzymeA- ATGTACCTTCGTTCAAATATCCTCATGTAATTGCCATCTGTCACTCACTATATTCACAAAnucleolarandspindleassociatedprotein1;NUSAP1 CAAGCTGGTGTCCCTCCAGGCTAAAACACTTCCACCCCCTGGGCAGTGCACTACAGGGTGchromosome22openreadingframe26;C22orf26 CTCTGTGAGCTCTGGGCTTCCCAGTTTGTTTACCCGGGAAAGTACGTCTAGATTGTGTGGhematopoieticcell-specificLynsubstrate1;HCLS1 CTGCTCTACTTCACCGGCTCTGCACACTTCAACCGCTCCATGCGAGCCCTGGCCAAAACCpolymerase(DNAdirected),lambda;POLL GCCAAGCCAGTCCCTACTCTTGGGCTGCGGCCACGTGAGGCTCCGCATCAGCAGCCAGGGchromosome16openreadingframe35;C16orf35 GCTAATTAATGAAGAGGAGCAACTACTATTGGTGTATTTTTCACAGATTGGTGCTTTCTAGprotein-coupledreceptorkinaseinteractor2;GIT2 Genename/symbol CCAGAGATGAAGGGAAGTGGACTAAAGTATTAAACCCTCTAGCTCCCATTGGCTGAAGACdualspecificityphosphatase23;DUSP23 CTACCAGACAAGTTACAGCATCGATGATCAGTCACAGCAGTCCTATGATTATGGAGGAAGYipidomainfamily,member5;YIPF5 CTCTTGGAGAACTCCGAGGAGTATGCGGCTCGGGCCCGTCTGCTCACAGAGATCCACGGGubiquitin-conjugatingenzymeE2S;UBE2S TAACCAGCCCCAGTTCCGGGCTGTCTTGGGCGAAGTGAAACTGTGTGAGAAGATGGCCCAeukaryotictranslationelongationfactor1 ATCTCCTCATTGTGCCTTCATCAGAGCTGGTGCCTTCGGGCCAGAAAGACTCTCGTTCTToralcanceroverexpressed1;ORAOV1 CACCATATACAGGAGCTCAGACTCAAGCAGGTCAGATTGAAGGTCAGATGTACCAACAGTTRK-fusedgene;TFG CTGCCTTGTTTTGCGACATTGTCCCATTCACACAGATATTTTGGGATAATAAAGGAAAATphosphoglucomutase1;PGM1 GAGTGATGCTGAACTTAAGGGTTCAGATGTAGATTCTCTGGTCATTGAGCATATCCAAGTribosomalprotein117;RPL17 GCTGTAGACATTATCTGTGTCACCGTGGAAGACTATTTCAACGATTTTGCCAAAATTAAAexocystcomplexcomponent3;EXOC3 GGAGTCCATGTTGCATTTCTTGTGAACTATAAATGGTGCTTCTCATTTTCTGATAATTTThypotheticalproteinFlJ40432;unassigned EEF1Ggamma; TABLE5-continued Sequencesidentified ATAAGGCCCGCTGGAGTCACAAGCCCCATCCCAGACTCTCCAACGCTGGACCTGCAGCGCunassigned CTACGGAAACAAGTTGAAGTACCTGGCTTTCCTCCGCAAGCGGATGAACACCAGCCCTTCunassigned CTGGCAATCGGCTCGCCCTCCTTCCAAGACAAGCTGCTGCTCGGCCCCTCTGAGATCCGTunassigned

occur.)oligonucleotideSequences

(Freq. of 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 124152 126099 126367 128435 131957 133352 140616 151061 151174 153694 153835 155063 155691 165421 169563 172495 173982 176856 189070 197266 No./ABI SEQIDProbe No.ID Probe 868 869 870 871 872 873 874 875 876 877 878 879 880155226 881 882 883 884 885 886 887 888 US 2012 /0295815 A1 Nov . 22 , 2012

TGGCAAGGTACCCGCTGACAGAGAGCCAGCTAGCGCTAGTCCGGGACATCCGACGACGGGnuclearfactor(erythroid-derived2),45kDa;NFE2 TGCCCCTCGGCCCAAGAGTGTCCAGCGGTGGCCCACCTCTTCCTCCCACTACAGCCTCAArequiredformeioticnucleardivision5homologB TTTCTCAGCAACATTTATTCAAGATGATTTTTACCAGGAACCTTATCAAAGGCAAAACCAchromosome5openreadingframe4;C5orf4 CCGTTCTGACCTCTACCTGGACCTTATTAACCAGAAGAAGATGAGTCCCCCGCTTTAGGGregulatorofG-proteinsignalling3;RGS3 GACATGAAAGTTCAGATCCCTTCCACTCAGGATTCTCGCCGCCTTTTCTAAGAAAATAATchromosome10openreadingframe47;Cloorf47 GCGGAGGCTGTAAAACCTGGCACTCTGCTTGGGTTATCAATACTCTGGCTGACCATCGTCnuclearporecomplexinteractingprotein;NPIP Genename/symbol (S.cerevisiae);RMND5B CCCCTGTGAATCAAGATTTGGGCATGTTCTTGGTCACCATTTCCTGCTACACCAGAGGTGBernardinelli-Seipcongenitallipodystrophy2 AAGCGTATTACCCCTCGTCACTTGCAACTTGCTATTCGTGGAGATGAAGAATTGGATTCTH2Ahistonefamily,memberZ;H2AFZ TCTCGGAACCCATCAAGGTGCTGTACTCCAAGTTTCTGATGCACCCGGAGGAGCTGTTTGTFII-1REPEATDOMAINCONTAININGPROTEIN TGTGAACTTGTTGCACTGCAGAAACATATTCAGAGTTTATCTATGTAACTTATTCACTCTfurryhomolog(Drosophila);FRY BSCL2seipin);( ATCCTGTCCCTCACCTCCTCTCCCTGCATCCTCATTGCTCCCTGTGCCTACTTTCCCTCCHUMANUNCHARACTERIZEDPROTEIN TAATACAGCTTAACCTTGCAGCTACCAACTTTTGTGTCAAGCTAGGTACCTTTATTTGATTRANSCRIPTIONFACTORBTF3 GATTCCACATAAAAATTTTCTGAGGTTGTCCTCATTGATCCATTCCATAAAGCTATCAGAribosomalproteinL15;RPL15 AAAGGTGTCCGCAGCCACACGCAAAAAAGAAGATCCGCATGTCACTCACCTTCAGGCGGCsimilartoRPL23AP7protein;unassigned AAGAAGACTCCCGAGGGCGATGCCAGTCCCTCCACTCCAGAGGAGAACGAAACCACGACAPIN2-interactingprotein1;unassigned ACCTGCCCCAGCCAGCGCAGCAGGTTCAAGGCGTTTGTTGCCATCAGGGATTACAATGGC40SRIBOSOMALPROTEINS2 TABLE5-continued Sequencesidentified TCCTTCTTCAGTGTCCTCACATGGGCTTCCTTCCCTTCTCAGCTGATGCCATCACCTGGGunassigned CCAGTGATTCTGCTTCTAACATATTTCAGACATCATTTCTGTCCATTCCCACTACCAGAAunassigned TTTTATGCTAACCATTGTTTCTGTAGTTAAAATTGTTTTCTTGGTGTTATCTTTTCTCAAunassigned AGCTTCTCCCAAGTGGGCGGCAGCAGCAGCTTCCAGGGTGGCCTGGGTGGAGGCTATGGCunassigned CTTCCCTCAGCCTCCTCAGTAGCTGGATTACAGATATGTATCTCAAGAGCACTCCACAACunassigned AAAGAACTAGAAAGAGACAGGGAGAAATTGTTAAGTGGAAGTGAGAGCTCATCAAAACAAunassigned

occur.)oligonucleotideSequences

(Freq. 70 of 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 70 80 80 80 80 80 198543 203594 205836 208543 215759 221081221081 221266 222840 226105 230293 235614 236001 236583 316129 459905 707864 101310 101811 104346 105423 112167 No./ABI SEQIDProbe No.ID Probe 889 890 891 892 893 894 895 896 897 898 899234727 900 901 902 903 904 905 906 907 908 909 910 US 2012 /0295815 A1 Nov . 22 , 2012 64

AGCATGTGTTCTGTGAGGTTGTTCGGCTATGTCCAAGTGTCGTTTACTAATGTACCCCTGNHP2non-histonechromosomeprotein2like1(s.cerevisiae); ACGCGAGGTATAGGCTCCAGACTCCTCACCAAGATGGGCTATGAGTTTGGCAAGGGTTTGzincfinger,CCCH-typewithGpatchdomain;ZGPAT 10homolog(NUT2,S.cerevisiae);MED10 CGCGCCCTTGACGCCCTTCGGCCAGGCCACTGTGTGCCCCTTCTCCGCAGGCGCCGCCCTbasichelix-loopdomaincontaining,classB AGCAAGATTGATAGATTAGAGACGACATTAGCAGGCATAAAAAACATTGACACAAAGGTAchromosome19openreadingframe59;C190rf59 AGGGCAGATGAGGCGCAGGAAAATAGTCTTGGAAATGTTAAATATGATGGGTAAATTAAAmediatorofRNApolymeraseIItranscription,subunit ATGCTTCACAGCCTACCTCACAGGACAGCCCACTACCCCCAAGCCTCAGCTCAGTCACGTtoll-interleukin1receptor(TIR)domaincontaining adaptorprotein;TIRAP CAGCTATCGCAGACCAGCATCCTGTCCCTTGCTGATTCCCACACGGAGTTCTTCGATGCCoxysterolbindingprotein-like7;OSBPL7 CATGGAGACCTTCTTCTACCGCCCCTGTCTTAATAAAGCTGCGTGTTTCACTTCGGCATCU2smallnuclearRNAauxiliaryfactor1-like Genename/symbol ACGCTCTCTGAGAGACCATCCCCAAGCACAGACGTCCAGACAGACCCCCAGACCCTCAAGFXYDdomaincontainingiontransportregulator AGGAGCTGCTACGGAGCCAGCTATATCCAGAGGTGCCACCCGAGGAGTTCCGCCCCTTTCcoppermetabolism(Murri)domaincontaining CAAGTGCTGTTACAACTGGTTGCTGGGAGAATTAAGCTCATCCTCTGTGATTCCACTGGCabhydrolasedomaincontaining10;ABHD10 (granulocyte);CSF3R 109B;CCDC109BCCATTATGTATTGATTTTGCAACTTAGGATGTTTTTGAGTCCCATGGTTCATTTTGATTGcoiled-coildomaincontaining CCCGGCCATCTTCCACGACTTCCGCATGTTCAACTGCTCCTTCCAGTTCTCCCTGGAGAApatatin-likephospholipasedomaincontaining PNPLA1;1 5;FXYD5 ACTTGTGGTCTTCAGGAAAACTACTCAGAATATAATGACTCCTCATCAGTATCATATTGTzincfingerprotein652;ZNF652 NHP2L1 1;COMMD1 ATGGAGTGAGCCCAAAGGTTCGAAAGGTGTTGCAGCTTCTTCGCCTTCGTCAAATCTTCAribosomalproteinL7;RPL7 CAGGACACCATGGGACCCTCCCAGCATGTCTATGCCTACTCTCAAGAAATGGCTCCCTCCcolonystimulatingfactor3receptor 4;U2AF1L4 4;BHLHB4 TABLE5-continued Sequencesidentified ACTTTGTTCCACGCTCCTGCTACTGACTGTCCCGTCCTGGGTCTTATCCCAGGTCACCTTMGC27165 CAACATCCAGGCCAAGATGCTGCCCAAGAAGACTGAGAGTCACCTCAAGGTAAAGGAAAAHISTONEH2A

occur.)oligonucleotideSequences

(Freq. of 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 112734 112771 114791 114917 117844 118417 120515 121491 127964 131247 132240 135922 136206 138517 141824 143400 148862 No./ABI SEOIDProbe No.ID Probe 911 912 914 915 916 917 918 919127770 920 921 922 923 924 925 926 927 928 US 2012 /0295815 A1 Nov . 22 , 2012

CTCTCCAACAAGATGTGGAAAAACCATATTTCCTCCAGGAACACTACACCGCTGCCCCGCtrinucleotiderepeatcontaining6B;TNRC6B CTTCGCCCTTCATGTGGTCCAACCTGGGCATTGGCCTAGCTATCTCCCTGTCTGTGGTTGATPase,H+transportinglysosomal21kDavo GAAAGCTCGGCGAGATGAAGAATCTGTGCGAATCGCTCAGACCAGACTGCTGGAAGAGGAdifferentiallyexpressedinFDCP6homolog GCGAAACTATGCAACAGTTTACATCAGTCATGTGAAGTATTTGTCTAAAACAGAGCAAACRasassociation(RalGDS/AF-6)domainfamily GGCCCCGTCCTATAGCCAAAATCACAGAAATTCATGAGTTTCTACTTGAGTGAGGAAACTGUANINENUCLEOTIDE-BINDINGPROTEING/ GTGCTATGGCCTCATCATCAAGACTTTCAATCCTATCCCAAGTGAAATAAATGGAATGAAinterleukin1receptor,typeII;IL1R2 TCCTTGTCATTGACCTTAGCTAAACCATGGCAATTCATAAATAGAGGAAACATTAATGAAmicrotubule-associatedprotein,RP/EBfamily Genename/symbol subunitb;ATP6VOB GGGCAATATTCTCTGTACATATTAGCGACAACAGATTGGATTTTATGTTGACATTTGTTTfragilexmentalretardation1;FMR1 GTGCCATGGAGTTCACCATCTGCAAGTCAGATATCGTCACAAGAGATGAGTTCCTCAGAAcaspaserecruitmentdomainfamily,member member2;MAPRE2 (mouse);DEF6 GAMMA-10 GTGCTGACGTACCTGCTGCTACCCTGCACACTGCCCTTCGAGTACATCTACTTCCGCAGCpatatin-likephospholipasedomaincontaining GCCCGGCGAGGAGAACGGCAAAGATTACTACTTTGTAACCAGGGAGGTGATGCAGCGTGAguanylatekinase1;GUK1 4;RASSF4 GCTTTCTGTGCCGATAACGCTCACGCAAGCATGGTTAACGTCCCTAAAACCCGCCGGACT60SRIBOSOMALPROTEINL44 GGTGAAAAACTAACTTCAAGTGTCCCTTGTTTGAAATAAACTTAGCAGAGTCACTTTCTAzincfingerprotein18;ZNF18 GTCAGTGAGGTCCCGTGAGTCTTTGTGAGTCCTTGTGTCATCGTTCGGGCACTGTTTTTTPHDfingerprotein21A;PHF21A 11;CARD11 5;PNPLA5 GTTGTGTTCATCAAGCCCACCTTCCCATTCTGCAGGAGGACCCAAGAGATCCTCAGTCAAGLUTAREDOXIN,GRX GTTTGGGTATGCCACCTCAAAATGTTGGAGAAGTGTATGGAGTTGTGAAAGCTTATACAAadenylosuccinatesynthase;ADSS TCTCCAAGGCCCATGAGGATATGACTGCCCTGGAGAAGGATTACAAGGAGGTGGGCATGGTUBULINALPHACHAIN TABLE5-continued Sequencesidentified GCTGCAGAGACTGCCCCAGGCTGAGCCCGTGGAGATCGTGGCCTTCTCAGTCATCATCCTunassigned TATAGCCACAGAAATAAAGGAGGGACCTATATCTGGGACAGTGTCTTCTCAGAAACAACCLOC375251

occur.)oligonucleotideSequences

(Freq. of 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 153388 157638 159466 170501 171691 173522 174637 178413 180376 181930 184098 185831 186009 186061 188218 188497 191839 197179 198352 No./ABI SEOIDProbe No.ID Probe 929 930 932 933 934 935 936 937 938 939 940 941 942 943 944 945 946 947 US 2012 /0295815 A1 Nov . 22 , 2012 66

