Program in Human Neutrophils Fails To

Home , Actinin alpha 2, ADCY3, ADCY7, Annexin A11, Annexin A7, APOBEC3A

Insights into Pathogen Immune Evasion Mechanisms: Anaplasma phagocytophilum Fails to Induce an Apoptosis Differentiation Program in Human Neutrophils This information is current as of September 25, 2021. Dori L. Borjesson, Scott D. Kobayashi, Adeline R. Whitney, Jovanka M. Voyich, Cynthia M. Argue and Frank R. DeLeo J Immunol 2005; 174:6364-6372; ; doi: 10.4049/jimmunol.174.10.6364 http://www.jimmunol.org/content/174/10/6364 Downloaded from

Supplementary http://www.jimmunol.org/content/suppl/2005/05/03/174.10.6364.DC1

Material http://www.jimmunol.org/ References This article cites 28 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/174/10/6364.full#ref-list-1

Why The JI? Submit online.

• Rapid Reviews! 30 days* from submission to initial decision by guest on September 25, 2021 • No Triage! Every submission reviewed by practicing scientists

• Fast Publication! 4 weeks from acceptance to publication

*average

Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts

The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology

Insights into Pathogen Immune Evasion Mechanisms: Anaplasma phagocytophilum Fails to Induce an Apoptosis Differentiation Program in Human Neutrophils1

Dori L. Borjesson,2* Scott D. Kobayashi,† Adeline R. Whitney,† Jovanka M. Voyich,† Cynthia M. Argue,* and Frank R. DeLeo†

Polymorphonuclear leukocytes (PMNs or neutrophils) are essential to human innate host defense. However, some bacterial pathogens circumvent destruction by PMNs and thereby cause disease. Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, survives within PMNs in part by altering normal host cell processes, such as production of reactive oxygen species (ROS) and apoptosis. To investigate the molecular basis of A. phagocytophilum survival within neutrophils, we used Affymetrix microarrays to measure global changes in human PMN gene expression following infection with A. phagocytophilum. Notably, A. Downloaded from phagocytophilum uptake induced fewer perturbations in host cell gene regulation compared with phagocytosis of Staphylococcus aureus. Although ingestion of A. phagocytophilum did not elicit significant PMN ROS, proinflammatory genes were gradually up-regulated, indicating delayed PMN activation rather than loss of proinflammatory capacity normally observed during phagocytosis-induced apoptosis. Importantly, ingestion of A. phagocytophilum failed to trigger the neutrophil apoptosis differentiation program that typically follows phagocytosis and ROS production. Heat-killed A. phagocytophilum caused some similar initial alterations in neutrophil gene expression and function, which included delaying normal PMN apoptosis and blocking Fas-induced http://www.jimmunol.org/ programmed cell death. However, at 24 h, down-regulation of PMN gene transcription may be more reliant on active infection. Taken together, these findings suggest two separate antiapoptotic processes may work concomitantly to promote bacterial survival: 1) uptake of A. phagocytophilum fails to trigger the apoptosis differentiation program usually induced by bacteria, and 2) a protein or molecule on the pathogen surface can mediate an early delay in spontaneous neutrophil apoptosis. The Journal of Immunology, 2005, 174: 6364–6372.

olymorphonuclear leukocytes (PMNs3 or neutrophils) are lum-infected PMNs suggest that the pathogen delays PMN apo- a first line of defense in the human innate immune re- ptosis (6, 7), minimizes proinflammatory cytokine release (8, 9), by guest on September 25, 2021 P sponse to bacterial pathogens. Most ingested bacteria are and inhibits and/or fails to activate ROS production (10–13). killed by the combined effects of PMN reactive oxygen species Mechanisms underlying the ability of A. phagocytophilum to in- (ROS) and cytotoxic granule components (1). However, some hibit production of PMN ROS are unclear (12–15). pathogens have evolved means to circumvent killing by PMNs and Recent studies indicate bacterial phagocytosis induces an apo- cause disease. The mechanisms used by pathogens to evade de- ptosis differentiation program in human PMNs that most likely struction by the innate immune system are incompletely contributes to the resolution of infections (16, 17). The apoptosis characterized. differentiation program is characterized by changes in a common Anaplasma phagocytophilum, the agent of human granulocytic set of genes triggered by uptake of bacteria or other particles that anaplasmosis, is an obligate intracellular bacterium known to sur- accelerate normal PMN apoptosis (16, 17). In contrast, A. phago- vive within PMNs (2, 3). A. phagocytophilum enters neutrophils cytophilum delays normal PMN apoptosis to facilitate productive primarily through a receptor-mediated endocytic pathway (4), and intracellular infection (6, 7). Inasmuch as induction of PMN apo- thus may ultimately reside in a modified endosomal compartment ptosis is regulated at the level of transcription (16–18), a compre- (5). Studies evaluating functional alterations in A. phagocytophi- hensive view of gene expression patterns in A. phagocytophilum- infected PMNs is critical to understanding processes that permit *Department of Veterinary Population Medicine, College of Veterinary Medicine, the pathogen to reside within PMNs. To that end, we studied University of Minnesota, St. Paul, MN 55108; and †Laboratory of Human Bacterial global gene expression in human PMNs during infection with A. Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infec- phagocytophilum. Our results suggest failure of A. phagocytophi- tious Diseases, Hamilton, MT 59840 lum to trigger the PMN apoptosis differentiation program and abil- Received for publication August 19, 2004. Accepted for publication March 2, 2005. ity of the organism to inhibit spontaneous neutrophil apoptosis are The costs of publication of this article were defrayed in part by the payment of page distinct processes that contribute to pathogen survival. charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 This work was supported in part by Grant AI-51529 (to D.L.B.) from the National Materials and Methods Institutes of Health. Materials 2 Address correspondence and reprint requests to Dr. Dori L. Borjesson, Department PLUS of Veterinary Population Medicine, College of Veterinary Medicine, University of Dextran T-500 and Ficoll-Paque (1.077 g/L) were purchased from Minnesota, 1365 Gortner Avenue, St. Paul, MN 55108. E-mail address: Amersham Biosciences. Sterile water ((Irrigation, United States Pharma- [email protected] copoeia (USP)) and 0.9% sodium chloride (Irrigation, USP) were obtained 3 Abbreviations used in this paper: PMN, polymorphonuclear leukocyte; BAX, B cell from Baxter Healthcare. PE-conjugated mAb specific for IL-1R antagonist line 2-associated X-protein; IL-1RN, IL-1R antagonist; ROS, reactive oxygen spe- (IL-1RN) (clone AS17) and isotype control mAb were purchased from BD cies; RPMI/H, RPMI 1640 medium buffered with 10 mM HEPES. Biosciences. RPMI 1640 medium was purchased from Invitrogen Life

Technologies. Unless indicated, all other reagents were obtained from incubator with 5% CO2 for up to 24 h. At the indicated times, medium was Sigma-Aldrich. aspirated and cells were washed with 500 ␮l of cold PBS and fixed with 4% paraformaldehyde on ice for 30 min. Fixative was aspirated, and cells Neutrophil isolation were washed with 500 ␮l of PBS. Uningested bacteria were then counter- Human PMNs were isolated from heparinized venous blood of healthy stained with anti-Alexa Fluor 488 Ab conjugated to Alexa Fluor 594 in 500 ␮ ␮ individuals with a widely used method (18). All studies with human blood l of PBS (7.5 g/ml final Ab concentration) (Molecular Probes) for 15 ␮ were performed in accordance with protocols approved by the Institutional min. Coverslips/Cells were washed twice in 500 l of PBS and mounted Review Board for Human Subjects at the University of Minnesota and the onto microscope slides with mounting medium (Aqua Polymount; Poly- National Institute of Allergy and Infectious Diseases. Blood was mixed 1:1 sciences). One hundred PMNs from random fields of view were evaluated with 0.9% sodium chloride (Baxter Healthcare) containing 3.0% Dextran at each time point, and ingested bacteria were scored using a fluorescence T-500 (Amersham) for 20 min at room temperature to sediment eryth- microscope (Nikon E800 microscope; Nikon). Bacteria stained with Alexa rocytes. The leukocyte-enriched supernatant was centrifuged at 670 ϫ g for Flour 488 (green only) were scored as ingested, and those stained with 10 min and resuspended in 35 ml of 0.9% sodium chloride. Ficoll- Alexa Fluor 488 and Alexa Fluor 594 were counted as uningested/surface PaquePLUS (10 ml) was pipetted carefully beneath the cell suspension and bound. The experiment was repeated using PMNs from three separate then centrifuged at 380 ϫ g for 25 min to separate PMNs from PBMCs. donors. PBMCs were removed by aspiration, sides of the tubes were swabbed, and Neutrophil ROS production erythrocytes were lysed with water (Irrigation USP; Baxter Healthcare) for 15–30 s, followed by immediate mixing with 1.7% sodium chloride. PMN ROS production was measured using a published fluorometric Purified PMNs were centrifuged at 380 ϫ g, resuspended in RPMI 1640 method (16, 21), but with modifications. Neutrophils were incubated with medium buffered with 10 mM HEPES, pH 7.4 (RPMI/H), and enumerated 25 ␮M2Ј,7Ј-dihydrodichlorofluorescein diacetate (Molecular Probes) for by microscopy. Purity of PMN preparations and cell viability were rou- 30–45 min at room temperature in RPMI/H. Subsequently, PMNs (106), tinely assessed by flow cytometry (FACSCalibur; BD Biosciences) or bacteria (ϳ1 ϫ 107 S. aureus or ϳ0.5–4 ϫ 107 live or heat-killed A. microscopy. The entire procedure was performed at room temperature, and phagocytophilum), or PMA (1–5 ␮g/ml) were combined in wells of a 96- Downloaded from cell preparations contained ϳ99% PMNs. Reagents used for neutrophil well microtiter plate at 4°C. The plates were centrifuged for 5 min at 380 ϫ purification typically contained Ͻ25.0 pg/ml endotoxin (Limulus amebo- g and immediately transferred to a microplate fluorometer (Spectamax cyte lysate assay; Fisher Scientific). Gemini; Molecular Devices). ROS production was measured for up to 120 min at 37°C with excitation and emission wavelengths of 485 and 538 nm, Growth of bacteria respectively. Vmax was calculated as the highest rate of ROS production A. phagocytophilum was isolated from a patient with human granulocytic within a 10-min time period using Softmax Pro version 3.1.2 (Molecular anaplasmosis in Nantucket, Massachusetts (NCH-1 isolate) (19). Patient Devices) (18). http://www.jimmunol.org/ blood (100 ␮l) was inoculated into SCID mice, as described (20). One drop Neutrophil apoptosis of mouse blood, collected ϳ3 wk after infection, was inoculated into HL60 cells (5 ϫ 105 cells/ml), which were cultured in IMDM containing 20% Neutrophil apoptosis was assessed by analysis of nuclear morphology (16)

heat-inactivated FBS at 37°C with 5% CO2, as described (20). Infected and or with a modified TUNEL assay (Apo-BrdU; BD Biosciences), as de- uninfected HL60 cells were counted and lysed using gentle sonication (3 scribed (15). Briefly, PMNs (2 ϫ 106) were plated directly into 24-well quick pulses at power 6, Model 100 Ultrasonic Dismembrator; Branson plates precoated with normal human serum and removed by aspiration at Ultrasonics). Host cell debris from each was removed by centrifugation the desired time point. Following interaction with live or heat-killed A. (2200 rpm for 5 min). The supernatant containing cell-free A. phagocyto- phagocytophilum, determination of PMN apoptosis by light microscopy philum or that from uninfected HL60 cells was centrifuged at 10,000 ϫ g was performed on cells stained with a modified Wright-Giemsa. Neutrophil ϳ