TTCCACCGTATGGAAAAGGCGCACCCTGAGCCTGGGACCTGGGACAGCTTCCTGGAAAAGsulfotransferasefamily,cytosolic1Aphenol TGAAAGACCGACCATTCTTCCCTGGGCTGGTGAAGTACATGAACTCAGGGCCGGTTGTGGnon-metastaticcells2,protein(NM23B)expressed TGCAAATTTTCCCCGTTTGCCCTACGCCCCTTTTGGTACACCTAGAGGTTGATTTCCTTTserine/threoninekinase24(STE20homolog, TGGCTTCTGAACTGGAATTCTGCAGCTAACCCTTCCACGACTAGAACCTTAGGCATTGGGH2Ahistonefamily,memberX;H2AFX TGTGCAGGGTATCCTGTAGGGTGACCTGGAATTCGAATTCTGTTTCCCTTGTAAAATATTnon-SMCcondensinIcomplex,subunitD2;NCAPD2 preferring,member3;SULT1A3 TTTAAAGAAGGGAGACGAGTGTGAGCTCCTAGGACATAGCAAGAACATCCGCACTGTGGTTutranslationelongationfactor,mitochondrial;TUFM ATCAAAACAAGACAAATGCTGTTCAGGGAAAGAAGTTGGCAAGCTTAATGTTAAACAAAANADH-UBIQUINONEOXIDOREDUCTASE13KDB Genename/symbol TCTCCACACAGAAAATCTTCTTGATTCTATAGAGACTTAATCATGCCTATGGCTTTGAATenoylCoenzymeAhydratasedomaincontaining yeast);STK24 GGGCCCACCTAGCCTTTCCCTGCTGCCCAACTGGATGGAAAATAAAAGGTTCTTGTATTCserinehydrolase-like2;SERHL2 CTCACGATTTATTCCTCCAGGTCTTTGATTGGAGAGAGTAACTTTTTAATTCTGTTGTTTRNAbindingmotifprotein33;RBM33 in;NME2 TTCAGCCTCAGAAATCAAATTTGACAGCCAGGAAGATCTGTGGACCAAAATCATTCTGGCKruppel-likefactor6;KLF6 3;ECHDC3 TTACACTGCACTCTGACCCTGTAGTACAGCAATAACCGTCTAATAAAGAGCCTACCCCCAphosphoglyceratedehydrogenase;PHGDH TGGTTGGATGAAGTCCTTAGTACAGTTGAAAAACAGAGCATTAAAGACTAATCAATTGTTF-boxprotein30;FBX030 TTAAGGGTTTAGATGTAGACTCTCTGGCCATTGAGCATATCCAAATGAATAAAGCATCTA60SRIBOSOMALPROTEINL17 AAGTCGGCTTCGAGCACCCTTCAGTTCCATGGCCAAGAGCCCACTCGAGGGCGTTTCCTCdeoxyguanosinekinase;DGUOK SUBUNIT AGCCCCATCTCCTGAGCAGCACAGACCCTCCCACGGCCACCGCATGGTGAACCTGCACAGKIAA1257; TABLE5-continued Sequencesidentified TGCTCTATACAAATGTATCCATAAAATATCAGAGCTTGTTGGGCATGAACATCAAACTTTunassigned TGTCCCTTTTTCCCCTGATGCAAGTTGTAGATGGAATAGAAGCCCTTGTTGCCGTAGATGunassigned TTCACTGATAAGGAGAGCAAGCGTCCCAAGAACATCCCCATCATAGTCCTCCCCCTCGAGunassigned ACACTCTACTCCCGGTCAAAAGTGGATTGTATATGTCCTCTTTGATGTGATGGTCCCTTTUNCHARACTERIZED

occur.)oligonucleotideSequences

(Freq. of 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 198356 200308 202673 204337 206444 207506 208250 208748 210081 210225 211303 211412 211767 214987 217726 217999 219479 224565 229017 230842 No./ABI SEQIDProbe No.ID Probe 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 US 2012 /0295815 A1 Nov . 22 , 2012

AAAGTGAAAGCTCTGAACAAGGGTGATGCCAACTCTGAAGTCACTGTGTACTACCAGTCAnardilysin(N-argininedibasicconvertase);NRD1 90AAGGGAATGAGGATGATCTTTGGCTGTTGCTGCTCTTTATGAAGAATCTTATTTGTAACTzincfinger,SWIM-typecontaining3;ZSWIM3 AATCACAATTACACCACTTTAGACCCTATGTGTAGCAGGTCACAACTTACCCTTGTGTGTmicrotubule-associatedprotein1lightchain3 AATGACTTGATCATCTGCTTCCTTTTTGAATTTTTAACAGATAGTAAGTAAATTTGGTGGsolutecarrierfamily31(coppertransporters),member specific;ADARAAACTGCTGACTAGGTCATCCTCTGTCTGGTAGAGACATTCACATCTTTGCTTTTATTCTadenosinedeaminase,RNA- AACCATTTTAACTCTCCAGTGCACTTTGCCATTAAAGTCTCTTCACATTGATTTGTTTCCfucosidase,alpha-L2plasma;FUCA2 AACTTCAGCGAGAAAGTGGGAGTTGCCTTTGACCACATGAAGGTCTGCTTTGGAGACTTTelachomolog2(E.coli);ELAC2 4(Arabidopsis);COPS4 Genename/symbol AAAAGCAAGAGAATTTGAGAAGATGAATCAGTCACTACGATTATTTCGGGAAGTTTGCCTcoli);MSH6mutshomolog6(E. AAGCAGCCCTGCCAGCCACCTCCTGTGTGCCCCACGCCAAAGTGCCCAGAGCCATGTCCAsmallproline-richprotein2E;SPRR2E AAGCATTTAAAATATGTAGTTCCCATATATTTCAGGGTCTCTGTGTATTAAGCTAACTCACOP9constitutivephotomorphogenichomologsubunit AAGCCTTGCCCTGGTGTTCTACCAGAAAAACGTCTCCCAATCACCCAGGAAAGCTGTCCAcarbohydratekinase-like;CARKL AAGGAGAATGCCTAAAGTCAAACGAAGCCGGAAAGCACCCCAGGATGGCTGGGAGTTGATBUD31homolog(yeast); AAGTTACTTGGATGGACCCATTGTGCATCTTTTACTGAAAACTGGCTCCCCATCATGTATtripeptidylpeptidaseII;TPP2 beta;MAPILC3B CTGCTTCTAGCATGGTCGGTGGACCTGGGTGTCTGTCTGCACACGTCCTCCAGTGGCCTGBETA1,4MANNOSYLTRANSFERASE CCCAGCCAGTTAAGCACAAAGAAAAATATTTCAATAAAGGATCATTTGACAACTGTGGAA60SRIBOSOMALPROTEINL12 CCTGCCCCTCCTGGGCACCCTGCCCACCAGGTCACCTGCACCTGCTCTGAATAAACTGTGlipocalin8;LCN8 AAGCACAGATTTGACCCAAGCTATTTATATGTTATAAAGTTATAATAAAGTGTTTCTTACCDC-likekinase3;CLK3 AAGTCCGGTCTCTGACCCTTGACTCATGGGAGCCAGAACTAGTGAAGCTCATGTGTGAGCcentaurin,beta1;CENTB1 1;SLC31A1 TABLE5-continued Sequencesidentified GGGCCGCTCGCAGACCAGCTTTCCTGGGAGCTGGCCCCGCTCCCGCGTTCCCCACCCTGCunassigned 80AAGTGTGATGGCATGCACGTGTGGATCACTTGAGCTTGGGAGGTCAGAGCATAATGGCACunassigned GGGACACTGTTGGATAGGAGGCGTGGTCCCAGCGTGGTCTCCCTGTCTGGGCCTCTGCCTunassigned

occur.)oligonucleotideSequences

(Freq. of 80 80 80 80 90 90 90 90 90 90 90 90 90 90 90 90 23515180 235454 236383 264940 541843 100430 101196 101893 103225 104059 105120 105172 10523990 105376 105718 105982 106345 106552 106979 107385 No./ABI SEQIDProbe No.ID 97310419000 Probe 968 969 970 971 972 974 975 976 977 978 979 980 981 982 983 984 985 986 987 988 US 2012 /0295815 A1 Nov . 22 , 2012

transcarbamylase,anddihydroorotase;CAD AGAGCGAGGAGAAGCGAGAAAAGATGAAACGGACCCTTTTAAAAGATTGGAAGACCCGTTregulatorofG-proteinsignalling2,24kDa;RGS2 AGAGCTTGGTTTCATTGAGCATTTCTCTATTTTTCCAGTTATCCCGAAATTTCTATGTATmicrotubule-associatedprotein,RP/EBfamily ACCCTCGCTACAAGCCCGTCCCTGCCCTGGAGAACGACCTCGCGCTGCTTCAGCTGGACGgranzymeM(lymphocytemet-ase1);GZMM ACCTGGGCCTTCTGAACATTCCAAAAGTTTTGACAAGTGGACGACTAAGATTAATGAATGribonucleaseL(2',5'-oligoisoadenylate synthetase-dependent);RNASEL ACTAGGAATCCTCCAACCAGGCTCCTGTGATAGAGTTCTTTTAAGCCCAAGATTTTTTATAPEXnuclease(multifunctionalDNArepairenzyme) ACTCGAATCCAGAAGGAACGATTTGGCTCTACCCAGGAGTACGAAGCTTGCTTTGGTCAGcarbamoyl-phosphatesynthetase2,aspartate AGACCTTGCTCTTCCTAGTCCTTTTAATGCTGTGTGTTCTGTTAAGTTCTTTCATTTGTTTAF7RNApolymeraseII,TATAboxbindingprotein (TBP)-associatedfactor,55kDa;TAF7 AGAGTCATCTCTAGTTCCCCACCTCAATCCCGGCATCCAGCCTTCAGTCCCGCCCACGTGleukemiainhibitoryfactor(cholinergicdifferentiation Genename/symbol member1;MAPREL factor);LIF ACAGACATGTCCTTCGATAACTCCCTGTTTACCGTCTCCGCGAAAACGATGCCAGAAGAAhypotheticalLOC255809;unassigned 1;APEX1 ACTGGAGCCACCCGCGAAAATTCGGCCAGGGTTCTCGCTCTTGTCGTGTCTGTTCAAACCribosomalproteinS29;RPS29 ACTTCTGTTTATTGTGGATGTTAAAGCCAACAAGCACCAGATCAAACAGGCTGTGAAGAA60SRIBOSOMALPROTEINL23A AGACTGTGAAAAGATCCTTGAACGGAAAGCCAAATCTTGCCAAGTAGGAAAGGAAAAGGG60SRIBOSOMALPROTEINL26 AGAGACCCTTTCTGAAAGAAGTATGGCCAAAAGCACTTTAATGCTGCTGACATTGTTGTTmitofusin2;MFN2 TABLE5-continued Sequencesidentified ACGGTGAGGCGGAGGCACTGGCTGCAAAAGTCCACCCCCTCTAGACCTCTGCAACCACAGunassigned ACGTTACCCCACTGTTTCCCACTGCCCGCGACGTCACTTTCCTGTGCACGTTACCCCTTCunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 109365 111545 112240 112953 113098 113335 113678 114207 114676 116246 116401 116549 116793 116850 117096 No./ABI SEOIDProbe No.ID Probe 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 US 2012 /0295815 A1 Nov . 22 , 2012

AGGAATATGCAGAGGAGTTCAGGACCTACCTGGAGGGCGAGTGCCTGGAGTTGCTCCGCAmajorhistocompatibilitycomplex,classIP;HLA-F AGCTACTAGCTGCCTACGTGTGTGCATTTGCTATATAGCATACTTCTTTTTTCCAGTTTCplateletfactor4(chemokineC-Xmotif)ligand AGTTATAATTCCTGCCTCAGAAAAAGCTTTTCCATTACACTGTGAATGATACCTGTTTTGproteindisulfideisomerasefamilyA,member5;PDIAS AGCTTGGAACTTTTGAGATGATCCCTAACATACTGTACTACTTGCTTTTACAATGTGTTANedd4familyinteractingprotein1;NDFIP1 AGGATTATGGGTCCTGCAATTCTACAGTTTCTTACTGTTTTGTATCAAAATCACTATCTTFas(TNFRSF6)-associatedviadeathdomain;FADD AGGGCCAGGGATGCATGGGATTTTAATTGTTTCATCACACCTTCCCCGTGGCAAAGAAACchromosome16openreadingframe57;C160rf57 AGGTCCAGGTAGTTCGAGGACACTACAAAGGTCAGCAAATTGGCAAGGTAGTCCAGGTGTribosomalproteinL26-like1;RPL26L1 ATATTAAAGGCATTGAAGGACATTCACCTGGAAACTTACCAAAATTCTGCCATGAGTGTGchromosome8openreadingframe70;Coorf ATCAGAGACCCTGCCTCTGTTTGACCCCGCACTGACTGAATAAAGCTCCTCTGGCCGTTTGprotein-coupledbileacidreceptor1;GPBARI ATGGACCCCAAGTTCCCGAGGAACATGTGCTTTGCCAAGAAGCAAAACAAGAAGGTCCTAsimilarto60SribosomalproteinL29(Cellsurface heparin-bindingproteinHIP);unassigned Genename/symbol AGCACATTTGCCTACTAATGGAAAAGGTTAATAATTCATGCCAAAAATAGAAATTAGCGTcytidinemonophosphateN-acetylneuraminicacid synthetase;CMAS AGGCTCTGTGAGGCACGAACCCTGCCTCCCTAGGCCGGACCTTGTGGACGACAGCCCCAChypotheticalproteinMGC13114;unassigned AGGGAACAGTGCTTAGAAAAGCAAAAACTAGGTGTGTCATTGAAATAATAGGCATAAAAAhypotheticalproteinLOC54103;unassigned ATCACACTGTCAGAGGCTTACATTCAGATTTGGAAGAGGCGAGATAATGATGAAACCAACubiquitinspecificpeptidase39;USP39 ATCCTGCTGGAACCTCAGCTGCAACATGAGCTCCGCAGCCAGGTCCCGCCTCACCCGCGCplateletfactor4variant1;Pf4v1 AGATATTCTACATCCCATCCACAATACTACTGATTTTAGAGGACAAGACAATAAAGGGATalpha-kinase1;ALPK1 AGCACCTAAGAAGGGCTGCTGGACCTACAGAGCTCATGGTTGGATTAACCCATGCATGAG60SRIBOSOMALPROTEIN117 4);PF4 AGGCACAGTACGGCCTCACCGACGAGGTTCACCAGCTAGAGGCAACCATCGCTGCCCTGAtektin2(testicular);TEKT2 AGTCCCTTAGCCATTATCTGAGAGGCTAGAATTCTGGCAGTGTCCCCGTGCATCTTTCCChypotheticalproteinFLJ14107 ATGATAAACTCTGTAAGGAAGTTCCCAACTATAAACTTATAACCCCAGCTGTGGTCTCTGribosomalproteinS25;RPS25 ATGGAGCTGGCCTGCAGCCTTTTTGTGCAAGTGGGAACGCCACTGTCCCCCTGCTTTGTGSERINEPROTEASEINHIBITOR,SERPIN TABLE5-continued Sequencesidentified

occur.)OligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 117279 117960 117986 119357 119905 120173 120734 120814 121186 121320 121518 121803 122713 123515 124957 125201 125329 125982 127187 127871 127934 No./ABI SEOIDProbe No.ID Probe 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 1018 1019 1020 1021 1022 1023 1024 US 2012 /0295815 A1 Nov . 22 , 2012

enhancerelement-bindingprotein107)(TAXREB107 unassignedproteinC140);Neoplasmrelated-( CACCAGTTGGTGGAGGCTTCAGGGAAGACCAGAGTCCTGGACAGAGAGGGTAACAGGAGGsolutecarrierfamily39(zinctransporter),member CCAACACCTTCTCGCCCGCAAACGTGGACGCCTCCGTGATGTACAGGAAGTGGAAAGAGAcelldivisioncycle34homolog(S.cerevisiae);CDC34 ATGGCTCAAATAATACCCTGGGTATGCAGGACCCACTATACCTTGCATTTGCTGAGTACAproteintyrosinephosphatase,non-receptortype ATTTCCTTATCCATGGAGGAGACCTCTGAACAGATCACAAATGTTACGTGAGCTTTTTCCchromosome6openreadingframe89;coorf89 CAAACATCTTATTGATACTTACTTCAAGAAGAAGAAGCTGTGGAAGCCCAGACACCTGATsimilarto60SribosomalproteinL6(TAX-responsive CAACCTACTACGCACAGTGCTACCGCCACATGCTGGACTTGCAGAAGCAGCTGGGCAGATSH3-domainGRB2likeendophilinB2;GLB2 CACAGAGCATCGTGGAGGCCACCTCTAGGCTTAAGACCTTCAACTTGATCCCGGCTGTTGmitochondrialribosomalproteinL4;MRPL4 CATGCACCTTACAATTTCTGAACAGTTAACCCTATAGAAGCATGCTTTATATGAGTGTCTTNFreceptor-associatedfactor5;TRAF5 Genename/symbol ATGTAGCAAAGCTTTTAGCCGATCCTCAAAACTTACTGAACATAAGATAATTCATACTGGzincfingerprotein675;ZNF675 CAGAGAATCAAGGATTTTTTGCGGAATCTTGTACCCAGGACAGAGTCCTAGTGTGTGCCCcathelicidinantimicrobialpeptide;CAMP CAGCTGTAGCCTATGGTGTGGCCAGCCTCACCCCCAGCAGCAAGCGTGGCTGCCCCCACAscratchhomolog1,zincfingerprotein (Drosophila);SCRT1 CAGTGTTGCAGTGTGAATTCCTAAATAGAGGGTAAAGTGAGCCTAGCCAGGAGGTGTTTGglucose-fructoseoxidoreductasedomaincontaining 7;PTPN7 ATGGGAAGAACAGAATTGCTCCTGCATGCAACTAATTCAATAAAACTGTCTTGTGAGCTGclusterin;CLU CAATTCCACGATGCCAAATTCATGGCAGACATTGATCTGGATCCAGGCTGTACATTGAATthreonyl-tRNAsynthetase;TARS 7;SLC39A7 CACTGGAGGCCTTGTAGGATTAAGGATACCAACATCAAAGGTGTAATCAGCCTCATTGGAadultretinaprotein;unassigned containing5;UBXD5CAGGACGATACACTCACGCTGCAGGCTGCAGGCCTTGTGCCCAAAGCAGCACTGCTGCTGUBXdomain 1;GFOD1 CATCATAGATGACATCAACAGTGGTGCCATGGAATGCCCAGCCAGTTAAGCACAAAGGAA60SRIBOSOMALPROTEINL12 TABLE5-continued Sequencesidentified CACGCAACCCTGGATAAATACGTAATTAAGTCCCGGCGCTCCCACTCCCGGAAAGGACCTuna CAGGCAACTCCGAGTCTGCCCCCGTCCCTGCAACGGGTGACTCTCAGGATGCCCCTGTGCCELP

occur.)oligonucleotideSequences a

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 128131 128174 128456 130150 130721 131361 132592 132917 133345 133818 134295 134910 136062 136254 136396 137251 137826 138381 139445 No./ABI SEOIDProbe No.ID Probe 1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 US 2012 /0295815 A1 Nov . 22 , 2012 71