for 10 min to pellet bacteria. Pellet material containing A. phagocytophilum apoptosis was scored by morphological assessment of nuclei in 250 by guest on September 25, 2021 or that from uninfected HL60 lysate (negative control) was resuspended in PMNs per condition for each experiment. Alternatively, apoptosis was de- RPMI/H and immediately inoculated into cultures of human PMNs. Al- termined by DNA fragmentation in neutrophils following exposure to bac- ternatively, A. phagocytophilum (and control lysate) was heated for 10 min teria (described above) with a modified TUNEL assay, as described by the at 95°C and then inoculated into neutrophil cultures. Heat treatment of manufacturer (BD Biosciences). Samples (10,000 events each) were ana- Gram-positive bacteria at 95°C for 5 min has been shown to effectively kill lyzed using a FACSCalibur flow cytometer (BD Biosciences). In some all viable pathogens (16). These conditions (except that we heated for 10 experiments, 500 ng/ml anti-Fas mAb (clone CH-11; Upstate Biotechnol- min) also effectively killed A. phagocytophilum, as evidenced by their in- ogy) was added to PMN cultures 30 min after A. phagocytophilum. ability to infect or propagate within HL60 cells compared with freshly isolated, unheated A. phagocytophilum. All negative control samples (un- PMN gene expression and microarray analysis stimulated PMNs) were inoculated with clarified HL60 lysate from unin- PMN phagocytosis experiments were performed, as described previously fected cells that was prepared as described above. Thus, identical methods (18). In brief, PMNs (107) were combined on ice with live S. aureus (108) were used to prepare A. phagocytophilum and negative control HL60 or with live or heat-killed A. phagocytophilum (bacteria isolated from 5 ϫ lysates. 106 infected HL60 cells for a ratio of 1 infected HL60 cell:2 PMNs, ϳ5–20 Staphylococcus aureus strain COL was cultured at 37°C to mid-expo- A. phagocytophilum/PMN) in wells of a 12-well tissue culture plate (pre- ϭ nential phase of growth (OD600 0.75) in tryptic soy broth, as described coated with 20% autologous normal human serum). Unstimulated control (16). Bacteria were washed once with 1 ml of PBS and opsonized with assays received either buffer (for S. aureus comparisons) or clarified HL60 fresh 50% human serum for 30 min at 37°C, where indicated. Opsonized lysate prepared as described above (for A. phagocytophilum comparisons). S. aureus were washed twice with PBS and chilled on ice before use. Plates were centrifuged at 350 ϫ g for 8 min at 4°C to synchronize uptake Neutrophil uptake of A. phagocytophilum of bacteria and then incubated at 37°C with 5% CO2 for up to 24 h. Se- lection of the times at which gene expression was measured in A. phago- Uptake of bacteria by human PMNs was measured with a previously de- cytophilum-infected neutrophils (1.5, 3, 6, 9, 12, and 24 h) was based in scribed method (16, 18), but with modifications. Following isolation, part on previous experience with PMN gene expression and timing for PMNs were resuspended in RPMI/H at a concentration of 106 cells/ml. triggering of the apoptosis differentiation program (typically between 3 and Glass coverslips (12 mm round; presoaked in nitric acid and flamed with 6 h after PMN-pathogen interaction) (16, 18, 22-25). Inasmuch as apopto- ethanol) were placed into the wells of a 24-well tissue culture plate. Cov- sis was not triggered by A. phagocytophilum at early time points (1.5–6 h) erslips were coated with 100% autologous human serum at 37°C for 1 h and was significantly repressed by 24 h, these time points were of interest. and then washed twice with PBS. PMNs (3 ϫ 105 in 300 ␮l) were added The 9-h time point was selected for analysis of S. aureus-induced changes to each well and allowed to settle at room temperature for 15 min. Plates in gene expression because the apoptosis differentiation program is well were then chilled on ice. Bacteria isolated from infected HL60 cells (ratio underway at that time and because it was the time at which the greatest of 1 infected HL60 cell:2 PMNs, ϳ5–20 A. phagocytophilum per PMN) number of genes was differentially expressed by A. phagocytophilum (Fig. were resuspended in 1 ml of PBS containing 7.5 ␮g/ml Alexa Fluor 488 2) (16, 18). (Molecular Probes), and incubated for 15 min at room temperature. Stained At each time point, culture medium was aspirated from the plate and bacteria were washed twice with 1 ml of PBS to remove unbound Alexa PMNs were lysed with RLT buffer (Qiagen) supplemented with 2-ME. Fluor 488 and resuspended in RPMI/H. A total of 100 ␮l of Alexa Fluor Purification of PMN RNA and preparation of labeled cRNA target were 488-labeled A. phagocytophilum was added to each assay well, and plates performed, as described (16, 18, 22, 24, 25). Labeling of samples, hybrid- were centrifuged at 380 ϫ g for 8 min at 4°C to synchronize ingestion of ization of cRNA with HU133A oligonucleotide arrays (Affymetrix), and bacteria by PMNs. Culture plates were incubated at 37°C in a humidified GeneChip scanning (GeneArray 2500; Affymetrix) were performed with 6366 NEUTROPHIL RESPONSE TO A. phagocytophilum standard Affymetrix protocols (see www.affymetrix.com). Experiments quantified by fluorescence microscopy (Fig. 1, A and B). Com- were performed with PMNs from three healthy donors using a separate pared with phagocytosis typically observed for other bacteria (16), HU133A GeneChip (Affymetrix) for each donor. For experiments in Fig. there was relatively slow neutrophil uptake of A. phagocytophilum. 2, data were analyzed with Microarray Suite version 5.0 (Affymetrix) and Ϯ GeneSpring expression analysis software version 6.0 (Silicon Genetics), as However, most of the neutrophils (75.3 7.8%) contained in- described previously (16, 18, 22, 24, 25). For microarray experiments pre- gested bacteria 6 h after initiation of neutrophil-A. phagocytophi- sented in Figs. 3 and 4, data were analyzed with GeneChip Operating lum interaction (Fig. 1B). In addition, PMNs generally contained Software version 1.2 (Affymetrix), which replaced Microarray Suite version 5.0, and GeneSpring software version 7.0 (Silicon Genetics). Further- more, Affymetrix microarrays for the experiments presented in Fig. 2 were scanned on a GeneArray 2500 scanner (Affymetrix), whereas those in Figs. 3 and 4 were scanned on a new GeneChip Scanner 3000 (Affymetrix). Changes in gene expression were determined by comparing neutrophil transcript levels from samples stimulated with A. phagocytophilum or S. aureus with those from control, unstimulated cells. Briefly, genes identified as differentially expressed were called “Present” by GeneChip Operating Software version 1.2 (Affymetrix) in two of three individuals tested. The average fold change in gene expression was at least 1.5-fold for A. phagocytophilum-stimulated PMNs and/or 2.0-fold for those stimulated with S. aureus. Changes in PMN gene expression were also statistically significant in at least one of the pathogen treatments (at the level of p Յ 0.05, unpaired Student’s t test). A complete set of microarray results is published as supplemental Table I (first set of microarray experiments encompassing a 24-h Downloaded from time course after PMN uptake, plus S. aureus data at 9 h) and supplemental Table II (second set of microarray experiments that compare live and heat- killed A. phagocytophilum at 9 and 24 h), supplemental material.4 Raw and normalized microarray data are also posted online in the Gene Expression Omnibus (Ͻwww.ncbi.nim.nih.gov/geoϾ; accession no. GSE2405).

TaqMan real-time RT-PCR confirmation of microarray data http://www.jimmunol.org/ Phagocytosis experiments and RNA preparation for TaqMan analysis were performed with conditions identical with those used for microarray experiments (see above). DNA was removed from RNA samples by treatment with RNase-free DNase, as suggested by the manufacturer (Qiagen). RNA from three individuals was analyzed in duplicate wells with an ABI 7700 thermocycler (Applied Biosystems), as described (18). Primers and probe sets were designed with Primer Express version 1.5a and manufactured by Applied Biosystems. RNA was normalized using the Applied Biosystems predeveloped assay reagent for human ribosomal RNA. by guest on September 25, 2021 Flow cytometric evaluation of intracellular IL-1RN production Following uptake of A. phagocytophilum (described above), intracellular production of IL-1RN by human PMNs was measured with mAb AS17 conjugated to PE (BD Biosciences) using a previously described method (22). Briefly, staining for intracellular IL-1RN was performed 14 h following initial exposure to A. phagocytophilum in the presence of GolgiPlug (brefeldin A), added 6 h before measurements, as suggested by the manufacturer (BD Biosciences). The ability to detect intracellular IL-1RN is due to the capacity of brefeldin A (or GolgiPlug) to block endoplasmic reticulum-to-Golgi trafficking. The length of incubation with brefeldin A dictates in part the percentage of PMNs in which IL-1RN can be detected. The percentage of A. phagocytophilum-treated PMNs staining positive for intracellular IL-1RN was routinely 0–0.25% at 9 h, and this percentage increased significantly over time to 6–8% by 14 h. This significant increase is due to accumulating cytokine in the endoplasmic reticulum after treatment with GolgiPlug. Thus, it is likely that all PMNs constitutively produce IL-1RN, albeit not to detectable levels. Samples were analyzed with a FACSCalibur flow cytometer (BD Biosciences), and a single gate FIGURE 1. Interaction of A. phagocytophilum with human PMNs. A, was used to exclude autofluorescent cells and debris. Ingestion of A. phagocytophilum by human PMNs. Neutrophils were incubated with ϳ5–20 A. phagocytophilum/PMN for the indicated times, and Statistical analysis percentage of ingestion (number of PMNs containing internalized A. phagocytophilum) was determined by fluorescence microscopy. B, Micro- Statistics were performed with Student’s t test (Microsoft Excel 2002; Mi- graphs illustrating ingestion of A. phagocytophilum by human PMNs. crosoft) or one-way ANOVA with a Tukey’s or Bonferroni’s posttest for multiple comparisons (GraphPad Prism version 4.0 for Windows; Green, intracellular bacteria. Red or red-green (yellow), extracellular bac- GraphPad). teria. C, A. phagocytophilum fails to trigger significant PMN ROS production. op S.a., Serum-opsonized S. aureus (ϳ10 S. aureus/PMN); A.p. 0.5 ϳ ϳ Results ( 5–20 A. phagocyophilum/PMN); A.p. 1( 10–40 A. phagocyophilum/ PMN): ⌬A.p., heat-killed A. phagocytophilum. The V for PMN ROS Ingestion kinetics, ROS production, and apoptosis of max A. production was 20 min for S. aureus-activated cells and usually 70 min for phagocytophilum-infected human PMNs those exposed to A. phagocytophilum. D, A. phagocytophilum delays PMN To evaluate ingestion kinetics of A. phagocytophilum by human apoptosis. Neutrophils were incubated with live (left panel) or heat-killed PMNs in our assay system, pathogen uptake was visualized and (right panel) A. phagocytophilum (ϳ5–20 bacteria per PMN) for the indicated times, and apoptosis was determined by morphological assessment of nuclei. Results for A, C, and D are the mean Ϯ SEM of three to six separate 4 The online version of this article contains supplemental material. experiments. The Journal of Immunology 6367

FIGURE 2. Global changes in PMN gene expression following ingestion of A. phagocytophilum. A, Neutro- phil gene expression was measured with human oligonucleotide microarrays following ingestion of live A. phagocytophilum (ϳ5–20 bacteria per PMN). Data were analyzed with Mi- croarray Suite version 5.0 (Affymetrix) and GeneSpring software version 6.0 (Silicon Genetics, Redwood City, CA), as described (16, 18, 22, 24, 25). Dif- ferentially expressed genes were categorized based on known or putative function and enumerated. CC&GF, chemokines, cytokines, and growth fac-

tors; CAS&HD, cell adhesion and host Downloaded from defense; A&CF, apoptosis and cell fate; T&DB, transcription and DNA binding; M&VT, metabolism and vesicle traf- ﬁcking; R&ST, receptors and signal transduction; UNK, gene encoding proteins with unknown function. B, Mean

fold induction or repression of speciﬁc http://www.jimmunol.org/ human neutrophil genes following uptake of live A. phagocytophilum (A.p., ϳ5–20 bacteria per PMN) or S. aureus (S.a., ϳ10 bacteria per PMN) at the indicated time(s). Scale bar indicates fold increase or decrease in gene expression. In some instances, gene names are followed by the common name of the encoded protein. Where more than one Affymetrix probe set represented by guest on September 25, 2021 changes for a single gene, the number of probe sets is indicated in superscript. Results presented are the mean of three experiments (two or three blood donors with assays done on separate days). GF, growth factors. Olive shading indicates changes in gene expression generally similar between S. aureus and A. phagocytophilum.

high numbers of minimally degraded A. phagocytophilum (Fig. interaction (PMN apoptosis was inhibited 51.3 Ϯ 6.1% by live 1B). The relatively slow PMN uptake of A. phagocytophilum is bacteria and 52.8 Ϯ 9.7% by heat-killed organisms compared with consistent with a recent report by Carlyon et al. (13). spontaneous apoptosis noted in control PMNs) (Fig. 1D). The abil- We next evaluated generation of intracellular ROS by human ity of live A. phagocytophilum to delay neutrophil apoptosis di- PMNs during ingestion of A. phagocytophilum to determine minished by 48 h (57.7 Ϯ 2.9% of the cells were apoptotic after whether pathogen uptake activates neutrophils in our assay system infection with live organisms vs 70.1 Ϯ 10.5% for uninfected C (Fig. 1 ). As with previous studies (10, 11, 13), neither live nor cells; data not shown), indicating some of the processes underlying heat-killed pathogens elicited significant PMN ROS production the delay in neutrophil apoptosis occur early during infection. compared with either PMA or S. aureus (Fig. 1C). These findings These findings are consistent with reports by Yoshiie et al. and are consistent with an earlier report that demonstrated that inhibition of neutrophil superoxide generation is not dependent on viable Scaife et al. (6, 7) that suggest pathogen protein synthesis and/or or structurally intact bacteria (10). intracellular proliferation are not required for the observed anti- Bacterial phagocytosis normally induces neutrophil apoptosis apoptotic effect. The apoptosis differentiation program is typically (16, 23). In contrast, uptake of live or heat-killed A. phagocyto- triggered within hours of bacterial uptake (16, 23). Inasmuch as philum failed to induce neutrophil apoptosis (Fig. 1D). Spontane- there was a significant delay in neutrophil apoptosis 24 h after ous neutrophil apoptosis was also delayed significantly by live or infection (Fig. 1), we examined transcript levels in neutrophils at heat-killed organisms 24 h after initial A. phagocytophilum-PMN time points up to 24 h. 6368 NEUTROPHIL RESPONSE TO A. phagocytophilum

A. phagocytophilum induces global changes in PMN gene expression To gain insight into the molecular processes that permit survival of A. phagocytophilum within PMNs, we screened 14,500 human genes for changes in expression following ingestion of A. phagocytophilum (Fig. 2, and supplemental Table I).4 Compared with phagocytosis of S. aureus (Fig. 2) or other bacterial pathogens (16), ingestion of A. phagocytophilum induced far fewer changes in PMN gene expression (Figs. 2, A and B, and 3A). For example, 2,040 human genes were differentially regulated 9 h after phagocytosis of S. aureus by PMNs (Fig. 3A). By comparison, only 722 genes (35.4% of those altered by ingestion of S. aureus) were induced or repressed by A. phagocytophilum at the same time point (Fig. 3A). Previous work demonstrated that marked changes in PMN gene expression occur by 3–6 h after phagocytosis, and accompany induction of apoptosis and down-regulation of proinflammatory capacity (16, 22). The S. aureus strain COL used for comparison in this study has been shown to elicit this typical response (16). Thus, Downloaded from 24 h following interaction with S. aureus, neutrophils have under- gone apoptosis or primary necrosis and are no longer viable (our unpublished observations). By comparison, neutrophils containing ingested A. phagocytophilum 24 h after uptake were viable and had the greatest number of differentially regulated genes (1245) compared with any of the other times measured (Figs. 2A and 3, A and http://www.jimmunol.org/ B). This response included genes involved in the acute inflammatory response, such as those encoding TNF-␣, IL-1␤, IL-1⑀, IL-6, CXCL1, CXCL2, CXCL3, CCL3, CCL4, CCL20, CD54, IL-1RN, IL-1R1, and orosomucoid (Figs. 2A and 4). The patterns of gene regulation were also strikingly different between S aureus and A. phagocytophilum at 9 h postinfection (Fig. 2B). Notably, a significant number of genes that regulate apoptosis and signal transduction and encode structural proteins were down-regulated after by guest on September 25, 2021 phagocytosis of S. aureus, but remained unchanged following ingestion of A. phagocytophilum (Fig. 2B). Furthermore, many changes in PMN gene expression following ingestion of A. phagocytophilum were at variance with those in S. aureus-activated cells, or the time at which the change in expression occurred was delayed (Figs. 2A and 4). FIGURE 3. Changes in PMN gene expression following uptake of live and heat-killed A. phagocytophilum. A, Following bacteria-neutrophil in- Live and heat-killed pathogen-induced alterations in PMN gene teraction (ϳ10 S. aureus per PMN, or ϳ5–20 live or heat-killed A. phago- regulation cytophilum per PMN), neutrophil gene expression was measured with oligonucleotide microarrays. Numbers of differentially expressed genes at 9 h Live and nonviable (heat-killed) A. phagocytophilum had similar after bacteria-neutrophil interaction are compared between S. aureus, live capacities to delay neutrophil apoptosis, and each failed to elicit and heat-killed A. phagocytophilum (B). Numbers of differentially ex- generation of PMN ROS (Fig. 1, C and D). To test the hypothesis pressed genes 24 h after ingestion of live or heat-killed A. phagocytophilum that PMN gene regulation following uptake of live or heat-killed (C). Differentially expressed genes were categorized based on known or organisms is concomitantly similar, we performed a second set of putative function and enumerated, as described in the legend of Fig. 2. microarray experiments to directly compare the ability of live and Experiments were performed with PMNs from three healthy donors using heat-killed A. phagocytophilum to modulate human neutrophil a separate HU133A GeneChip for each donor. Data were analyzed with gene expression (Figs. 3 and 4, and supplemental Table II).4 Com- GeneChip Operating Software version 1.2 (Affymetrix) and GeneSpring pared with live pathogens at 9 or 24 h after uptake, interaction with software version 7.0 (Silicon Genetics, Redwood City, CA), as described in heat-killed A. phagocytophilum resulted in fewer alterations in Materials and Methods. Red bars, up-regulated genes; blue bars, down- regulated genes. PMN gene expression (Fig. 3). For example, 722 neutrophil genes were differentially regulated by live A. phagocytophilum 9 h after ingestion compared with 409 genes (56.7% of those altered by live PMN genes late during interaction with A. phagocytophilum may pathogens) induced or repressed by heat-killed bacteria (Fig. 3A). be reliant on active intracellular infection, a finding that merits At 9 h following ingestion of A. phagocytophilum, there was a further investigation (Fig. 3, B and C). In contrast, there was strik- proportional number of up- and down-regulated genes. At 24 h, ing similarity in the overall patterns of gene regulation within although the number of genes up-regulated by live and heat-killed functional categories between live and heat-killed A. phagocyto- A. phagocytophilum was generally similar (shared 72% of up-reg- philum (Fig. 4). Notably, there were large tracts of genes in all ulated genes) (Fig. 3B), there were far fewer genes down-regulated functional categories remaining unchanged after ingestion of live by heat-killed bacteria (only 8.3% of those down-regulated by live or dead A. phagocytophilum that were differentially regulated fol- bacteria) (Fig. 3C). These results suggest that down-regulation of lowing phagocytosis of S. aureus (Fig. 4). Thus, our data may The Journal of Immunology 6369