CGTCCCAAATCAATAAGAAGGTAGAATGAGTTATGAGTTATTCATATTCTGTTGGAAGCTcyclin-dependentkinaseinhibitor2D(p19,inhibits regulatorofchromatin,subfamilyacontaining CCACAACTACCAGATTGTCAATCATGACCAAAAGTTGCTTCTCATCACTTCTACAACCCCkelchrepeatandBTB(POZ)domaincontaining CCATCCTTCCAGCTATCCTGCAAAGTGCAGCCCTTCCATGTTGCCCTGAAAGTCCCAGATsolutecarrierfamily2(facilitatedglucosetransporter CCATTTAGTCACCTAGGCCAAAGTCCGGAAGGATGCTCCTCTTACACTTTTCCGAAGATAperoxisomalD3,D2-enoylCoAisomerase;PECI CCTCCACTGCTTTTCTATGGGAGACACTCTTAATTTAACAGATGAGAATATTTTGAAACTmethyl-CpGbindingdomainprotein6;MBD6 CCTTGCCCACCTCACTCCTGAGTTAGCACACTTTCCAGGTGTCAGCAGGTGTGATCAGGGfamilywithsequencesimilarity128,member CCTTGCTATAGAAGACCTGGGACAGAGGACTGCTGTCTGCCCTCTCTGGTCACCCTGCCTdefensin,alpha3neutrophil-specific;DEFA3 CTAATGAAATGTAGTTGGGTTCTTCCTGTAATGCGCTATTATGTCTTGGGCTTAATAAAASWI/SNF-related,matrixassociatedactindependent CTAGCTCCACGGCACGGGTGTCTCCCAGCCACTGCCCTTGCTGGAGGACCGCTGTGAGTCchromosome19openreadingframe25;C190rf25 CGCTGCTGCAACCGGCCGTGTGGCGCGCGCTGCTCCTGGACCGCCGCCAGGCCCTGCCCAundifferentiatedembryoniccelltranscriptionfactor DEAD/Hbox1;SMARCAD1 Genename/symbol member14;SLC2A14 CCGACCGACAGTTCCAGGAGCTCAACGAGCTGGCGGAGTTTGCCCGCTTACAGGACCAGCtransmembraneprotein142A;TMEM142A CCTGGAAATGCCAGAGAAGGATAACACATTCGTCCTCAAGGTAGAGAATGGAGCCGAATASH2Badaptorprotein2;SH2B2 CDK4);CDKN2D CCTTTGAAATATATAGAAGGTGACAAAGCTTTTAACCAGTCCTCAACCCATACTACACATzincfingerprotein486;ZNF486 1;UTF1 7;KBTBD7 CCCTCGGCCTCCCGTTGGTATCTTCCATCTCATGCGTTCAGCATTGTAACCTCGCGGCGGhypotheticalLOC401093;unassigned CCCTGGTAAAGCCCAAGGAAGTTAAGCCCAAGATCCCAAAGGGTGTCAGCCACAAGCTCCPROTEINL2960SRIBOSOMAL B;FAM128B TABLE5-continued Sequencesidentified CCAATATCCAGGATAAGGAAGGCATCCTCCCCGACCAGCAGAGGCTCATCTTTGCAGGCAUBIQUITIN CCCACTGGCTTCAAGATGGCATTAATTACTAGCCTCCCACTGTGGTGCCTGGCAGAGACCunassigned CCCCAGAAACCGAATCCTCTCTTCTGCATCCCCCTCTAAGTGATCTCTCCCAGTCCTGGGunassigned CCCCCTCTAGTGCATAATTCAGCATACGATGAGTATGAGTCTGTTTTGGACCCCATCCAAunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 139760 139869 141545 141908 142255 142977 143723 143967 144226 145606 146482 147338 147346 147541 149070 150159 150872 151419 No./ABI SEQIDProbe No.ID Probe 1044 1045 1046 1047 1048 1049142775 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 US 2012 /0295815 A1 Nov . 22 , 2012

formyltetrahydrofolatecyclo-ligase);MTHFS GAAGGTTCTGGCTCCACGGGTGAATCTGACTTTTCGTAAAATTTTGCTTACTAAAAAATAalkB,alkylationrepairhomolog2(E.coli);ALKBH2 CTCCCACCTCACCGTTTCCATAGTTGGCTCTTTTGTGTCATCTTACCCTTTACAGAGAAAhexamthylenebis-acetamideinducible2;HEXIM2 CTGGAGAGACAGATCTGAATGTTCAGTTCTAGCCAAGGTAGATTTTACTTTCAACTTTTTproteinphosphatase1,regulatory(inhibitor)subunit cytidylyltransferase)2;CDS2 GAAGTGGCTCTTGCAGCTAGAGTTGACTCAGAAGCCGAAATTCCTAGAAATCAGGTTTCTegf-likemodulecontaining,mucinhormone CTTTCTCTGTTTAGCAGTCACAGGTGAGGGTGGTATTAGCATCTTTTTTATGTAGAAAAAactivatorofbasaltranscription1;ABT1 GAAATATTCCAAGGCCTGGATGCTAATCAAGATGAACAGGTCGACTTTCAAGAATTCATAS100calciumbindingproteinA12;S100A12 factor1;AIF1GAAATGGCGATATTGATATCATGTCCCTGAAACGAATGCTGGAGAAACTTGGAGTCCCCAallograftinflammatory GAAATGTGTCCTGAGAATGGATCTTGTGTACCTGATGGTCCAGGTCTTTTGCAGTGTGTTchromosome2openreadingframe28;c2orf28 GAACATGGAACAGAATGAACAGAAAGAGCAGAAGTCAAGTGAGCTCATGAAAGAAGTTCCleucinerichrepeatcontaining37B;LRRC37B EMR2like2:receptor- Genename/symbol CTCAACCAGACAAATCAGGGCTGCCCAGTGATCGGTTCTCTGCAGAGAGGCCTGAGGGATT-CELLRECEPTORBETACHAINVREGION CTGCAGCTGTTCAAGCACGAGATGCAGCATTTCGTGAAGGTCATCCAGGGCTACATCGCCtubulin,gammacomplexassociatedprotein CTGCCCCCTGGACCTCTTCTACAAGTGTGTCTGCTTCCTGCCTGTGAAACTCATCTTCGTtransmembraneprotein38A;TMEM38A CTTCTATGACGAGAATGATGCCAAACTCTTTGAACAGATTTTGAAGGCCGAGTACGAGTTcalcium/calmodulin-dependentproteinkinase GAAGCTTGAGCCTAAATCTGGCTGGATGACTTTTCTAGAAGTTACAGGAAAGATCTGTGA5,10-methenyltetrahydrofolatesynthetase( 6;TUBGCP6 2;PPP1R2 I;CAMK1 CTTTGACTGCCAGTATCTGATGGCCACCTTTGTCAATGTATACATCGCCAGTTTTATCAGCDP-diacylglycerolsynthase(phosphatidate

TABLE5-continued Sequencesidentified CTGCCCCCAAGACACTGTGTGTGACCTGATCCAGAGTAAGTGCCTCTCCAAGGAGAACGCgranulin;GRN

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 151826 152585 154789 154932 154937 155553 157712 158606 158656 159602 159687 159695 159877 160727 160921 161035 No./ABI SEQIDProbe No.ID Probe 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 US 2012 /0295815 A1 Nov . 22 , 2012

3

GACTTGTATGCTGAACTCCGCTGCATGTGTATAAAGACAACCTCTGGAATTCATCCCAAApro-plateletbasicprotein(chemokineCX—çmotif) acetylglucosaminyltransferase);OGT GCCAGTTGGCTGAAAGGTTTGAAATACGTACCCCAGTAAAACCATTCAATCAATAATTGGubiquitin-conjugatingenzymeE2W(putative);UBE2W GACTGAGCTGTTTATTTTCTTCACTTCCCTTATGCAAAAATTTACCTTCAGGCCCCCAAAcytochromeP450,family2subfamilyJpolypeptide GACTGTGGACCTCATGGTTGAGCACACGTCGTTCAAGGAGATGAAGAAGAACCCTATGACsulfotransferasefamily,cytosolic1Aphenol preferring,member2;SULT1A2 GACTTCACTGGAAACAGCAAACTGGAGCTGAATTTCAAAGCTGGAGATGTGATCTTCCTCneutrophilcytosolicfactor4,40kDa;NCF4 GAGCTGGACACCCCCTCTATGACTGCAGAGCAAGTAGCTGCCATTGAGCAGAGCGTCAATalanyl-tRNAsynthetasedomaincontaining1;AARSD1 (UDP-Nacetylglucosamine:polypeptide STATIPIprotein1;interacting GATATAGATTGTCCGGCCGCTTTGTGATTCCATGGATTGATTCAGTCTTCTGGATTTTTTO-linkedNacetylglucosamine(GlcNAc)transferase CMTM5containing;5 GCAGTGAGATCCCAGGAAGCTGGCACATCTTGGAAGGTCCGTCCTGCTCGGCTTTTCGCTbonemarrowstromalcellantigen2;BST2 GCCACTGCCGTTCCTCTATGTGCTCCTGCCCGCCGTGTACTCCGGGATCTGTGCTGTGGGneuropeptidesB/Wreceptor2;NPBWR2 Genename/symbol GAATGTTGAAGGATTGAAGAGTTCTAAGCATAAAATAAGTGGCATTTTCTGACTTCTTCCtumorproteinD52-like2;TPD52L2 GACCAAGATGATCAGAAACCTGGCCCCTCAGAGCGATCTCGAGCCACAAAGTCAGGAAGTscaffoldattachmentfactorB;SAFB GACGGGCCAGCCCAGGAACCCCAGAGCGCACCATGGCTGTCCAAGTCCTCTGTCTCCTCTrhomboiddomaincontaining3;RHBDD3 protein;unassigned ligand7);PPBP GATCTCTCTGTGACTGACTTTGTGACTGTCCTGTGGTTTCTCCTGCCATTGCTTTGTGTTmajorfacilitatorsuperfamilydomaincontaining GATTCTTCAGAGGTTAGCCTGGTACTTTCTCATCAGACACTAGCTTGAAGTAAGAGGAGAprenylcysteineoxidaseilike;PCYOXIL onGCCAAAGTCATACACTGGCTATCAGAAAATTATGCTGGAAGAATTGCAGTGGAAAAACTGsignaltransducerandactivatoroftranscripti 2;CYP2J2 GACTGCCAGCGTGGTACCTCCCATGCTGCAGGCCTCCATCTAAATGAGACAACAAAGCACEGFR-coamplifiedandoverexpressed 5;MFSD5 GCAAGCCTCCTGCTTCACTTTCAGGTTTCTCGAAGTGCCTTCTTGCTCCTGTCTGTTTCCCKLF-likeMARVELtransmembranedomain TABLE5-continued Sequencesidentified GAGGGATTAAAGATAAAAATTTTGGCTGGATGCAATGGCTCACGCCTGCTATCCCGCTATunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 161406 162153 162796 163054 163084 163151 163194 163252 164529 165048 165825 166173 166964 167507 168872 169477 169779 169988 No./ABI SEOIDProbe No.ID Probe 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 US 2012 /0295815 A1 Nov . 22 , 2012 74

GGCACAATGCGGTCCAGACCCTGCTGCGTCTCCCTTCCAAACTCTGGTGCTGAATAAACCglycoproteinIb(platelet),betapolypeptide;GP1BB GCTCCATTGGATCAGCTTCCCAGGAAGTTCAGCTTCGGGTTAGTACATAAGGCCACCACAchromosome10openreadingframe33;cloorf33 homolog(S.cerevisiae);TIMM50 complex,subunitG;ATP5L TRANSLOCASESUBUNITTIMS GCTGGTCACCTACCTGCTCCCTCTGCTGGTCATCCTCCTGTCTTACGTCCGGGTGTCAGTprolactinreleasinghormonereceptor;PRLHR GGCATCATTGGCTATGATGTTTGAAGACCAATCTTTAACATCTGATTATATTTGATTTATATPsynthase,H+transportingmitochondrialFO (sulfamidase);SGSH Genename/symbol GCCCATGCAACTCAGTCCAGGATTTTACTGGGTCAGTGACATTGGTGGAAGCCTTCATGCGprotein-coupledreceptor68;GPR68 GCTGCATCCCGCGTCCAGCACCTACGTCCCGCTGCCGTCGCCGCCGCCACCATGCCCAAGhigh-mobilitygroupnucleosomalbindingdomain GGAAGACCGCTATAAAGGCTGAATGATGGATACATTATTCCTTCACACAGTGGATTTTGAPOlooprepeatcontaining3;POLC3 GGATATTTCATGTCTGAATCGGGACCCAGCTCGAGTAGTAGTTGTGGACTGCAAGAAGGAtranslocaseofinnermitochondrialmembrane50 GGCATACAAGGCGCTCCTCAGAGTCAAACACTTGATGCTTTTGCATTATGAGATTTTTGTGTPase,IMAPfamilymember5;GIMAP5 GGCCCCGAGGGCACGGAGGACGTTTTCACCTTCGGCTTTCCAGTACCGCCCTTCCTGCTGproteinphosphatase1,regulatorysubunit GGGAGACGTTCAGCTACCCTGACTTTCTCAGGATGATGCTGGGCAAGAGATCTGCCATCCallograftinflammatoryfactor1;AIF1 GGGAGTAAAAACAGGCTGGTGCAGACAGCAGAGCTCACAAAGGTGTTCGAAATCCGCACCgliamaturationfactor,gamma;GMFG GGGAGTGAAATGTTACCCAATTAGGCTTGTCAGGTTAGTAATAAACTGAACAGTAATAAAtripartitemotif-containing23;TRIM23 GCCCTGGCAGAAGACATCGAGAAGACCATGAGCACGGCTCTGCACGAGTTGCGGGAACTCSLIT-ROBORhoGTPaseactivatingprotein SRGAP3;3 GCCTGGACTCTTGCACTGAAAATTGTCTCTCCAGCTGTGTAGACCACTTCATTGACACCAMITOCHONDRIALIMPORTINNERMEMBRANE GCTATCTGACCCCTGACCTCTGGAAAGAGACTGTATTTACCAAGTCTCCCTATCAGGACTribosomalproteinS2;RPS2 2;HMGN2 GGCCCACTTTGTAGCCCCATCACCCTTGGCCTGCTGGTGGCTGGCGTCCTGGTTCTGCTGCD8bmolecule;CD8B 3D;PPP1R3D GGCGATGCCCGTCCTCTGGCTTGGGTTAATTCTTCGGTGACACTGGCATTGCTGGGTGGTN-sulfoglucosaminesulfohydrolase TABLE5-continued Sequencesidentified GCCCCGGCCCCTGCAGCCGCAGAGATGTTGATGCCTAAGAAGAACCGGATTGCCATTTATunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 170312 170400 170630 171390 172691 172942 173555 173918 175144 177061 177639 177981 178007 178355 178408 178825 180037 180184 180191 No./ABI SEOIDProbe No.ID Probe 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 US 2012 /0295815 A1 Nov . 22 , 2012 75