suggest that the majority of differences in PMN gene expression between live and heat-killed A. phagocytophilum are primarily in the time frame and magnitude of change.

Expression of genes encoding NADPH oxidase components Previous studies in promyelocytic HL60 cells suggest that the ability of A. phagocytophilum to inhibit ROS generation is linked to down-regulation of NADPH oxidase components (12–15). How- ever, this mechanism has not been demonstrated in human neutrophils. To that end, we analyzed all Affymetrix probe sets encoding NADPH oxidase proteins in our microarray data set (Table I). Genes encoding p47phox (NCF1), p40phox (NCF4), and Rap1A (RAP1A), regulators of NADPH oxidase, were down-regulated following phagocytosis of S. aureus (Fig. 2B). These genes, along with p67phox (NCF2), RAC2, and p22phox (CYBA), remained unchanged or were up-regulated after ingestion of A. phagocytophilum (Figs. 2B and 4, and Table I). Moreover, none of the genes encoding NADPH oxidase components, including CYBB (gp91phox) and CYBA (p22phox), were significantly down-regulated Downloaded from after A. phagocytophilum infection (Table I). These results clearly indicate that failure of A. phagocytophilum to elicit production of ROS by PMNs, or to block ROS production by a second stimulus, is not due to repression of genes encoding NADPH oxidase proteins, as previously suggested (12–15). http://www.jimmunol.org/ Regulation of inflammatory response mediators after A. phagocytophilum infection There were at least two general patterns of proinflammatory gene expression apparent in A. phagocytophilum-infected PMNs (Fig. 2). First, a group of genes encoding proinflammatory molecules, such as IL-1RN, TNF-␣, IL-6, IL-1␤, IL-1⑀, CCL20, IL-12␤, CCL3, CCL4, CXCL1, CXCL2, CD16, IL-13RA1, and CD18, was similarly up- or down-regulated by uptake of S. aureus and A. phagocytophilum (Figs. 2 and 4). However, induction or repression by guest on September 25, 2021 of many of these genes by A. phagocytophilum was blunted or delayed compared with that by S. aureus (Fig. 2). Second, there were genes for which expression was repressed following phagocytosis of S. aureus, but transcript levels were up-regulated or remained unchanged after ingestion of A. phagocytophilum. This category included genes encoding lymphotoxin B, TGF-␤1, IL-16, IL-17R, CD32, CD47, CD114 (G-CSF receptor), IL-1R2, MyD88, TLR4, leukocyte Ig-like receptors, STAT1, STAT3, STAT5B, STAT6, and formyl peptide receptor 1 (Fig. 2). These findings were confirmed by TaqMan real-time RT-PCR analysis, which was performed for six genes representative of the entire microarray data set and included three proinflammatory molecules (Fig. 5A). In addition, we used flow cytometry to confirm that IL-1RN protein accumulated following ingestion of A. phagocytophilum (Fig. 5B). The finding that A. phagocytophilum-infected PMNs retained proinflammatory capacity is consistent with the observation that the pathogen failed to induce neutrophil apoptosis.

A. phagocytophilum fails to induce an apoptosis differentiation program in human neutrophils A. phagocytophilum did not induce rapid PMN apoptosis that usually follows phagocytosis and ROS production (Fig. 1). As such, the expression of genes involved in apoptosis was examined FIGURE 4. Global changes in PMN gene expression following ingestion of live (A.p.) or heat-killed (⌬ A.p.) A. phagocytophilum or live S. aureus (S.a.) at the indicated times. Neutrophil gene expression data were analyzed with GeneChip Operating Software version 1.2 (Affymetrix), categorization of genes, olive shading, superscript numbers, and parenthet- which replaced Microarray Suite version 5.0 and GeneSpring software ver- ical annotation are described in the legend of Fig. 2. Results are presented sion 7.0 (Silicon Genetics, Redwood City, CA). Affymetrix microarrays as the mean fold induction or repression of genes from three experiments were scanned on a new GeneChip Scanner 3000 (Affymetrix). Functional (three blood donors with assays done on separate days). 6370 NEUTROPHIL RESPONSE TO A. phagocytophilum

Table I. Expression of NADPH oxidase components in human neutrophils following ingestion of A. phagocytophiluma

Fold change

Gene Name Live/HK Unigene Encoded Protein 1.5 h 3 h 6 h 9 h 12 h 24 h

CYBB1 Live A.p. Hs.88974 gp91phox nc nc nc nc nc 1.8 CYBB2 Live A.p. Hs.88974 gp91phox nc nc 1.6 nc nc 1.6 CYBB1 HK A.p. Hs.88974 gp91phox nc 1.8 CYBB2 HK A.p. Hs.88974 gp91phox nc 2.0 CYBA1 Live A.p. Hs.68877 p22phox nc nc nc nc nc 2.5 CYBA1 HK A.p. Hs.68877 p22phox nc 1.8* NCF11 Live A.p. Hs.458275 p47phox nc nc nc nc nc 2.0 NCF12 Live A.p. Hs.448231 p47phox nc nc nc nc nc 2.8 NCF11 HK A.p. Hs.1583 p47phox nc 2.1* NCF12 HK A.p. Hs.1583 p47phox nc 2.0* NCF21 Live A.p. Hs.949 p67phox nc nc Ϫ1.5 nc nc 1.9 NCF21 HK A.p. Hs.949 p67phox nc 1.7* NCF41 Live A.p. Hs.196352 p40 phox nc nc nc nc nc nc NCF42 Live A.p. Hs.196352 p40 phox nc nc nc nc nc 1.9 NCF41 HK A.p. Hs.196352 p40 phox 1.7 2.1* NCF42 HK A.p. Hs.196352 p40 phox nc 1.9 RAC21 Live A.p. Hs.301175 Rac2 nc nc nc nc nc nc Downloaded from RAC22 Live A.p. Hs.301175 Rac2 nc nc Ϫ1.8 nc nc 1.9 RAC21 HK A.p. Hs.301175 Rac2 1.5 2.5* RAC22 HK A.p. Hs.301175 Rac2 nc 1.9* RAP1A1 Live A.p. Hs.865 Rap1A nc Ϫ1.5 Ϫ1.7 nc nc nc RAP1A1 HK A.p. Hs.865 Rap1A nc 2.3*

a Live or heat-killed (HK) A. phagocytophilum was incubated with human PMNs for the indicated times, and expression of genes encoding NADPH oxidase proteins was measured with Affymetrix microarrays (HU133A), as described in Materials and Methods. Data are the mean fold change in genes from two or three individuals. The gene data http://www.jimmunol.org/ for infection with live organisms is derived from the ﬁrst set of microarray experiments. nc (no change), Gene failed to meet criteria for being differentially expressed (see Materials and Methods). HK, heat-killed A. phagocytophilum. *, p Ͻ 0.05 vs unstimulated (clariﬁed HL60 lysate-treated) PMNs. Superscript numbers indicate paired probe sets.