GGGATCTTGGTGCTGAGCCGCCACACCCTGGGCCTGGCCCTGCGGGAGCACCCTGCCCTGproteindisulfideisomerasefamilyA,member2;PDIA2 GGGTCCCATTTCTCACTGAGAAGATTGTGAATATTTCCATATGGATTTTCTATTGTTACTsolutecarrierfamily2(facilitatedglucosetransporter), GGTCCTCAAGGAATCAAAGTTTAAGGAAACAGGTGTAATTACCCCAGAAGAGTTTGTGGCATG3autophagyrelated3homolog(S.cerevisiae); GTCCGTGTGCTGGATGAACGCCTGGTTCGACTGCGTGATGGTACCCGGTCTTACTTCGGGtumornecrosisfactor(ligand)superfamily,member GTGCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAGCTCTGAhematologicalandneurologicalexpressed1;HN1 GTGTCTTGATGACTCTCCCAGGAATCAGAAAGATAGTATTTACTAAAGAAACGGTTGTTTWDrepeatandFYVEdomaincontaining2;WDFY2 GTGTTACTACAAGATGGCAATAAATACTATGGGATTGTTTGTATTAAAAAATTTACATTGsmallnuclearribonucleoproteinpolypeptideE;SNRPE TACAATGTCTTTTAGCTAATTCTAATTAAAAATTACAGACTGGTGTACAAGATACTTGTGubiquinol-cytochromecreductase,Rieskeironsulfur DPM2subunit;regulatory2, GTAAGCCGAAAGGATGAAGAGTTAGACCCCATGGACCCTAGCTCATACTCAGACGCCCCCpolyglutaminebindingprotein1;PQBP1 GTGTGCTCTGGCTCGGATAAGAGATGGGACATCATTCAGTCACTAGTTGGATGGCACAAGtranslocaseofoutermitochondrialmembrane7 homolog(yeast);TOMM7 GTTCAGTTATGAGGAGTCAAATCCTAAGGATCCAGCGGCAGTGACAGAATCCAAAGAGGGhistocompatibility(minor)13;HM13 polypeptide1;UQCRFS1 Genename/symbol protein;GHITM member3;SLC2A3 GGGTGATTCTCTTGCCATTCATCGACAGTCAGCATGTCATCCACAAGTATTTCCTGCCCCdolichyl-phosphatemannosyltransferasepolypeptide 14;TNFSF14 TAAGAGGACACAAATGAGGACACGTGGCTTTTATACAAAGTATCTATATGAGATTCTTCTringfingerprotein1;RING1 TACACAGCCCCGTGAACCCTGAGGAGTGGAGTCATACACGAAGGGCGTGTGGCCATCGTGbromodomaincontaining9;BRDO GGGCAGATATGCATTAAATAGTTTGTACAAGCAGCTTTCGTTGAAGTTTAGAAGATAAGAgrowthhormoneinducibletransmembrane ATG3 GTTCCTTGTGGATGTTAAAGCCAACAAGCACCAGATTAAACAGGCTGTGAAGAAGCTCTA60SRIBOSOMALPROTEINL23A GTTGTCCTGAAGTCGGGCTCTCCCGGCCCTGCCTCCCAGCAAGTAAGCAAGCTCTTTTGGFLJ45445protein;unassigned TABLE5-continued Sequencesidentified GGGTATAATCTCACAAATCGATGGGACTGCAAGGATTGTAAACTGAAATGAACATGATTAunassigned GGTTTGGAGATCCAGGAACACACAGATTTGGGTATCAAATGTGACCCATGCATTOGTATCunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 180247 180941 180998 181105 181758 182820 183013 184495 185825 186996 187070 187155 187598 187762 188191 189793 189818 No./ABI SEQIDProbe No.ID Probe 1116 1117180427 1118 1119 1120 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132189240 1133 1134 US 2012 /0295815 A1 Nov . 22 , 2012 76

TCAGATGATGACTGGTTGAAGAAGTTTTCTGGGAAGACGCTTGAAGAGAATAAAGAGGAApeptidylprolyiisomeraseE(cyclophilin);PPIE yenininhibitor1;RNH1 TATGTCAAAAATTGGACAAAAGTTTCTCAATGATTAAGGAGGGTGATTATAACCCCCTCTselectinL(lymphocyteadhesionmolecule1);SELL TCAAACGCAGAAGGACTGCCTCACTGAGCAACCAAGAGTGTCAGTTGTACCCGAGGCGTTsmallnuclearribonucleoproteinpolypeptideN;SNRPN TCTCAGTTACAACCTATTACATATGGTCCTTCACATTCAGGGTCTGCTACAACAGCTTCCnuclearfactorofactivatedT-cells,cytoplasmic calcineurin-dependent3;NFATC3 TACCAGTGACCATATTGAAACGCTGTATGAGCTGGACATCGAGTACTCTCAAGTTTTAGCferrochelatase(protoporphyria);FECH TATTCGAAATCTCAGGACTCTTCTGGCCGTAGGTTCCAGGAAAGCTCGTGGAAGCTTTGGsimilartoHESBlikedomaincontaining2;unassigned TCATCAAGTCAAAAGCACTGAGTGTTTTGCTAGTCTAGTGACATGGGTTATTGTATTTCCchromosome20openreadingframe177;C20orf177 TCTCCAGTTGGTTATCTGAATAGTGTCACCAATTCCACCAAGACAGTGCTGAGATTGGAAtransforminggrowthfactor,betareceptorIII (betaglycan,300kDa);TGFBR3 Genename/symbol TACCTGCCTGTAGACAAGTCTCTCTCATACCAACAGAACTTCCGGTACTTCCAGAACCAAgolgiapparatusprotein1;GLG1 TACTTTTAGCCTGTGTCAAATGTAAGTCCCAAGTATTTCCAGCAGGAAGTAATGTCTTCCHSPB(heatshock27kDa)associatedprotein TATGCCAGAACCCCCTCCATCGTCTACGTTATCTGCATCACTTCCAGGTCCACCCTTTCThypotheticalproteinFLJ25006;unassigned TCAGGAGCGCATTAACTGCCTGGAAGGGACCCACGAGTTTTTTGAGGCCATTGGGTTCCAUBXdomaincontaining1;UBXD1 TACCCAGTAACTGAAAGCCCCTCTGGTCCTCGCCAGCTATTTATTTCTTGGATATTTATTinterleukin27;IL27 1;HSPBAP1 TATCACCCTTTACTGCAACCACAGGAACCGAAGACGTGTTTGCAAATGTCCCCGGCCTGTCD8amolecule;CD8A TCATCCTCACTCAGTTCCCTGGTAGCACAGACTGACAGCTGCTCTTGGGCTATAGCTTGGKIAA0913; TCCCGTCAGGACGTTGAGGACTTTTCGACCAATTCAACCCTTTGCCCCACCTTTATTAAACD14molecule; TABLE5-continued Sequencesidentified TCACTCCGCGTCCCTACTGCACCTGTCACAAAGTGCCTTCTGATATGCCTGGCAAACCAALOC150166 TCCGCTTATTTCTGCCAGTATATTTTGGACACTTTATAATCATTAAAGCACTTTCTTGGCribonucleas TCCGGGCTGGGTAAGCTTAGACAAGCCCCCTCCCCTCTCTGTGAGCCTGTTTCTCTGGGAunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 190155 190198 190344 190833 192340 192488 192673 192931 193802 194079 194352 194700 194779 196141 196409 196448 198298 198391 No./ABI SEQIDProbe No.ID Probe 1135 1136 1137 1138 1139191960 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 1153 US 2012 /0295815 A1 Nov . 22 , 2012

monooxygenaseactivationprotein,beta TGCAGATGCTCTTAAAAGCATTGATAACCTTTGTGACGAACATAAAGAGATCCTTAAATTNADHdehydrogenase(ubiquinone)Fe-Sprotein1, TCTTGTTTTTCCACTACTGCTACCACAACTATATTATCATGCAAATGCTGTATTCTTCTTsignaltransducerandactivatoroftranscription1, TGAGGCTGCGGACAAAGCCCTTTCATCTGAGGACTTTCATCTGTGCATATCACGGCCCCCDEAH(Asp-GluAlaHis)boxpolypeptide38;DHX38 75kDa(NADH-coenzymeQreductase);NDUFS1 transcriptionfactor1;BACH1 TGCCGGGCTTTATCGCTGCCTCTATTATAAGCCCCCTGGATGGTCTGAGCACAGTGACTTleukocyte-associatedimmunoglobulinlikereceptor Genename/symbol YWHABpolypeptide; TGCAGTAGACGATACAGGTTGCATGTGGACACTCAGTCACATTAACAACTTGGGAAAAAABTBandCNChomology1,basicleucinezipper TCTCCCCAGGAATTCACTTAAAAAGGGA?TGAGCATTGTGTCAACCTGTTGCAGTGTTTTankyrinrepeatdomain13A;ANKRD13A TCTGTAGAGATGGCCTTTCACTTGAGGAGTACTCAGTTTTCAGGTTCTTCCTAGCTCGGGtyrosine3-monooxygenase/tryptophan5 TCTTCGCCTTCCACTTCTACCGCTCACTGGTCAGCCATAAGACCGACCGACAGTTCCAGGtransmembraneprotein142A;TMEM142A 91kDa;STATI TCTTTTGTCTTTCCGTGGAGCTGTCGCCATGAAGGTCGAGCTGTGCAGTTTTAGCGGGTAribosomalproteinL24;RPL24 TGAAAAAGCAATGACAAATCACTGCAAGAGTACACGTCATAAGCAAAATACTGAGAAATTzincfingerprotein638;ZNF638 TGAAGAAAGTTGAAATCAGCCAGCAGGCCAAGTACACTTGCTCTTTCTGTGGCAAAACCAribosomalproteinL37a;RPL37A TGCCCTGGACCCTCGGCTGGGTAGCGCCACCAGAGCGACCAAACGTCCCGCGCCTTCCAGsorbitoldehydrogenase;SORD TGCCGGAAAATTGGTCGCGATTGTAGATGTTATTGATCAGAACAGGGCTTTGGTCGATGGribosomalproteinL14;RPL14 2;LAIR2 TABLE5-continued Sequencesidentified TGACGC???cTGTICTACACAGccc?ccTGGTCTICAGTGcccTGGGAAACATccTTGccunassigned TGACTGCCCCATATTTTACATCCCTCATTCAAGGTACTGGCTCCTGTATCACCCAGCTCTunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 198428 199360 199779 200004 200160 200186 201343 201440 201912 202982 203098 203648 203700 203708 No./ABI SEQIDProbe No.ID Probe 1154 1156 1157 1158 1159 1160200578 1161 1162 1163 1164 1165 1166 1167 1168 US 2012 /0295815 A1 Nov . 22 , 2012

TGTCCTTCCCGTCAGCCTGGCATTTGACAAATGTACAGCTTGTTCTTCCAAAGTTCTTGAATG7autophagyrelated7homolog(S.cerevisiae); nuclearfactorofkappalightpolypeptidegene enhancerinB-cells3,p65(avian);RELA TGGAGATGGCGACTAGTGGACAACAGAACAATATTGGAATGGTGGTAATACGAGGAAATAsmallnuclearribonucleoproteinpolypeptideG;SNRPG TGGATGACATGGACATGGACTTAGACAAGGAATTTCTCCAGGACTTGAAGGAGCTCAAGGfibroblastgrowthfactor(acidic)intracellularbinding TGGTGAAGAAGCAGGTGTTTGAGCTACTGGCTGCCCTGTGCATCTACTCTCCCGAGGGCCchromosome14openreadingframe151;C14orf151 TGTACAGTTATAGCTACAACCAGTATTATCAGCAGTACCAGAACTACTATGCTCAGTGGGERNAselenocysteineassociatedprotein1;TRSPAP1 TGTCAGAACTAAGGAATGAATTACAGCGGAAAGATGCACTAGTCCAGAAGCACTTGACAAmediatorofRNApolymeraseIItranscription,subunit MED28cerevisiae):homologS.(28 TTAAGTAAGTTTTTCTCAAATTTTGTTTCAGTTCTAGGTCCCTTGTCACAGCTTGGTTTTtetratricopeptiderepeatdomain14;TTC14 TTCCATCATGGATTCATTACAGCTTAATCAAAATAACGCCCCAGATACCAGCCCCTGTATv-relreticuloendotheliosisviraloncogenehomologA, TTCTGTAATCAAACTGCAAATATTGTCATAACCAACATCCAAAATGACGGCTGCTATATApleiomorphicadenomagene-like1;PLAGL1 TTTACCTCTAGGAGGATTTGCTGAGCTCATGGGAAGTAATGGGCCTCAAAAGTTTTGCATWWdomaincontainingE3ubiquitinproteinligase Genename/symbol FIBPprotein; TGGTCAACTTAGCTTTTAAGCAGACGATGCTGTAAAAACTAACGGCTTCTCTGATATTTARAD21homolog(S.pombe); TGTCTTCGTTAGAAAAGTAAAAATGCTGAAGAAGCCCAAGTTTGAATTGGGAAAGCTCATribosomalproteinS3A;RPS3A 1;WWP1 TGTACAACACTTCTTACTGCGCTGAGATCGCTCACAGTGTTTCCTCCAGGAACCGCGAAG60SRIBOSOMALPROTEINL32 ATG7 TTCATTCTGTATTTTGCCCGCAAAGTTTTAAAGCTTTCATCCACAGTCAGGAATTAAACThypotheticalLOC440248;unassigned TTCGCACTGCTGTCTTTGGCTTTGAGACCTCGGAAGCGAAGGGCCCCGATGGCATGGCCCmajorvaultprotein;MVP TTCTGTGCTGGCTGCTCAGAAGATACCGCATATCTAAGAAGATTGATCACCTCATGTATCPROTEINL1960SRIBOSOMAL TTGATAGAAAACGCTTTGATTGCTCAATCTCTTGGTAAATATGGCACCATCTGCCTGGAG60SRIBOSOMALPROTEINL7 TABLE5-continued Sequencesidentified TGGGCACATTGCTGCTAATTAATCTTCCTAATCTCGTGGGATCACAATATGAATAACAAGFLJ21272 TTCCGCTATTTTGCACCACCTGCCTGGCCCTTATGGGCAACTCAAGGAAGAAAGGAAAGAunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 205425 205686 206696 207077 207211 207673 207692 208079 208310 208491 210085 211683 212069 212354 212904 212939 213466 215143 No./ABI SEOIDProbe No.ID 1181211856 Probe 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 1182 1183 1184 1185 1186 1187 US 2012 /0295815 A1 Nov . 22 , 2012

GTGGTGAAGACAATGCAAGCCCTGGAGAAGGCCTACATCAAGGACTGTGTCTCCCCCAGCvacuolarproteinsorting28homolog(S.cerevisiae); tinA-52residueribosomalAAGGTGGTTCTTTCCTTGAAGGGCAGCCTCCTGCCCAGGCCCCGTGGCCCTGGAGCCTCAubiproteinfusionproduct TTTGTAGACACCTCAAATTATATCACTGTTCTCTAGCGCCAATATTCCCAGGTAAATTGAmultipleEGF-likedomains9;MEGF9 CAGAGTGCACCTGACACTGCCATCACATCGTCAGTATCACTGCCTGTCTCTGCCACCAAAsimilartohypotheticalproteinMGC49416;unassigned CCAAATTAGGCTTAGACTGTGCAAAGGGCTTAGCTAAGTTATCGAGCTTAAAACCCGTCAfamilywithsequencesimilarity129,member CTCCTGTATTACCGCCGAGTGGACCTGCTGTAAACCCTGTGTGCGCTGTGTGTGCGCCCAubiquitinspecificpeptidase10;USP10 containing1;MBOAT1 Genename/symbol TTTCCTCTATATTCGTTCTTGGCTCCCTTGTATATTTTTCTCAGGAGGCGTCACGGTGGGinsulininducedgene1;INSIGI CACCAAGCTGTCTGGCGCATGTGCCCTGGGCATCTCCACCCTCAGTCTGGAGTTCTCGGGhypotheticalproteinLOC388931;unassigned GCTGAGAAATTCAGCTTTGTTTTAGTTGAATCATCATATTGGAAAGCAGACATTGAAAGTmembraneboundO-acyltransferasedomain AAACATGAACAGCACCAAGCTCTCAGCTGACACCTACGAAGATCTGAAGGCCAAGCTTCCC-Mafinducingprotein;unassigned 1;UBA52 A;FAM129A CTTCCTGCTCTCCATCATGGCGCAGGATCAAGGTGAAAAGGAGAACCCCATGCGGGAACTribosomalproteinL11;RPL11 GCGGTTTCTTTCTTTCCGCGCCGATAGCGCTCACGCAAGCATGGTTAACGTCCCTAAAACribosomalproteinL36a;RPL36A TTTTACTATTGAACTGTATTCTAGTGGCTGTTCATGCTCCAAGACTTTAGTTACCGAGACMAXbindingprotein;MNT ACCCCATGCTCCCCAAGAACGCGGCTCTGCGCTGGAAGGCTGTGGCCTCTTGCTCCTCCTkeratin3;KRT3 VPS28 TABLE5-continued Sequencesidentified TTTGTGATGTCATTTGCCTGTGTCATGGCCTGCCTTCCCTAGATATTGTCCTAATGTGAGunassigned ATGGAGCTGTGCAAGTTGGAAGCCGCGGAGGCTCTCGGAACATGACCTACCTGCCGGCGGLOC494150 TCTGTGCCTTGGCAACAAAGCGCCACTACTCCATAACCCCATGAAACCTGCCCTGCCCCCunas CGCTCCATCTCAGCTTCCCCATGTGGTGCTGTGCTCTGTGGTGGCCAAGACTGCCATGTTunassigned

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 215650 216444 216522 216646 217271 217706 218186 219723 220179 220354 220708 222023 222435 223755 225147 230672 232022 No./ABI SEQIDProbe No.ID 1203226296 Probe 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1204 1205 US 2012 /0295815 A1 Nov . 22 , 2012 80

CCCGAGTCCCCTACCACTTCCGGGCCCCCAGCCGCATCTTCTGGCGGACCGTGCGAGGTAsimilartoribosomalproteinL13a;unassigned GCAGTAAGAAAACTGTAAAATTCGAGCCATATAAATAAAACCTGTACTGTTCTAGTTGTTSUB1homolog(S.cerevisiae); Genename/symbol BC052596;unassigned AGCCTGGACCCCGACACGCTGCCTGCTGTTGCCACACTCCTCATGGATGTCATGTCCTACoppositestrandtranscriptionunitto STAG3;unassigned GGTTGGGAGGCCATGGAACCAGGATTAGACCCACATCCGGCCACCAAGACCTCTGGCTCCRIBOSOMALPROTEINL5-RELATED TGGGCTGGATCCTCTGGTACACCGGCAACATCGAGATCTCGCGCCAGGAGCTGGAGCGCGhypotheticalgenesupportedby CCCCACCTGACCTGGCCTCGGCCATCAGCAACTGGGTTCAGTTTGAAGATGACACACCCTstonin2;STON2 ACTCCTAAGACATACTTGTGATATTTCAATGATGCAATAAAAGACCTATTGATTTGGACC60SRIBOSOMALPROTEINL9 CTCGCTCTCTGGGCAACAACAGATATCAGAAAACACTTGCCATTTATTTATAACCTAAGCGLYCOGENIN-RELATED CTTCAATATTGGTGATGCCCTGGACAGCAGCAGCTCCATGTAAACCATCCAAAAGACCACKERATIN,TYPEICYTOSKELETAL GATGGGTAGTTAGATTTCCCAAAATTTCTTAATCTGATTGGTGGCCTAGCTGCGGCTTGCS100CALCIUM-BINDINGPROTEINA11 RIBONUCLEOPROTEIN GGTGAGGAAGGCAAGAAAAGCTGGCAACTTCTATGTACCTGCAGAACACAGATCGGTATT60SRIBOSOMALPROTEINL7 TGATGGTACCTTAGATCACCCCTACAGCCATGCTCTGGTGGCTGGAATTGACCGCTGTCCPROTEINL27E60SRIBOSOMAL AGCGTACAACAGTGATACATGTAACCCCAAATGTGATGTGAGAGGACGATTACTTTGTAAgbdef:HypotheticalproteinFLJ20958 TABLE5-continued Sequencesidentified GTTTCAATACAGTGTCCCAGGCAGTCACTACCTATAGATTAGAGCTGATGTGCTGGCCTGunassigned TTTCTTGTATTTCTCTCACGTTAACAAAATTGGTTCAGCATCTACCATGGGCTACATGCTUNCHARACTERIZED CCCCCGGAGCCATGGCCAGCCCTTCCCGCAGCTCCGAAGCCACTGGCAAGCCCCGAGGCAunassigned AAATACACAGAGGTCCTCAAGACCCAGGGACTCCTGAGCCCAATAAAGACTATTAATTCCunassigned GATTTTGGACCCAAGAAGGGAGAAAACTTTGGAGGCAGAAGCTCTGGCCCCTATGGTGGTHETEROGENEOUSNUCLEAR AAAGAAAATTCATGTGAAAGTTCTCAGAGTCGTCCTTGTCTACTCCACTACCAAATGTTGP40 AGCCCCTGCCACTGCCTTCACCAGGCCCAGCTCACACACGGCTTGGCACCGTGCACAGAGunassigned ATTAATCTTTCTTAATTGGTTTGCCTGTTCTGCTTCTGTAAAAATTGCTTCAGCTAAACTunassi

occur.)oligonucleotideSequences

(Freq. of 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 90 232526 232819 233835 234327 234978 234984 234990 235306 236048 236152 236473 236503 236579 236585 236724 236885 243149 312026 351916 697257 697295 No./ABI SEOIDProbe No.ID Probe 1206 1207 1208 1209 1210 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 1224 1225 1226 US 2012 /0295815 A1 Nov . 22 , 2012

N,aminopeptidaseMmicrosomal AACAAGGACACCAAGGTACCCAATGCCTGTTTATTCACCATGAACAAAGAAGACCACACADNAdirectedRNApolymeraseIIpolypeptideJ-related AAGAAAAGCCATCTATGTACTGAACCCGGGACTAGAAGGAAAATAAATGATCTATATGTTproteasome(prosome,macropain)activatorsubunit2 AAACAACTTGACCAAAAATTTGTCACAGAATTTTGAGACCCATTAAAAAAGTTAAATGAGapolipoproteinLdomaincontaining1;APOLD1 AAAGTTTATCTATAACCTGGAAGACCATGAGTGGTGTGAAAACATGGAGTCCGTTTTATAsolutecarrierorganicaniontransporterfamily, AAATATATACGTCTATTCTTTATGCCTTGCCCTAGCCAGATGGAAGAAGATGAAGAAGGAKruppel-likefactor7(ubiquitous);KLF7 AACGCCACCCACTGCCAATACAACTTCCCACAGGTGGGCCGCACGGCTCTGCGGGTGCTGchemokine(C-Xmotif)receptor3;CXCR3 DPM2subunit;regulatory2, AAGAGGAATGTGTTGAATGTCGCGTTTGCTGTCCACTCGTCCTAGAAGTTTAGTGTTTTTtargetofmyb1-like2();TOM1L2 CD13,p150);ANPEP AAGAACAGGGTTGGGACCTTTTCTGCCCCTGCCCCTTAGCTACTGAGGCATAGGGAGAGGglucocorticoidmodulatoryelementbindingprotein Genename/symbol member3A1;SLCO3A1 AAATTGGAAGCTGTGCAGTATAAAACTCAAGTTGTTGCTGGAACAAATTACTACATTAAGcystatinA(stefin);CSTA AACAACTGGAGGGAGATCCCAGAAAACCTGATGGACCAGTACAGCGAGGTTAATGCCATCalanyl(membrane)aminopeptidase unassignedgene; (PA28beta);PSME2 AAGCAAATCCGGCCATGAAGACTGTCTACAAGTTCGCAAAAGATCATGCAAAAATGGGAADENN/MADDdomaincontaining1A;DENND1A AAGCTCATTCTTAGAACTTACACATCTAGAACAGCTTCCACTTTGGCAGTGAGGTCGTAGcalciumbindingprotein39;CAB39 CTCCTATGTTGGAAATTTGTTCATTAAAATTCTCCCAATAAAGCTTTACAGCCTTCTGCAGantigen6;GAGE6 TCCCAGAAGTGGTTGTTTCCCTTGCATGGGACGAAAGCTTGGCTCCAAAGCATCCAGGCTdefensin,alphal;DEFA1 2;GMEB2 AAGAGAGTGACCAAGAAGGCTCAGTGAAGGTCCCGCAGGGATGAGGCTGCCAGCCCCTTCdolichyl-phosphatemannosyltransferasepolypeptide TABLE5-continued Sequencesidentified TGGTGTCTAGCACATTCCTCTACCTTATTTTCTGTCATTGTACCTACTTCTACCTGAACAunassigned AAACTACAAAGAATACTGTGCTAAGGCTTGAGTGCGTTGAGCCCAACTGCAGATCCAAGALOC284230

occur.)oligonucleotideSequences (Freq. of 90 90 90 100 100 100 100 100 100 100 100 100 100 100 100 100 100 704151 712587 714879 100771 101113 101958 102040 102437 102558 102604 103589 104196 104280 104697 104772 105079 105463 No./ABI SEOIDProbe No.ID Probe 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 1241 1242 1243 US 2012 /0295815 A1 Nov . 22 , 2012

lipocalin2(oncogene24p3);LCN2 pyrophosphatephosphatase;unassigned AGAACTCAGGGTGGCCCTATGACTTGGAGGAGCAAGATCAGACCGCTCAAAGGTCCCCGTleucinezipper,putativetumorsuppressor2;LZTS2 AAGGAGCCCAGGAACTGAGGCGACTCGCCCCACTGCCATGTCCAAAAGCTTGAAAAAGAAmembraneassociatedguanylatekinase,wwand PDZdomaincontaining2;MAGI2 ACACATTCCAGCAAATGTATTTGCAATTATGTGGTTGATGCTTTGTGATATAAATGTACTfarupstreamelement(FUSE)bindingprotein ACATACAGCAGCTCTATTGAATAACATGCATCTGAATTTTAAGTTGCAAAGGTATCTGAAzincfinger,AN1-typedomain5;ZFAND5 AGACCATCACTGACGAGTTTGAGCAGGGCACCTACATCTACTTTGACTACGAGAAGTGGGCCR4-NOTtranscriptioncomplex,subunit3;CNOT3 AGAGATTCCTCTGCGAATCTGTTTTTAGCTATCAAGTGGCATCCACGCTTAAACAGGTGAchromosome10openreadingframe104;010orf104 Genename/symbol AAGCTGACCTTTCTGAGAAGTTGGTATGGTGTAACACTAAAGTAGGTGGTTCGTGTGTGTRas-relatedGTPbindingA;RRAGA AATGGCTTTGGCCACAGCCGTCTTGTGAAGGAAAACCTGATTGACTACTTCATCCCCTTCtorsinfamily3,memberA;TORJA ACACAGTGCGAGAGGGCATCTTGGATACAGCTCAGACCATCTGTGACGTGGCATCGCGGGhypotheticalproteinLOC23130;unassigned AGACCTCAAGTCTGCCTCTACTGTGTCTCACATCACCATGTAGAAGAATGGGCGTACAGTNEL-like2(chicken);NELL2 ACAATGCCAGCCCGCTGCTTTTTCTATCCTCCCAGTCACCTTTGCAGACAAAGACCAGGGphospholysinephosphohistidineinorganic FUBP1;1 ACCAAGAGACAGAAACAGAAAAACATTAAACACAGTGGGAATATCACTTTTGATGAGATCPROTEINL1260SRIBOSOMAL ACGTGCTTACTACTGCAGTGCATTTGTCATTAGTCTTCATGTTAATACAGTACATTTATTEH-domaincontaining3;EHD3 ACGTTGTCGCCAAGTCCCGGGACTTCTGGTACTTCGTATCTCAGTTAAAAAAGATGAAGA60SRIBOSOMALPROTEINL18A ACTATTGGATGTTAGTTTGGAGTCCTGTGTGCTTCTCTCTCTTATGGCTGTGTCCCTGGTUBIQUITIN1,2 ACTCTAATTGAGATTTTGGCATCAAGAACTAACAAAGAAATCAGAGACATTAACAGGGTCannexinAl;ANXA1 RIBOSOMALPROTEINL7AGAATTTTGCAGAGCTGAAGGTCAAGTGCCTGAGAAAGAAGTTTGCCCAAAAGATGCTTT60S TABLE5-continued Sequencesidentified AAGTGGAGGAGTAGCTCAAGAAGAAATGTTTCACTCTGCTCTGGTACTATGATCCCAATTunassigned ACAGGATGGGTGCCCGACCAGCCCACCGCCCGTGAGAGCTCCAGGA?TGAAGCCGCAGAGunassigned ACCTTCCTCCCTCACTGGACTTCAGTGTGGGACCTGCAGGTCTCAGGCCTTCTGGGAAGTunassigned

occur.)OligonucleotideSequences (Freq. of 100 100 AATGCAATTCTCAGAGAAGACAAAGACCCGCAAAAGATGTATGCCACCATCTATGAGCTG100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 105497100 105744 106478 107457 107655 108775 108944 108974 109712 110009 110634 112366 113059 113121 113409 113729 115418 116147 116214 116682100 No./ABI SEQIDProbe No.ID 1261115935 Probe 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1262 1263 1264 US 2012 /0295815 A1 Nov . 22 , 2012

ATCCTGCTGCTATTCCGCCTTCATTAACAGACTACTCAGTACCATTCCACCATACGCCAAproteininhibitorofactivatedSTAT,2;PIAS2 ATGCTGCGGGCCATTAGAGATTTCTTCTGGAAAACTGGAAACAAGATAGGGTTTAAACCA2-deoxyribose5phosphatealdolasehomolog(c.elegans); AGCAACACTTTGTGATCTCATGGCTTTGATTGATTTGGGCTGTTCAAAATGTTTATTTGAchromosome9openreadingframe156;C9orf156 AGCGATTCCTTGCAATAATGTGGAAGTCCTCATGAGTGGCAATGTCAGGTGTTATAATATleucine-richrepeatkinase2;LRRK2 AGGATCTCACATTTCACCCCAGGCTCAACTGAGGATGTGGCTTATTAAACACGGAAGTGCT-cellleukemiatranslocationalteredgene;TCTA AGTACGTGCCCTATGGCCCCGTGATGGAGGTGCTGCCCTACTTGTCCCGCCGTGCCCTGGprolinedehydrogenase(oxidase)1;PRODH ATATCAAGGGACAGCTCACAGACATACTGCAGAAGTCCTGTTGGCTGAGATAGGACGGCCanaphasepromotingcomplexsubunit1;ANAPC1 ATCAGTAAGCAGGAATATGATGAGGCTGGTCCTCCTATCGTTCACAGAAAATGTTTCTGAsimilartoRIKENCDNA4732495G21gene;unassigned ATCTCCAACAATCAAAGCTAGACGTAGCAGGAGTAGAAGCTATTCTCGCAGAATTAAAATchromosome6openreadingframe111;coorf111 Genename/symbol AGATACAAAACTTATTTCCATGTTTCTGAATCTTCTTTGTTTCAAATGGTGCTGCATGTTN-myc(andSTAT)interactor;NMI AGATTCAATCCTGTAATGTGTGAAAACATACCTCTAGATGAAAGTCGAAATGAAAAGCTGpatatin-likephospholipasedomaincontaining AGTCACCATCGCACAGGGTGGCGTCCTGCCCAACATCCAGGCCGTGCTGCTGCCAAAGAAhistonecluster1,H2aj;HIST1H2AJ ATACGAGTGGAATGAGGTGAAGAACGTCAAATCCATCGTGCCCATGATTCACGTGTCATGJumonjidomaincontaining3;JMJD3 CAAATAGTTCATCAAAATGAATCTTTGCTCTTTGGA?TGAATTCTTACCATACTGCCATTphosphorylasekinase,beta;PHKB RIBOSOMALPROTEINL21AGAGGCCACAGAGAAAGAAAGGTACCTGGGTTCAACTAAGCTCCAGGCTGCTCCACCCAA60S AGATCACCGCCGCGAGTAAAAAGGCTCCAGCCCAGAAGGTTCCTGCCCAGAAAGCCACAGribosomalproteinL14;RPL14 8;PNPLAN AGGAAGCAGAATGGCTATGATGGGCAAACTAAGCCGATTTTCCAGAAAAAGGCTAAAACT60SRIBOSOMALPROTEINL44 AGTACTTCTGCAGATCTAAGAGATTGCTGGCTATTAAAAGATGCAAGCATTTTGAACTGG60SRIBOSOMALPROTEINL44 ATCCTTACAGACCATTTGAGGGCTTCCTCATCGACTTAAAGACCCGCTATCCCATATTGGcyclinH;CCNH DERA TABLE5-continued Sequencesidentified AGCCTGGTGCCGGCTGACAGCTCACTGGAACTTTTCATCTGCTTGGCCAGGTGATGCCAAunassigned ATAGTGGAGAGTAGGAAACTGTACTTTATCTCGGCATCCTCTTGAATGATAGTGCAAGTTtitin;TTN