closely. Previous work has shown that many genes encoding ap- A. phagocytophilum inhibits Fas-induced PMN apoptosis optosis regulators are typically induced or repressed within 3–6 h Although our results explain the inability of A. phagocytophilum to after PMN phagocytosis (18). Notably, two such apoptosis regu- induce PMN apoptosis, it is not known whether the pathogen ac- lators, B cell line 2-associated X-protein (BAX) and nuclear or- by guest on September 25, 2021 tively blocks neutrophil death engaged by external stimuli. There- phan receptor TR3 (NR4A1), remained unchanged following up- fore, we tested the ability of live and heat-killed A. phagocytophi- take of A. phagocytophilum (18) (supplemental Tables I and II).4 lum to inhibit Fas-induced PMN apoptosis (Fig. 5C). Consistent Recently, we used PMNs from patients with chronic granuloma- with results in Fig. 1D, viable and nonviable A. phagocytophilum tous disease to demonstrate that ROS modulate expression of BAX inhibited Fas-induced cell death to similar degrees (inhibition of and are an important component of the PMN apoptosis differen- Fas-induced PMN apoptosis was 69.3 Ϯ 8.5% with live organisms tiation program induced by phagocytosis (24). Thus, our finding ( p Ͻ 0.001) and 68.3 Ϯ 9.5% with heat-killed organisms ( p Ͻ that A. phagocytophilum-infected PMNs do not elicit significant 0.01)) (Fig. 5C, left panel). These findings indicate that a pre- ROS production (Fig. 1C) most likely explains why expression of existing surface structure or protein promotes neutrophil survival BAX remained unchanged (data not shown). Genes encoding ap- during A. phagocytophilum infection, presumably to facilitate optotic protease-activating factor 1, BAX-inhibitor 1 (testis en- growth and replication of the pathogen. hanced gene transcript), B cell chronic lymphocytic leukemia/lymphoma 10, caspase 3, caspase 8, glucocorticoid receptor (NRC31), programmed cell death proteins 6 and 10, myeloid cell leukemia sequence 1, p21-activated kinase, JUN, tumor up-regulated Discussion caspase recruitment domain-containing antagonist of caspase 9, There is limited understanding of how bacterial pathogens evade TNF superfamily member 10, TNF receptor superfamily, member human innate host defense to cause disease. Inasmuch as neutro- 10B, and TNF receptor superfamily, member 1A-associated via phils are the most prominent innate immune effector cell in hu- death domain (TNFR-associated death domain protein), were in- mans, the ability of microorganisms to subvert PMN killing mech- duced or repressed after phagocytosis of S. aureus (Figs. 2 and 4). anisms is essential for pathogenesis. A. phagocytophilum fails to By contrast, these genes remained unchanged following uptake of trigger production of PMN ROS and delays neutrophil apoptosis, A. phagocytophilum or were at variance with changes in S. aureus thereby promoting pathogen survival within granulocytes (6, 7, (Figs. 2 and 4). Importantly, several antiapoptosis genes, including 10–15). Although progress has been made, the molecular basis for BIRC2, BIRC3, CFLAR, TNFAIP8, and TNIP2, were up-regulated A. phagocytophilum pathogenesis is not known. in PMNs after uptake of live or dead A. phagocytophilum (Fig. 4). To that end, we investigated global changes in human neutrophil These data are consistent with the ability of live or heat-killed A. gene expression following uptake of A. phagocytophilum and phagocytophilum to delay normal neutrophil apoptosis (Fig. 1D). gained new insight into pathogen survival mechanisms. First, we Taken together, the results indicate that A. phagocytophilum failed found that neutrophils infected with A. phagocytophilum gradually to induce the apoptosis differentiation program in human PMNs. up-regulated proinflammatory capacity, which peaked at 24 h Importantly, the data provide an underlying molecular basis for the postinfection, the latest time point studied. In contrast, there are inability of A. phagocytophilum to trigger PMN apoptosis. immediate (within 30 min) and dramatic increases in neutrophil The Journal of Immunology 6371

Second, our data clearly demonstrate that genes encoding components of NADPH oxidase, including gp91phox and Rac2, remain unchanged or are up-regulated in human neutrophils during A. phagocytophilum infection (Table I). These results are at variance with previous studies that suggest the inability of PMNs to produce ROS production following uptake of A. phagocytophilum is due to decreased gp91phox and/or Rac2 transcript levels (12, 14). How- ever, those studies were limited in scope and/or used HL60 cells rather than human PMNs (12, 14). HL60 cells are an immortalized cell line with significant differences in functional capacity compared with human neutrophils. Thus, the relevance of HL60 infection models to human disease is unclear. The inability of A. phagocytophilum to trigger generation of ROS may be due in part to uptake by host cell endocytosis rather than phagocytosis (4, 5, 28). In addition, recent data support alterations in NADPH oxidase assembly and superoxide scavenging as the basis for failure of the pathogen to directly elicit significant ROS production, findings most compatible with our current data (13).

Third, our results demonstrate that failure of A. phagocytophi- Downloaded from lum to induce the neutrophil apoptosis differentiation program in part underlies intracellular survival and represents a novel mechanism for pathogen immune evasion. As pathogen uptake also fails to elicit PMN ROS production, it may be that inability to induce the apoptosis differentiation program is secondary to the absence

of ROS production. This proposed mechanism is clearly distinct http://www.jimmunol.org/ from that underlying the ability of A. phagocytophilum to delay spontaneous neutrophil apoptosis or block Fas-induced cell death (Figs. 1D and 5C). It is possible that changes in expression of a gene or group of genes, such as induction of those encoding antiapoptosis molecules, contribute to these latter phenomena (Fig. 4 and Table I). Interestingly, live and heat-killed bacteria modulated early neutrophil processes (inhibition of apoptosis and failure to elicit ROS generation) to similar degrees. Moreover, patterns of PMN gene by guest on September 25, 2021 expression induced by heat-killed bacteria were in general similar FIGURE 5. Confirmation of microarray data and inhibition of Fas-in- to those induced by viable A. phagocytophilum, but generally dis- duced neutrophil apoptosis. A, TaqMan analysis of PMN gene expression. similar to the patterns induced by S. aureus (Figs. 2 and 4). This There was strong correlation (88.9%) between TaqMan and microarray observation suggests that there is an A. phagocytophilum-specific data. Results are the mean Ϯ SEM fold change in PMN transcript levels response, very different from that in bacteria studied to date (e.g., p Յ 0.05 vs unstimulated cells. B, Left panel, S. aureus), which most likely involves in part a bacterial surface ,ء .from three individuals Intracellular accumulation of neutrophil IL-1RN 14 h following ingestion structure or protein. The observation that a bacterial surface struc- of A. phagocytophilum. Right panel, Mean Ϯ SEM of five experiments. C, ture is sufficient to alter PMN function has been reported by others A. phagocytophilum inhibits neutrophil apoptosis triggered by anti-Fas (6, 10). At 9 h, over one-half of the genes differentially regulated mAb. Neutrophils were preincubated with live or heat-killed A. phagocy- by live A. phagocytophilum were similarly altered by heat-killed tophilum (ϳ5–20 bacteria per PMN), and then cultured with 500 ng/ml pathogen. At 24 h, up-regulated genes were, again, similar. Con- anti-Fas mAb, clone CH-11 for 6 h. ⌬A.p.or⌬lysate, A. phagocytophilum or clarified lysate from uninfected HL60 cells that was heated at 95°C for versely, interaction with heat-killed pathogen by 24 h resulted in 10 min. Apoptosis was measured with a modified TUNEL assay using a far fewer down-regulated genes compared with uptake of viable flow cytometer. Results are the mean Ϯ SEM of three experiments. organisms. Although the number of PMN genes down-regulated by live or dead A. phagocytophilum at 24 h represents a minor percentage of the overall gene expression data at that time point proinflammatory capacity following receptor-mediated phagocyto- (28.5%), these differences may suggest that living organisms are sis or ingestion of other bacterial pathogens, which (with receptor- necessary for ongoing functional alterations in PMNs infected with mediated phagocytosis) diminish dramatically by 24 h (16, 18, 22). A. phagocytophilum. Alternatively, this phenomenon may simply Our observation that there is a delay in proinflammatory gene up- be due to bacterial replication and the associated increase in bac- regulation may help bridge previous findings indicating an absence terial burden in viable infection compared with PMNs exposed to of PMN proinflammatory cytokine production (8, 9) with concur- nonviable organisms (29). Finally, heat killing or bacterial fixation, rent neutrophil activation and inflammatory disease (26, 27) during in and of itself, may alter the efficiency with which a surface struc- A. phagocytophilum infection. The delay in PMN proinflammatory ture or protein can modulate neutrophil function. In the end, the responses following infection with A. phagocytophilum might pro- observation that there are differences between live and heat-killed mote intracellular survival by limiting early neutrophil signaling A. phagocytophilum in numbers of down-regulated genes at 24 h and recruitment/activation of other immune cells. Furthermore, re- still fails to explain the similar capacity of each to block apoptosis tention of proinflammatory capacity in A. phagocytophilum-in- within that same time frame (Fig. 1). Thus, the mechanisms by fected cells is consistent with the observation that the pathogen which PMN functions are altered by long-term (Ͼ24-h) infection fails to induce PMN apoptosis. with A. phagocytophilum warrant additional study. 6372 NEUTROPHIL RESPONSE TO A. phagocytophilum

Based on our current studies and other recent reports, the ability 10. Mott, J., and Y. Rikihisa. 2000. Human granulocytic ehrlichiosis agent inhibits of bacteria to alter normal PMN apoptosis is most likely a com- superoxide anion generation by human neutrophils. Infect. Immun. 68: 6697–6703. ponent of pathogenesis (23). Importantly, our study suggests that 11. Wang, T., S. E. Malawista, U. Pal, M. Grey, J. Meek, M. Akkoyunlu, V. Thomas, failure of A. phagocytophilum to induce the neutrophil apoptosis and E. Fikrig. 2002. Superoxide anion production during Anaplasma phagocytophila infection. J. Infect. Dis. 186: 274–280. differentiation program and concomitant ability to delay/block 12. Carlyon, J. A., W. T. Chan, J. Galan, D. Roos, and E. Fikrig. 2002. Repression PMN apoptosis represent two separate mechanisms used by A. of rac2 mRNA expression by Anaplasma phagocytophila is essential to the in- phagocytophilum to prolong pathogen survival. Prolonged patho- hibition of superoxide production and bacterial proliferation. J. Immunol. 169: 7009–7018. gen survival permits ongoing PMN exposure to a host of patho- 13. Carlyon, J. A., D. Abdel-Latif, M. Pypaert, P. Lacy, and E. Fikrig. 2004. genic mechanisms. The combined strategies implemented by A. Anaplasma phagocytophilum utilizes multiple host evasion mechanisms to thwart phagocytophilum to prolong neutrophil survival may thus repre- NADPH oxidase-mediated killing during neutrophil infection. Infect. Immun. 72: 4772–4783. sent a general mechanism used by obligate intracellular pathogens 14. Banerjee, R., J. Anguita, D. Roos, and E. Fikrig. 2000. Cutting edge: infection by to evade human innate host defense, thereby contributing to dis- the agent of human granulocytic ehrlichiosis prevents the respiratory burst by down-regulating gp91phox. J. Immunol. 164: 3946–3949. ease. Notably, our studies provide a global view of the host-patho- 15. Mott, J., Y. Rikihisa, and S. Tsunawaki. 2002. Effects of Anaplasma phagocy- gen interface important for our understanding of human diseases tophila on NADPH oxidase components in human neutrophils and HL-60 cells. caused by intracellular bacteria. Infect. Immun. 70: 1359–1366. 16. Kobayashi, S. D., K. R. Braughton, A. R. Whitney, J. M. Voyich, T. G. Schwan, J. M. Musser, and F. R. DeLeo. 2003. Bacterial pathogens modulate an apoptosis Acknowledgments differentiation program in human neutrophils. Proc. Natl. Acad. Sci. USA 100: 10948–10953. We thank Kelly O’Donnell for technical assistance. 17. Kobayashi, S. D., and F. R. DeLeo. 2004. An apoptosis differentiation pro- gramme in human polymorphonuclear leukocytes. Biochem. Soc. Trans. 32: Downloaded from 474–476. Disclosures 18. Kobayashi, S. D., J. M. Voyich, C. L. Buhl, R. M. Stahl, and F. R. DeLeo. 2002. The authors have no ﬁnancial conﬂict of interest. Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: cell fate is regulated at the level of gene expression. Proc. Natl. Acad. Sci. USA 99: 6901–6906. References 19. Telford, S. R., III, J. E. Dawson, P. Katavolos, C. K. Warner, C. P. Kolbert, and 1. Jones, S., F. Lindberg, and E. Brown. 2003. Phagocytosis. In Fundamental Im- D. H. Persing. 1996. Perpetuation of the agent of human granulocytic ehrlichiosis

munology. W. E. Paul, ed. Lippincott Williams & Wilkins, Philadelphia, p. 997– in a deer tick-rodent cycle. Proc. Natl. Acad. Sci. USA 93: 6209–6214. http://www.jimmunol.org/ 1020. 20. Hodzic, E., J. W. Ijdo, S. Feng, P. Katavolos, W. Sun, C. H. Maretzki, D. Fish, 2. Chen, S. M., J. S. Dumler, J. S. Bakken, and D. H. Walker. 1994. Identification E. Fikrig, S. R. Telford III, and S. W. Barthold. 1998. Granulocytic ehrlichiosis of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. in the laboratory mouse. J. Infect. Dis. 177: 737–745. J. Clin. Microbiol. 32: 589–595. 21. DeLeo, F. R., L. A. Allen, M. Apicella, and W. M. Nauseef. 1999. NADPH 3. Dumler, J. S., A. F. Barbet, C. P. Bekker, G. A. Dasch, G. H. Palmer, S. C. Ray, oxidase activation and assembly during phagocytosis. J. Immunol. 163: Y. Rikihisa, and F. R. Rurangirwa. 2001. Reorganization of genera in the families 6732–6740. Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of 22. Kobayashi, S. D., J. M. Voyich, K. R. Braughton, and F. R. DeLeo. 2003. Down- some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrli- regulation of proinflammatory capacity during apoptosis in human polymorpho- chia with Neorickettsia, descriptions of six new species combinations and des- nuclear leukocytes. J. Immunol. 170: 3357–3368. ignation of Ehrlichia equi and ‘HGE agent’ as subjective synonyms of Ehrlichia 23. DeLeo, F. R. 2004. Modulation of phagocyte apoptosis by bacterial pathogens. phagocytophila. Int. J. Syst. Evol. Microbiol. 51: 2145–2165. Apoptosis 9: 399–413.