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 116953100 117219 117300 117625 117790 119015 119132 120117 120662 122309 122327 122554 124424 124706 125410 125981 126008 126331 127723 130995 No./ABI SEOIDProbe No.ID Probe 1265 1266 1267 1268 1269 1270 1271 1272 1273 1274 1275 1276 1277 1278 1279124803 1280 1281 1282 1283 1284 1285 US 2012 /0295815 A1 Nov . 22 , 2012 84

CAGTATCAGGGATCTACTGTCTTTGTTCAAAGGTCAAATAAAAACCTAGTCTCCTTTTAThippocampusabundanttranscript-like1;HIATL1 100CAAGGATCTCTCTCACTAAAGGCATACAGACTGACTCCTAAACTGATGGAAGTTTGTAAAeukaryotictranslationinitiationfactor3,subunit CAAGTTCGTGTACAGCCAAAGAGAGCTATTTGAGCCTTGGAATAATCTGCCTAAATATTAapolipoproteinBmRNAeditingenzyme,catalytic APOBEC3Glike3G;polypeptide- CACGGCAGCTCTCCGCCAATTTCTCTCAGATTTCCACAGAGACTGTTTGAATGTTTTCAAtransforminggrowthfactor,beta-induced CAGAACCTGAGCGACCTCTATCGTTGGCTTCAGGCCCAAAAAGACAAGATGTTTTCCCAGleucine-richalpha2glycoprotein1;LRG1 CATAGAAGCCATGTCCAAGCTAAAGCCTTACTTTCTTACTGATGGAACGGGAACAGTCACacetylacetyltransferase-CoenzymeA2(acetoacetyl CoenzymeAthiolase);ACAT2 CATGCTGGCCTACTTCATCACCTGGGTCTCCTTTGTGCCCCTCCTGGCCAATGTGCAGGTtastereceptor,type1member3;TAS1R3 Genename/symbol EIF3S3kDa;40gamma, CAGCCATAGTCAATCCCACGGTGTTCTTCAACATTGCCATCAATGGTGAGCCCTTGGGCTsimilartopeptidylprolylisomeraseAisoform CAGGTGCAACAGGTTCAGGTGTTTGCTGACGTCCAGTGTACAGTGAATCTGGTAGGCGGGnuclearreceptorcoactivator1;NCOA1 68kDa;TGFBI CACAAATTTTATCAAAAATCAAAGCTATTCCTCAGCTCCAGGGCTAGCTGCGATCTGTGT60SRIBOSOMALPROTEINL6 CAGATAACCCTTTGATTGCTTGATCTCTCGGTAAATATGGCATCATCTGCACGGAGGATC60SRIBOSOMALPROTEINL7 CAGATGAACCTGTAGCAGAGTGGAACTTGTACTAACTTATGATAGAATGTATCAGAATAATRANSLOCASEOFOUTERMEMBRANESUBUNIT TOM7 CAGCAGGTCCTGAGTGAAGCCGTGGGCCCTCCAAATGCTCGTTTTATAGCAACCTCTCTCMAX-likeproteinX;MLX 1;unassigned CAGCGCAAGATTGATCAGAAAGCTGTGGACTCACAAATTTTACCAAAAATCAAAGCTATTribosomalproteinL6;RPL6 CAGCTCTCCTGAAAGCTTCTACCAGAAAAGCACCTGCTGCTAAAGTOCCAGCAAAAAAGAPROTEINL1460SRIBOSOMAL CATTACTCGACAGATGTGGCACCGATCTTTAGCCAGAGAACTCTCTGGAACCATCAAAGA60SRIBOSOMALPROTEINL12 TABLE5-continued Sequencesidentified CAGTTGAGTGATAGAGTTAACCCCTTATCTGTAAGTTTTGAATTTACATTGTTTAATCCCunassigned

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 132033 132276 132679 133906 134602 135140 135209 135492 135636 135833 135977 136743 136898 137330 137563 138471 138834 No./ABI SEQIDProbe No.ID Probe 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 1296 1297 1298 1299 1300 1301 1302 US 2012 /0295815 A1 Nov . 22 , 2012 58

CCATCTCTGTCTAGCAAGCAGCCTCCTAAGATAGCTGTTCTCCCTATCATGACGGTGTAGtriggeringreceptorexpressedonmyeloidcells-like glutamine/Q-richassociatedprotein;PCQAP CCTTACACGTACCTCTCATCAGTGTCCTCTTGCTCAAAAATCTGTTTGATCCCTGTTACCsolutecarrierfamily2(facilitatedglucosetransporter), CATTAGGAAGTGACTTAACAACATTAGGCCTCAATCTGAACTCTCCTGAAAATCTCTACCCCR4-NOTtranscriptioncomplex,subunit2;CNOT2 CCATGACCACCTGCAGCCGCCAGTTCACCTCCTCCAGCTCCATGAAGGGCTCCTGCGGCAkeratin14(epidermolysisbullosasimplex,Dowling spleentyrosinekinase;SYK CCCCTGCATTTGTCCTGGGAAACACGGTATTTAAGAGAGAACTATATTGGTATTAAAGCTmitogen-activatedproteinkinase CATTCGTGTTCTGTGTATACCAAATGATTCTGTTATCTAAAGAAGCTTTTTGCTGGGAAAbonemarrowstromalcellantigen1;BST1 CCAAACCCTTGTCATTTCCCCCAGTGAGCTCTGATTTCTAGACTGCTTTGAAAATGCTGTtelomericrepeatbindingfactor2,interacting CCAGAGCACAGAAGACAAATGTATATTCAAGATAGACTGGACTCTGTCACCAGGAGAGCAadhesionmolecule,interactswithCXADRantigen Meara,Koebner);KRT14 CCCTGCCGCCGCCGAGTCGCGCGGAGGCGGAGGCTTGGGTGCGTTCAAGATTCAGCTTCAmitochondrialribosomalproteinL50;MRPL50 CCTGGCCAACATCCGCTCACCTGTCTTCAACCATTCCCTGTACCGCACATTCGTTCCAGCPC2(positivecofactor2,multiproteincomplex) Genename/symbol TERF2IPprotein; CCCACTCCGTCTACAGCCTCCTGTCTGTGTTTAGCCAGCGCTTTTACTGCGGTTCCTCCTGprotein-coupledreceptor45;GPR45 CCCATCCCACTCCCTGTTTCGGGCCTCGTCTGCTGGGAAAGTCACTTTTCCAGTATGTCTtripartitemotif-containing31;TRIM31 CCCTACGCGCCTTGTCTCCTACTCCTGACTCCTACCTGCCCTGGAACATCCTTTGCAGGGchromograninA(parathyroidsecretoryprotein CCGCACTTCAGAGTTGAGTCATTTTCTGAGGATGAATGGAATTTACTGTATGTTGCAGTAF-boxprotein,helicase18;FBX018 member1;SLC2A1 1;AMICA1 CCAGTCTGTGGGCTGCAATGTTGATGGCCGCCACCCTCATGACATCATAGATGACATCAA60SRIBOSOMALPROTEINL12 2;TREML2 2;MAP4K2 1);CHGA TABLE5-continued Sequencesidentified CCCAAGCCCTCCCCTCACTGGAATTCTTCTTGCTCTGTGAGCTAGCCTCATCTTCAGTTGunassigned CCTCAGCTTTTGCACACCTCCAATATATTGTCCACTGAAGTCAGAATAATSTAAAAATAAunassigned

occur.)OligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 CCCCTCAATAAGTATTTGCAGCAGAACAGACATGTCAAGGATAAGAACATCATAGAACTG100 100 100 100 100 100 100 100 138851 138962 139305 140620 141286 141595 141639 142046 142242 142562 143113 143169 143546 143873 144379 145493 146990 No./ABI SEOIDProbe No.ID Probe 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 1319146599 1320 US 2012 /0295815 A1 Nov . 22 , 2012 98

CTTTAGTGAGTACCCCTTTAGTGCTATATTTGTGCCATTCATTATCTGGTTCATATTTCTsolutecarrierfamily35(CMP-sialicacidtransporter), CTATTTTCAACATAACTGAAGGCATATGCTGGCCCATAAACACCCTGTAGGTTCTTGATAtransporter1,ATP-bindingcassettesubfamilyB CTCAAGGCAGCTAAGCGAGAGCTTCAAGAGCAAAGAGTTTGTGTCTAGTGATGAGAGCTCstructurespecificrecognitionprotein1;SSRP1 CTCCATCACCTTTGGGCTTGTTTTCTACTTTGCCACAGATTATCTTGTACAGCCTTTTATpresenilin1(Alzheimerdisease3);PSEN1 CTCTGAGATGAGACTGTACAAGAATATTCCACAGATGTCCTTTGATGATACAGAAAGGGAchromosome1openreadingframe128;clorf128 CTTCTACGGTTTCTTTGTCTGCGGAATCAGGGAAGAGTGAAAAGGGTCAGCCACAGAATTNADHdehydrogenase(ubiquinone)flavoprotein3, CGGGACATTGGCGTTCCCATGACCAGTGTGCGGCTGCCCTGCTATTTTGAGAACCTCCTCNmrA-likefamilydomaincontaining1;NMRAL1 CASP5peptidase; CTACAGCGGCTTCGAGGTGCTCTTTGCCTGCACTGGTATCGCCTTGGGCTATGGCGTGTGunc-93homologB1(C.elegans);UNC93B1 CTGTCGGAAGACCGTCAACGGCCACCTGGACTCCTATGAGAAAGTCACCCAGCTGCCGGGsuppressorofcytokinesignaling3;SOCS3 CTTTGTAACCATGTATTTACTCTGCCAGGTGCCTATATTCCAATAAAATGTTCATCCTTGfamilywithsequencesimilarity129,member Genename/symbol CCTTTTCAGGATTTAGGCCTGTAAGAAACTATGCCTGATTCTGTAAAATAAGTGTAAAGAexocystcomplexcomponent6;EXOC6 (MDR/TAP);TAP1 memberAl;SLC35A1 CGATATGACCTGCCAGCATCATACAAGTTTCACAAAAAGAAATCAGTCTGATCATCTAAAmethyltransferaselike5;METTL5 CTAAAGCCCAGATGCCCACCATAGAACGAGCAACCTTGACAAGAGATTTCTACCTCTTTCcaspase5,apoptosis-relatedcysteine 10kDa;NDUFV3 (H);HNRPH1 CTGTCGGTCTCAGTACGTTCACTTTATAGCTGCTGGCAATATCGAAGGTTCCTTTTTTGTralAbindingprotein1;RALBP1 CTATGGGCGTGAACGGAATGGGAGGGTTGTCTAGCATGTCCAGTATGAGTGGTGGATGGGheterogeneousnuclearribonucleoproteinH1 A;FAM129A 147295100CCTTGAATGAGCTATATTCAGGGTATCCGGTATTTTGTAATAGGGAATAGGAAACCTTGTsulfatasemodifyingfactor1;SUMF1 CGCCGAAGGCGACCGGTCGTCCACACCGAGCGACATCAACTCCCCTCGACACCGGACACAkazrin;unassigned protein;TARDBPCTAATGTCTGTTAGCTACCCATAAGAATGCTGTTTGCTGCAGTTCTGTGTCCTGTGCTTGTARDNAbinding TABLE5-continued Sequencesidentified CTGCGCTCCGCCGTCGGCTCGGGCTGAAAAAGTTTCTCCATGGTTCCTTTGTGTCGCCCGunassigned ??????TACTAAAATGCAGTAGAGGTACTCTICTGTccc??ccGTTTATAGTTCTCTGAGunassigned

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 147612 148241 148692 149705 150701 150896 151002 151695 151778 151867 152539 153516 155096 155386 156493 156497 157702 158453 158787 No./ABI SEQIDProbe No.ID Probe 1321 1322 1323 1324 1325 1326 1327 1328 1329 1330 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 US 2012 /0295815 A1 Nov . 22 , 2012 87

Gpolypeptideirected) GAAGTGTGTGGCTGGGCGGATTCAGCGAAGTCTCATGGGAAGCAGGACCTAGAGCCGGGCwingless-typeMMTVintegrationsitefamily,member GAATGAAACCTATAGCCTTTGTGCTGTTCTGCCTTGCCTGTGAGCTATGTCACTCCCCTChexosaminidaseA(alphapolypeptide);HEXA GACCAGCGGCCCACCAAGAGCTGGCTCAAGAAGTTTCTGGGCTTCGTTGTGGACCCCAACperoxisomalproliferator-activatedreceptorA interactingcomplex285;unassigned GAGGACGTGAGCCAGTTTGATACCCGCTTCACACGGCAGACGCCGGTGGACAGTCCTGATribosomalprotein56kinase,70kDapolypeptide GAGTGTGCTCCCCCGTCATGCAACATCTGGACACAACTAACAGAGCATGGTGAATACATGtransmembraneandcoiled-coildomains4;TMC04 GATCCTAGGTTCTTCCTGACTGCTTTCTCCAACTGTTCACAGCAAATGCTTGGATTTTATtransmembrane9superfamilymember3;TMOSF3 GATTGACCTGGCCAAGCTGAAGAAGTTTATTGCCTACTGCCGAGTGAAGTGTGGCCCCCGMCM5minichromosomemaintenancedeficient5,cell divisioncycle46(S.cerevisiae);MCM5 GATTGCTCCTGTGTAAAGATGCCTTGTCGTGCAGAAACAAATGGCTGTCCAGTTTATTAAsplicingfactor,arginine/serine-rich2;SFRS2 Genename/symbol CTTTTAGTGACCACGGGCTACATCATATGCTTTGTTCCTTACCACATTGTCCGAATCCCGGprotein-coupledreceptor171;GPR171 GAACGGATTACAATTCTGCTCCCCAAGAGGCCCCCTAAGACCACAGAAGATAAGGAGGAApolymerase(RNA)IIIDNAdirected (32KD)-like;POLR3GL GCAAGTCCCAACTTTGAATAAAACAGATGATGTCCTGTGACTGCCCCACAGAGATAAGGGABIgenefamily,member3;ABI3 GCACTGGAATAGGAAATGTCCCCCATCTCCCTTCCTGCACCCTGCTGTGCTCCCTCCAAATBC1domainfamily,member10B;TBC1D10B GAGCAACCTGCGAGACTCACAAGATGGGAAGCTGACAGAGATACCTACAGACAGAGTGCTribosomalprotein$10;RPS10 2;RPS6KB2 GAAGGCTCTCCATCGAAGGCAACATTGCTGTGGGAAAGTCCACGTTTGTGAAGTTACTCAdeoxyguanosinekinase;DGUOK 3;WNT3 GACCTTAATTCTCTTTCCCATCTTGCAAGATGGCGGGTGAAAAAGTTGAGAAGCCAGATAribosomalproteinL6;RPL6 GAGATTGCTGGCTATTAAAAGATGCAAGCATTTTGAACTGGGAGGAGATAAGAAGAGAAA60SRIBOSOMALPROTEINL44 GAGCCGCTCATAGACCCCGCCTGCCGTCCGGTCAATAAAATCCGCCTGACTCCTGCGCCCneuropeptideW;NPW GAGGGCCTGATCTGCATCTGCAGCATGAGGTTCTGCCCGTTTGCTGAGAGGACGCATCTGGLUTATHIONE-STRANSFERASEOMEGA GCACCAGTGACATTTAAAGGCTTCCGCGAGTGAATGAGTGCTTCTTAATCCTAAAAACACMAD2L1bindingprotein;MAD2L1BP TABLE5-continued Sequencesidentified 100GACTGTGGACTTCATGATTGTTGTACTTCTGGGTCAAAACTCAAATGAGGTGAATTTTGCunassigned occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 158846 160844 161046 161271 162222 162617 163152 164007 164041 164302 164721 165071 165502 166068 166975 167003 167575 167868 168086 No./ABI SEOIDProbe No.ID Probe 1341 1342160035 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 US 2012 /0295815 A1 Nov . 22 , 2012 88

GCCTCCCTGTTTGAAGCCTGCCCTTGTCTGAGATGCTGGTAATGGCCATGGTACCCCCTTguaninenucleotidebindingprotein(Gprotein),alpha inhibitingactivitypolypeptide2;GNAI GCCACTGCCTCCCCCGAATGCATTTGGAACCAAAGTCTAAACTGAGCTCGCAGCCCCCGCnuclearreceptorco-repressor2;NCOR2 GCCTCAAGAGGTGGTGGAAGAGTTGAAGAAGTACCTGTCGTAGGGAGATTTGGGTAGAAGchromosome11openreadingframe31;Cilorf31 GCGAACTGGGTTGCTTCCCTGAGGGCCCCCGCTGGCCAAGGCCTGTGGACGACGCTTGCGADP-ribosylationlikefactor6interactingprotein GGACGTGATAGCTCTGCCTATTGCAGGACAATGATGGCTATTCTAAACGCTAAGGAAAAAubiquitin-conjugatingenzymeE2Q(putative) GGCCACCAGCTGTTTCCCACGCCCCATGACTCCCCGAGACCGACATGAAGGGCGCAAACAnuclearmitoticapparatusprotein1;NUMA1 phosphatase;unassigned GGCTCCAAGGAGACAGCAACTCAGCCCTTGCCTCTGTATGACACACCCTATGAGCCAGAGSrchomology2domaincontainingF;SHF GGGACAAAATGAGAAGTCATCACTCTTTTTGGATCATTTAGATCTCTTGCATCCTTTGTTsimilartoHESBlikedomaincontaining2;unassigned Genename/symbol GCTTATAAGTTAAAGGGCATCACAGTGAGGGTGTAGTAGATAAATTCAAGGAAATAAGAGORM1-like1(S.cerevisiae);ORMDL1 GGACTATGCGGAGGCCCTGATCAACCCCATTAAGCACGTCAGCCTGATGGACCAGAGGGCphospholipaseC,beta3(phosphatidylinositol specific);PLCB3 GGCTCATTTGCTCTCTCCACTACTCATCTCTGGAATTAGCCGCTTAAATACAGGTTTTTGskeletalmuscleandkidneyenrichedinositol 100GCAGCCCTGGTTCAGGCCCGGAGGAGGGTTTGCGGGTAGTTGCACGGACAATTCGGCGGGdeath-associatedproteinkinase3;DAPK3 GCCATCCTACGCCGTAGCCGTCCAGAGACTGGCAGGCCTCGGCCTAAAGGTCTGGAGGGT40SRIBOSOMALPROTEINS10 GCCATGCTCTTCAGGAGGAGACTCCAAGGGCAAAGGAGGGTGTCTTGGCTGTGCTTGAAGphosphomevalonatekinase;PMVK GCCTGCCCACTGCAACGGAGCCGCCAGCACCTCCTCCCCTCCAGATCCGGGCCCCAGGCTataxin7-like2;ATXN7L2 4;ARL6IP4 GGAAGAAGGAGAGGAATACTAATTATCCATTCCTTTTGGCCCTGCAGCATGTCATGCTCCalphatubulin;unassigned GGAAGCTTTGTGAAGCTCAACAAGGCTTCCACTAACATGCTGAGGATTGTAGAACCATATPROTEINL760SRIBOSOMAL 1;UBE221 GGCCAGAAGGCAGCGCCTGCTCCAAAAGTTCAGAGGACTCAAAAACTCCAGCTCCTAAAAPROTEINL1460SRIBOSOMAL TABLE5-continued Sequencesidentified GCCCGCCCGAGCTGCTCGACGTGATGAAGCCCCAGGAGTCGGGAAGCAGTGCCAATGAACELONGINB GGGAAGAAGGGACAACAGCGGACTGTCTAAAGGATGCCTGGATTCCTTGTTTCTCAGGACHISTONEH2A

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 168498 169781 170047 170102 170472 171075 171160 171339 171710 174250 175122 175282 175938 175969 178191 178227 179141 179146 179752 179857 No./ABI SEQIDProbe No.ID Probe 1361 1362 1363 1364 1365 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 1377 1378 1379 1380 US 2012 /0295815 A1 Nov . 22 , 2012 ?

GGTGACAGAAGACACAGATGAAGATGCTCCCCTTGTGCCAGATGATACCTCAGACTCTGGpleckstrinhomologydomaincontaining,familyG(with GTCATCTTGCTTACCTACGTGCTGGCCGCCACAGAACTTACCTGCCTCTTCATGCAGTTCsolutecarrierfamily22(organiccationtransporter), GTTAAATACCACATTATTTGAAAGCTGGGAGATCGTTGGACCTTACCCTTCCTGGTGGGTLAGIhomolog,ceramidesynthase6(S.cerevisiae); RhoGefdomain)member6;PLEKHG6 GGTGATCTGCTTTTATCTAAATGCAAATAAGGATGTGTTCTCTGAGACCCATGATCAGGGsignaltransducerandactivatoroftranscription3 STAT3factorresponse);acutephase-( GGTGCTGGTGGCCTTTCCCCGGTGGATTGGTCTCTGGCCCAGCCCAGTCTCTTCTCAGGGADP-ribosylationlikefactor6interactingprotein GTGATCCCTCGGGATGACCCCCTCGTGCTCTATGTCTATGCTGCCCCTCAGGACATGAGGFYVE,RhoGEFandPHdomaincontaining2;FGD2 GTGGCCCTGGGATACCGGAAAGTGCAACAGGTGATCGAGAACCACATCCTCAAGCTCTTCregulatoryfactorX-associatedankyrincontaining GTTTACTTTGAAAAAGTGAAAAAGGCTTCCGGGCTGTCCTCTGCCCAGTGAGATGGAGGAinositol1,34-triphosphate5/6kinase;ITPK1 Genename/symbol GGGTGAGAAGAATAACCACAATTGTATGTGCCTGTTTTTTACTCTTAGCATTAGATGAAThistidineammonia-lyase;HAL member18;SLC22A18 RFXANKprotein; GTTATAGAAATCAGCATACTATTTTTTTAAATCTGGAGAGAAGATATTCTGGTGACTGAAralAbindingprotein1;RALBP1 GTTCAGGGCCAGGGCCTCCTTGGAATAAATGGTTATTGTTACTAGGTCCCCACCTTCCCTSH3KBP1bindingprotein1;SHKBP1 GGGCCCTCTCCATTGTGGCCGATGACTGAATCCCCGTCACTCTTGGAGGACTCCTGTGACbridgingintegrator3;BIN3 4;ARL6IP4 GTGGCAAGGCCTTTAAGCGCTCCTCTATCCTTACTACACATAAGAGAATTCATACTGGAGzincfingerprotein66;ZNF66 GGTCTTGTAATTACAGGAGCCATTTCTGTAGGTAACTGGACCAAGAATGAGAAAAATAATsortingnexin15;SNX15 GGTTCAGATCGATGGCCTTGTCCATGTTGTCCTTTCTGGCTTCCCTGATGGTGTCATGTTcyclinM3;CNNM3 GTACCACAAGAAGATCTTCCGGACTGCCATGCTGTTCCAGTTTGTGAACGTGCTGCTCCAexportin6;XP06 GTCTGAAACCCCTGGTAGCCCCGACTTCTTTTTAATTAAAATAAGGTAAGCCCTTCAATTCD99molecule; LASS6 TABLE5-continued Sequencesidentified GGTTGAAGTCTGTGGATGCAACTGTTAATGAAGATGGTTAAACTTGAAATAAACAATTTTunassigned GTTCTCCTTGGGTGACCCCCATGATGCCTGACCGCTCCTCGTGCCTCCTGGAACAGCCAGunassigned

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 180577 181086181086 181922 181993 182070 182204 182573 182667 183167 184157 184933 185593 186362 186433 187278 187446 187590 187824 188270 No./ABI SEOIDProbe No.ID Probe 1381 1382 1383 1384 1385 1386 1387 1388 1389 1390 1391 1392 1393 1394 1395 1396 1397 1398 1399 US 2012 /0295815 A1 Nov . 22 , 2012

acetylglucosaminyltransferaseMFNG; TCGAAGCAGTCAACCTCCCGGTCGACCATATCTCCTTGATCCTGGCTGTGGACTGGCTAGsolutecarrierfamily1(neutralaminoacidtransporter), TAGTAGTAGTACTGAGAAAAATCCCTTCAGCTCTAAGAACACTGAAAAATCCACCGATTTv-ralsimianleukemiaviraloncogenehomologB(rasproteinRALBbinding);related GTP TCAAAAGGCTATGTCTGCTCTTCAGTAATGACATGAAATCTTTGTTCATCTCCACTTTGTcomponentofoligomericgolgicomplex5;COG5 TCAGGGACGTCAATGTGTCTGCCTAGCCCTGTTGGCGGGCTGACCCTCGACCTCCCAGACarginylaminopeptidase(B)-like TCCCCATCCTGCATCTGGACGGTATTGTGGAGGACTCCTCCAACATCCTGGGCTTCTCCAglutamatereceptor,ionotropickainate5;GRIK5 TCCTAGCAGATGATACAGCAGTGGGCTACATACAATGAGAGCCCTGAGCCCTCAAGAACTcomplementcomponent8,betapolypeptide;C8B TUBULINALPHA-1CHAIN TCAAATCACTATCTGAAGGGTCACGGAGCGCAAAATAAAGTTTAAAACCCTGCTACCACAmitochondrialribosomalproteinL53;MRPL53 symbolnameGene/ TACCATGGGACCAGCTCTGGCCAGAGGGAACTAAGCAAATCCAATAGAGATGTTTCTGGGMFNGO-fucosylpeptide3betaN TAGAATTGAGAATCTGGAACTAATGTCACAGCATGGATGTAATGCCTGGAAAGTATACAADENN/MADDdomaincontaining2C;DENND2C TCCCACTGTCTCCCCCAGATATGTCCTTCCCAGCATCTTTGGCTGCACAGCATTTCCTTCcoiled-coildomaincontaining67;CCDC67 member5;SLC1A5 protein;unassigned TAGAAGATGAGGAAGATATAACACTTACAAGATGGACAGGGATGATAATTGGGCCTACAAUBIQUITIN-CONJUGATINGENZYME TATCATCTCAGTGAACCTACTGGTGGACTCCCAATTGACAAGATTGAGCAATAGAAAAAAralAbindingprotein1;RALBP1 TATGGTGGGCAAACCAAGCTGATTTTCCAGAAAAAGGCTAAAGCTACAAAGAAGATTGTC60SRIBOSOMALPROTEINL44 TCACTGAATACAGCACAGACAAGGACGAGCCTCCAAAGGACGTCTTTGATGAATTATTTAparvin,gamma;PARVG 1;RNPEPL1 TCGACAAATACCACCCAGGCTACTTTGGGAAAGTTGGTATGAAGCATTACCACTTAAAGAribosomalproteinL27a;RPL27A TCTAACAGACAAAATTGATGTACTTCTGCAACAGATTGAAGAATTAGGGTCTGAAGGAAAcisplatinresistance-associatedoverexpressed TABLE5-continued Sequencesidentified TACAAAGAAGACAGTGCTAAGGCTTGAGCGCGTTGAGCCCAACTGCATATCTAAGAGAATunassigned TCAGCCTGTCCAATAATGGAGCCCTGTCCTTCTACACAAGGCAGCCTAAACTACCCACCAunassigned TCCTGTAGTGCTGTCTCTGCTTTTTGCATCTTGCCCAGTATATTATGACACAAATAAAAAunassigned

occur.)oligonucleotideSequences (Freq. of 100 100 100TACCTGATGTATGCCAAGTTCCTTTGTTCAGTATTCCGTGGGTGAACGGGTGGAGGAAGG 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 189707 190174 190338 190885 190921 191530 192006 192464 192905 193007 193821 194223 194416 195881 196014 196577 197007 197251100 197267 197857 No./ABI SEQIDProbe No.ID Probe 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1414 1415 1416 1417 1418 1419 US 2012 /0295815 A1 Nov . 22 , 2012 91

TCTTTGGTGCTGCAGCGGCACACAACTGGCAAGGCTTAATCAAAAGACTGGAAAACTGCAacyl-CoenzymeAbindingdomaincontaining6;ACBD6 TGCCGTCAACATGCCTTTCATGGACTTCCTGACTGAGGATGGCTTCGAGAAGGGCCCAGAthiosulfatesulfurtransferase(rhodanese);TST TGGCATGGCTGCCTTGATGTAACATAATTCTCTGTCCCCAAGATTTAGAAAATTCCTCTTphosphorylasekinase,alpha2(liver);PHKA2 TGGTCTGATGCTCCTTCAAAAACATTCACTTTTTACAACGTCAAGGAATTAAGCATAAAAchromosomeXandYopenreadingframe3;CXYorf3 down-regulated8;NEDDS Genename/symbol TCTTGCTTGACCGTTTGGGACATCAATCTTCCACATGAAGTGCAAAATTTAGAAAAACACleucine-richrepeatkinase2;LRRK2 TGCAAGCCGCCGGCACCCGCCTGCTGCGACCCGTGCGCCTCCTGCCAGTGCCGCTTCTTCagoutisignalingprotein,nonagoutihomolog TGTATGTCTACTGGTGGGAGACTGTGAGGATCCCAGGATTCAGTATTCCTGGCCCAGAGGneuralprecursorcellexpressed,developmentally TGAGGGACATGGCAAGTTCCTGGCCACTGCCCAGAACCCTGCTGATGAGCCCACTCTAGGGOLGIAUTOANTIGEN,GOLGINSUBFAMILYA (mouse);ASIP TGCCCTTGAGTCCCCTGTGCCCTAGCAACCGGAGGAATGGAAAGGACCTCATCAGGGTGGhypotheticalproteinLoc146909;unassigned TGTCCCTGTTTTATAAACATAATCACAACAGTAATAAACCTCAAGTAGTGGCTAGTGTTTIonpeptidase2,peroxisomal;LONP2 TCTGCTGCTGCGGAAGGGACCCCTCGGAGGAGCATTCGCTGCTGGTGAATTGATTCGACCmucolipin1;MCOLN1 TGACAGGAACTTCCGCACCTCCTGAGGCCCTGGATGATTCTAATTGTTAGAAATTCTAATreplicationinitiator1;REPIN1 MEMBER2 TGGCTGGGCAACCTACGTCGCCTTTGGACCTCATGCTGGAAAATTCATTGTGATCATAGA60SRIBOSOMALPROTEINL14 TGGGAATCACGAATTTTCCTATTCCTGGAGAGCCTCATTTTCCACTTAACGCAATTATGCARP2/3COMPLEX21KDSUBUNIT TGGGTGCCACTGCCTGCTTGAAAGCACTTTCTGAACCTACAGAAGTTGGGTATTGTCTGAWDrepeatdomain59;WDR59 TABLE5-continued Sequencesidentified TGAAAAAACTACTAGGATCACGCGGCATGTATTGAGCATATAGGTTGCTGTAGATGAATGHBII-276HG TGAACTTTCAGCCAAGAAGGTAGTGTGAAAATATTACTGTGAGGTTTTAAAAGTACACAAunassigned TGACGCAGTATAAGAAGGGCAAGGATTCCTTGTATGCCCAGGGAAAGAGGCGCTATGATCLOC554234 TGATATCAGCCATCGTCAACCCCGCCGTGTTCTTCGACATCGCCGTGGATGGCGGGCCCTunassigned TGGACAAGAAGGAGCCTGAAGTCTTGCGGGACTCACTGGATAGATGTTATTCAACTCCTTUNCHARACTERIZED TGGGCTCTAGGAGACCCCAAATTTGACACCACAGAAAGCAAATAAAACACTTGAAATACGMGC10812

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 208243100 199121 199912100 200120 200176 200572 201125 201335 201923 202166 202737 203664 203712 205151 205981 206400 206536 206815 206925 207178 207943 No./ABI SEQIDProbe No.ID Probe 1420 1421 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 1432 1433 1434 1435 1436 1437 1438 1439 1440 US 2012 /0295815 A1 Nov . 22 , 2012

TTTCTCCATCCAATTCTTTGAATTTCCCAGTCTCCCCTATGTAAAACTTAGCAACTTGGGmajorhistocompatibilitycomplex,classIIDM TGTCCTACGAGCAGCTGGAGCAGCCGATGCAGCTGTACAGTGCGCGCCAGCGGCGGCGGCsimilarto40SribosomalproteinS15(RIG TGTCGGACTATGTAATTGTAACTATACCTCTGGTTCCCATTAAAAGTGACCATTTTAGTTfusion(involvedint12;16)malignant TTCGCTTTATTTTTGTAAGTATCACCTGCCACCATGTTTTGTAATTTGAGGTCTTGATTTmembrane-boundtranscriptionfactorpeptidase,site TTGAAAGTTATGTTTTAGGGTCCTCTGAAAAGCAAATTGTGTCAGAAGATAAAGAGCTTTchromosome21openreadingframe45;C21orf45 TTGTGACCATTAGCATTTGTCAACAAAGTCACCCACTTCCCACTATTGCTTGCACAAACCchemokine(C-motif)receptor1;CCR1 TTTCCGGAGCACTTGCAGAGGACTTGCTATTTGCCAGGTGCTTTATGTATCATTAAATTTisopentenyl-diphosphatedeltaisomerase1;IDI1 protein);unassigned liposarcoma);FUS TTCAACTCTGGCCCTCACAATCCAGTGGAGGAGACGAAACTCATCTGCCTCTGTCCCTCThypotheticalgenesupportedbyAK024248; TTTCAGGACCCTAGAGGAGAGCTTTATACAATTACCGATGTGAATTTCTCTAAAGTGTAThippocampusabundanttranscript1;HIAT1 Genename/symbol TTATCAGAATTCCGAGAAGGAGTGCGGAAGATTGCCCGAGAGCAAAAAGTCCCTGAGATTcysteinyl-URNAsynthetase;CARS AL137733;unassigned AY007155;unassigned beta;HLA-DMB TTCAAGGGATAGAAAGTCACAGTAAGGATGGCAATGCCAGTGGAACCAAGCTGCTTGAGGELONGATIONFACTOR1-ALPHA 1;MBTPS1 TTGGACCTAGTTGGTGATTATACTCTGTCTCCCATGGAGACCACGTCTTGCATCCTTCCThypotheticalgenesupportedby TTCAACACTGCCAATGATGATAACGTTACTCAGGTGCGGGCATTCTATGTGAACGTGCTGcatalase;CAT ??CAGTGTTGATC???????????????cTGTCAGGTGCACAAGATTAccc?cc??????14/032003 TTTAGCGTCTTTGAAGGAGACCAGACATGAGTGAATACCTAGGAGAGTGTCAGCATGTTTKIAA0317; TABLE5-continued Sequencesidentified TGTGCCAGAAACCCTTAAGAAAAAGCAAAGGAATTTCACAGAGCTGAAGATCAAGCTCCTunassigned TTCAGCCAAGTTCAGGGAGGTCTGAATACTGAGGCCTTCATAGCCACTGCACCCCAGGTAunassigned

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 208270 208343 208774 210798 211100 211120 211169 211400 211521 212389 213145 214080 214739 215225 215483 215616 215770 No./ABI SEQIDProbe No.ID Probe 1441 1442 1443 1444 1445 1446 1447 1448 1449 1450 1451 1452 1453 1454 1455 1456 1457 US 2012 /0295815 A1 Nov . 22 , 2012

AATTTGAGCCTCTGCTGAATTGGATGAAAGATAAAGCCCTTAAGGACAAGATTGAAAAGGheatshockprotein90kDabeta(Grp94),member dimethylallyltranstransferase, geranyltranstransferaseFDPS); CAGAGGGAGTGTGCGAATCTACCCTGACCAATGGGCTCAAGAATAAAGTATGATTTTTGAsulfotransferasefamily,cytosolic1Aphenol AAGAGCTCTGTGTCTTCTTAGTGGCTGTATCTTGGATTCTGTCTTGTGCCAGCTCCCTCTolfactoryreceptor,family1subfamilyJmember TTTTCCCAGGTACTGCCTTACAAAGCTGTGGCCAGGAAGTGGCCGGTATAAAGGATGCCCtumornecrosisfactor,alpha-inducedprotein pyrophosphatesynthetase, preferring,member3;SULT1A3 CCCTGTTCCTGCCCTGAAACAATTTCAATCACTGACAAATCATTATCATTCATTAATAATF-boxandleucinerichrepeatprotein14;FBXL14 Genename/symbol TTTCTGCTGTTTGATCTCTAAGGAACTCCTGTTGCTAAATATGAAGAGTATGGAACATTCtransmembraneprotein30A;TMEM3OA AGAAAGTGGCCCGGGTGAAGGCGCTATATGAGGAGCTGGATCTGCCAGCAGTGTTCTTGCfarnesyldiphosphatesynthase( AGAAGCTTCCTGAAATGGACATTGATTGATTCCAACACTTGTTTCTATTAAAACAGACTAheatshock70kDaprotein4;HSPA4 CCCCACCATTCTACAGAGTTGTACTCAAGACAGATACTGAAAAAATCTAATACCTTCCCTkelchdomaincontaining1;KLHDC1 TTTGGGAGAAATGGATCTGACTGCCCGGACAAGTTTTGCTTATTCCAGTCTGAAACCAAAlactotransferrin;LTF 2;TNFAIP2 1;HSP90B1 AGACGCCAGGAAGGTGAGATCTTCGACACAGAAAAAGAGAAATATGAGATTACGGAGCAGribosomalproteinL6;RPL6 AGCTGCCCGAGCGCCTGCTGCAGCCGCTCCACTTTCTCCACATAGGCCTGTTCTTGCTTTangiomotinlike2;AMOTL2 GCCCAGCCAGTTAAGCACAAAGGAAAACATTTCAATAAAGGATCATTTGACAACTGGTGAribosomalproteinL12;RPL12 GTGTTCCTCCTCCCTCTATTACTGTTTCACCAGAGCTGTCTTAGCTCAAATCTGTTGTGTscotin;unassigned 2;OR1J2 ACAAACTACAATCATCTTCCTGAGGCAGATTCCCACTAGGACTGCATTCAACTTAGAGCCPROLINE-RICHPROTEIN TABLE5-continued Sequencesidentified AACCAAGTAGCTGCAGCTCTCTACCAAGCCCTCCACCGGACCCTGTGGGCGGCGGCTGTGunassigned CGCTAAGCGCCTATGCCACTCGCCTGATGAATTTGGGAGGTCATAAAAGCCTCACATGGGunassigned GAATAACAGGCTGGTTGGAAATCTGGAACAGAGTATCCTGAGAATCTGCCCACCTTGAAGunassigned TGCTTCTGATTCCTACATCGTTTTCACCACTGAAATAGTTTTCTACTGAAATACAAAACANIPSNAPJA

occur.)oligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 215830 216357 216775 217447 217900 218546 218581 218636 218954 221030 221158 221657 222747 223546 225189 226803 228198 228421 No./ABI SEQIDProbe No.ID 1467220348 Probe 1458 1459 1460 1461 1462 1463 1464 1465 1466 1468 1469 1470 1471 1472 1473 1474 1475 1476 US 2012 /0295815 A1 Nov . 22 , 2012 94

CCTGCGGGTGACCCGGCCTCTGGTGCCAGAGCCTGCCATCCTTCCTGTTTGTGCTGCCAGchromosome9openreadingframe139;C9orf139 AGATGCAGGAATAAAGTAATCTTATATACAAGCTTTGATTAAAACTTGAAACAAAGAAAAzincfinger,MYND-typecontaining17;ZMYND17 symbolnameGene/ TAGCACACTCATGAACCTAATTCCCACATTTGATAGTTGTTACATTTTGCCATGTTTGTTLyrm7homolog(mouse);LYRM7 ATTAATACGCCAGTCATCATAAAAGATGGTCATTATAGTACCCCCATTGCTCCTGCTTGTAUTOPHAGYPROTEIN12 CAGCCACCTGTCAAGAGGAGGCGGAGCGTCATGCCTCTGGAAGACTGGATGAATATTCTCLOC253039|EHD2 TTGTTCGTTCTGCTCTGGAGACCCCTGGGTTGCGGCCCCTGGACCCCTCCACCCCTGCTGPLECKSTRINHOMOLOGYDOMAINCONTAINING PROTEIN AACTGGGAGGAGATAAGAAGAGAAAGGGCCAAGTGATCCAGTTCTAAGTGTCATCTTTTGPROTEINL4460SRIBOSOMAL AATAAAAGCTCGCCTTTTGTCTGTACATACTGGCCTCCGTGAATACATAGATCAGCCATT60SRIBOSOMALPROTEIN119 AGATAAGAAGAGAAAGGGCCAAATGATCCAGTTCCAAGTGCCATCTTTTATTATGAAGAC60SRIBOSOMALPROTEINL44 TTAAGAGATGCAAGCATTTTGAACTGGAAGGAGATAAGAGAAAGGGCCAAGTGATCCAGT60SRIBOSOMALPROTEINL44 TABLE5-continued Sequencesidentified GGCCACAGCTGCTCTCCAGGCCCACTATGCACACATCTTCCCCTCCAAGGTTTGTTCTGCCAPICUAPROTEIN CCCTGTTCCCACTCTACCACTGGAGGAAATGAGGACACAATCTGGTATCAACAGTTTGATunassigned CTCACCCTCCTCAGACTCTGCGGCGGAGAGCCGAGTGATGAATAAATGAGTAACCACATCunassigned GGGACCACCCTCATTTCCCAGCTTCCTCGAAGGGCAGACACTCCCCACAGCTCTGCTGCCunassigned GTTTCTTGGCTACACAGATGGGTCTGTCAGGGTTGAAGCCACATGGGTGCCTGCTCATGTunassigned100 TCATTGGGTTTAGGAAGGATTTCTCTAACACTGAGTAACATGAGGATTTAGCAGTAGTGTunassigned TTTAGATTTATCAGGCTTCTTCACCTCGCACTGTCCCCATCCTGGCCGCAGGCCCCCTCGunassigned TTTGTTCACACAGTc????CAGCTcccGCAccc???GcGcc?ccTGC???cGGATCATc?unassigned ATGGAGAGGAGAGATCGTGCTGTGTGTCATGTCTGTTGTTCAAGTAAATAAAAGTTGCCCLOC284454 CCTCCTCTCCCTCCCACTGCACACTCCCACTTCCTCAGCGACCGGGCCCTTCTCCACCTCunassigned GAAGAACCGAGTGTGTCCACCGATGTGGCAGCTGCAGCGGGCTTGGCTTTGTGAGGAACCunassigned TTCACCCCAGCAAGATTCTTGAATGGAAAGCCAAATCTCACCAAGTAGGAAAGGAAACGGunassigned occur.)OligonucleotideSequences (Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 229592 229944 230429 230540 230838 232377 232820 232981 233218 234288 234297 234359 234621 234758 235017 235219 235396 235909 236102 236177 236952 No./ABI SEQIDProbe No.ID Probe 1477 1478 1479 1480 1481 1482 1483 1484 1485 1486 1487 1488 1489234458 1490 1491 1492 1493 1494 1495 1496 1497 1498 US 2012 /0295815 A1 Nov . 22 , 2012 SO

ATGAAGTGAGAAATTGTTGAGAAGGATACAGTTTGTTTTTAGATGTCCTTTGTCCAATGTsmallnuclearribonucleoproteinpolypeptideE;SNRPE GTCAGGCCAGGGTCCTGTCTGCTCTGTGAGTCCCTCCAATTGTTCTTATTCCGAGATTTCpoly(ADP-ribose)polymerasefamily,member Genename/symbol AAGTGAAACAAACAAAAAGTGATGTCTGCCAACAGCCACCACCAAGACAAGCGTCTGGGTc-merprotooncogenetyrosinekinase;MERTK ANTIGEN-RELATED GGTGGAGACACAGCGGCTCCCCGCTAACCACCACTCTCCTGCCTGGTGTAGACAAAGCGGSODIUM/HYDROGENEXCHANGER7,9 GTCTACCCCCTGCACGTGCAGAGCAAAAAGAGCTTCCTATGGGAGCTGTTCTCCAGAAAAdisruptedinschizophrenia1;DISCI AAAATAGTTCAAATGAGTCCTGTATCATTGTATCTCCTATTCTGGATTAGTGCCTTTTGGhomeoboxcontaining1;HMBOX1 GAAAACATGGTAGGACTCACACTGGATAGAAACCAAAGCAGGTGAATCACCTGAGGTCAGzincfingerprotein763;ZNF763 9;PARP9 CCACCACCTCCACCCTGGAAGAGTTCCCCTTCCCTTTGAAATCTCATGGGACTTTGCCCCCLAUDIN-4 GCCGGGCAGAGGTGCTCCTCACTTGCCACACAGGGCGGCAGCTTGGCAGAGTCGCTCCTCHEPATOCELLULARCARCINOMA-ASSOCIATED TABLE5-continued Sequencesidentified CCTTTATTTCCTTTATTACCCGCATCCTTGTGTCACCAGGTCCTCTCATTACGACAGCCTunassigned TGTTCTCAGCACTGTACAACGGTCCCTATATAATACGGAGAAGCAATATCACTGTATGAGunassigned AAAAGATCGAAATGGACGAGCAGGATATGAGAAGGGCATTATATCGTTTCAGACTTACAGunassigned CAATGCTCTCCATCTCCCTTATGTGGACTCTTGTTCTTGTCTGATCTCTTGTCAAATTGTunassigned

occur.)oligonucleotideSequences

(Freq. of 100 100 100 100 100 100 100 100 100 100 100 100 100 237069 240102 264288 343450 423075 466085 510396 552912 660069 693356 700108 710021 710141 No./ABI SEQIDProbe No.ID Probe 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 1511 US 2012 /0295815 A1 Nov . 22 , 2012 96

Table 6 : Verification Results Using Same Platform but Per formed at a Different Laboratory and with a Different Sample TABLE 6B -continued Cohort Prediction performance TABLE 6A Study 2 Sample information Number of Number of samples Study 1 - probes present Frequency of Number of corresponding to Breast cancer samples 20 occurrence informative Accuracy study 1 informa- Accuracy Non -breast cancer samples 20 criterion probes estimated tive probes estimated 40 60 % 677 77. 95 653 85 . 0 70 % 645 78 . 74 625 85 . 0 80 % 606 78 . 74 589 77 . 5 90 % 538 80 . 31 524 80 . 0 TABLE 6B 100 % 282 72 .44 278 77 . 5 Prediction performance Table 7: Verification Results Using Different Platform Study 2 ( Codelink , GE ) and Performed at a Different Laboratory and Number of with a Different Sample Cohort Study 1 probes present TABLE 7A Frequency of Number of corresponding to occurrence informative Accuracy study 1 informa - Accuracy Sample information criterion probes estimated tive probes estimated Number of samples 0 % 1511 76 . 38 1466 82. 5 10 % 873 77. 17 842 80 . 0 Breast cancer samples 56 20 % 786 78 . 74 757 80 . 0 Non -breast cancer samples 58 30 % 748 80 . 31 722 82. 5 40 % 731 80 . 31 705 85 .0 114 50 % 707 78 . 74 682 85 . 0

TABLE 7B

Prediction performance Study 2 Study 3

Number of Number of Study 1 probes present probes present

Frequency of Number of corresponding to corresponding to occurrence informative Accuracy study 1 informa- Accuracy study 1 informa- Accuracy criterion probes estimated tive probes estimated tive probes estimated

0 % 1511 76 . 38 1466 82 . 5 611 80 . 70 10 % 873 77 . 17 842 80 . 0 507 80 . 70 20 % 786 78 .74 757 80 . 0 476 80 . 70 30 % 748 80 . 31 722 82 .5 467 80 .70 40 % 731 80 .31 705 85. 0 460 80 .70 50 % 707 78 . 74 682 85 . 0 446 80 .70 60 % 677 77 . 95 653 85 .0 435 79 . 82 70 % 645 78 . 74 625 85 . 0 425 78 .95 80 % 606 78 . 74 589 77 . 5 413 78 .95 90 % 538 80 .31 524 80 . 0 380 78 .95 100 % 282 72 .44 278 77 .5 213 71. 93