4. Herron, M. J., C. M. Nelson, J. Larson, K. R. Snapp, G. S. Kansas, and 24. Kobayashi, S. D., J. M. Voyich, K. R. Braughton, A. R. Whitney, W. M. Nauseef, by guest on September 25, 2021 J. L. Goodman. 2000. Intracellular parasitism by the human granulocytic ehrli- H. L. Malech, and F. R. DeLeo. 2004. Gene expression profiling provides insight chiosis bacterium through the P-selectin ligand, PSGL-1. Science 288: into the pathophysiology of chronic granulomatous disease. J. Immunol. 172: 1653–1656. 636–643. 5. Webster, P., J. W. IJdo, L. M. Chicoine, and E. Fikrig. 1998. The agent of human 25. Kobayashi, S. D., J. M. Voyich, G. A. Somerville, K. R. Braughton, granulocytic ehrlichiosis resides in an endosomal compartment. J. Clin. Invest. H. L. Malech, J. M. Musser, and F. R. DeLeo. 2003. An apoptosis-differentiation 101: 1932–1941. program in human polymorphonuclear leukocytes facilitates resolution of inflam- 6. Yoshiie, K., H. Y. Kim, J. Mott, and Y. Rikihisa. 2000. Intracellular infection by mation. J. Leukocyte Biol. 73: 315–322. the human granulocytic ehrlichiosis agent inhibits human neutrophil apoptosis. 26. Borjesson, D. L., S. I. Simon, E. Hodzic, H. E. DeCock, C. M. Ballantyne, and ␤ Infect. Immun. 68: 1125–1133. S. W. Barthold. 2003. Roles of neutrophil 2 integrins in kinetics of bacteremia, 7. Scaife, H., Z. Woldehiwet, C. A. Hart, and S. W. Edwards. 2003. Anaplasma extravasation, and tick acquisition of Anaplasma phagocytophila in mice. Blood phagocytophilum reduces neutrophil apoptosis in vivo. Infect. Immun. 71: 101: 3257–3264. 1995–2001. 27. Choi, K. S., D. J. Grab, and J. S. Dumler. 2004. Anaplasma phagocytophilum 8. Klein, M. B., S. Hu, C. C. Chao, and J. L. Goodman. 2000. The agent of human infection induces protracted neutrophil degranulation. Infect. Immun. 72: granulocytic ehrlichiosis induces the production of myelosuppressing chemo- 3680–3683. kines without induction of proinflammatory cytokines. J. Infect. Dis. 182: 28. Mott, J., R. E. Barnewall, and Y. Rikihisa. 1999. Human granulocytic ehrlichiosis 200–205. agent and Ehrlichia chaffeensis reside in different cytoplasmic compartments in 9. Kim, H. Y., and Y. Rikihisa. 2000. Expression of interleukin-1␤, tumor necrosis HL-60 cells. Infect. Immun. 67: 1368–1378. factor ␣, and interleukin-6 in human peripheral blood leukocytes exposed to 29. Branger, S., J. M. Rolain, and D. Raoult. 2004. Evaluation of antibiotic suscep- human granulocytic ehrlichiosis agent or recombinant major surface protein P44. tibilities of Ehrlichia canis, Ehrlichia chaffeensis, and Anaplasma phagocytophi- Infect. Immun. 68: 3394–3402. lum by real-time PCR. Antimicrob. Agents Chemother. 48: 4822–4828. Supplemental Material for the JI Website

Table I. Neutrophil genes differentially regulated following ingestion of S. aureus and/or A. phagocytophilum.

Gene name Probe set Unigene Encoded protein or homolog Sa 9 Ap 1.5 Ap 3 Ap 6 Ap 9 Ap 12 Ap 24

A. phagocytophilum & S. aureus (shared) Metabolism & vesicle trafficking Up-regulated (41) ACAT2 209608_s_at Hs.278544 acetyl-Coenzyme A acetyltransferase 2 1.7 2.0 AMPD3 207992_s_at Hs.83918 adenosine monophosphate deaminase (isoform E) 2.4 1.8 ARFGAP3 202211_at Hs.13014 ADP-ribosylation factor GTPase activating protein 3 3.4 2.1 ATP1B1 201242_s_at Hs.78629 ATPase, Na+/K+ transporting 3.4 1.6 -2.6 B4GALT5 221485_at Hs.107526 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase 3.5 2.5 B4GALT5 221484_at Hs.107526 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase 3.1 2.4 CLCN7 38069_at Hs.80768 chloride channel 7 5.2 1.7 1.5 1.8 CLIC4 201560_at Hs.25035 chloride intracellular channel 4 3.2 2.2 1.7 1.7 3.8 CLN2 200742_s_at Hs.20478 ceroid-lipofuscinosis, neuronal 2 2.2 1.6 1.7 2.1 CLN2 200743_s_at Hs.20478 ceroid-lipofuscinosis, neuronal 2 2.8 1.5 1.7 CLN2 214196_s_at Hs.20478 ceroid-lipofuscinosis, neuronal 2 2.0 1.7 1.9 2.1 DNAJC8 205545_x_at Hs.433540 DnaJ (Hsp40) homolog 2.0 1.6 FDX1 203646_at Hs.744 ferredoxin 1 2.3 1.7 GCH1 204224_s_at Hs.86724 GTP cyclohydrolase 1 5.4 1.7 2.1 2.3 3.6 GCLC 202923_s_at Hs.151393 glutamate-cysteine ligase, catalytic subunit 5.7 1.7 -2.4 GCLC 202922_at Hs.151393 glutamate-cysteine ligase, catalytic subunit 4.2 -2.2 GCLM 203925_at Hs.89709 glutamate-cysteine ligase, modifier subunit 2.5 1.7 2.7 2.5 2.0 GGTLA4 211416_x_at Hs.355394 gamma-glutamyltransferase-like activity 4 2.1 1.8 HSPA1B 202581_at Hs.274402 heat shock 70kDa protein 1B 4.1 2.2 HS3ST2 219697_at Hs.115830 heparan sulfate 3-O-sulfotransferase 2 2.1 2.1 INSIG1 201625_s_at Hs.56205 insulin induced gene 1 4.3 1.5 2.0 2.0 1.8 INSIG1 201626_at Hs.56205 insulin induced gene 1 5.5 2.1 1.7 1.9 INSIG1 201627_s_at Hs.56205 insulin induced gene 1 4.3 2.1 2.6 2.1 2.4 KCNB1 211006_s_at Hs.84244 potassium voltage-gated channel 2.4 2.0 KCNB1 211006_s_at Hs.84244 potassium voltage-gated channel 2.4 KCNJ14 220776_at Hs.144011 potassium inwardly-rectifying channel 2.4 1.5 1.7 -2.3 MGLL 211026_s_at Hs.6721 monoglyceride lipase 6.5 1.9 1.8 1.7 1.8 M6PR 200901_s_at Hs.134084 mannose-6-phosphate receptor 4.6 1.6 1.5 1.5 2.4 PDXK 202671_s_at Hs.38041 pyridoxal kinase 6.2 1.6 1.5 4.3 PDXK 218018_at Hs.4746 pyridoxal kinase 4.3 1.7 2.0 1.6 PEX3 203972_s_at Hs.7277 peroxisomal biogenesis factor 3 3.0 4.5 -1.5 PFDN4 205362_s_at Hs.91161 prefoldin 4 2.3 2.4 1.5 1.6 -3.2 PFKFB3 202464_s_at Hs.195471 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 2.1 1.7 1.6 PPIF 201489_at Hs.173125 peptidylprolyl isomerase F 5.4 2.7 PPIF 201490_s_at Hs.173125 peptidylprolyl isomerase F 5.4

1 PTGS2 204748_at Hs.196384 prostaglandin-endoperoxide synthase 2 5.2 1.9 2.1 2.3 2.5 RAB20 219622_at Hs.179791 RAB20, member RAS oncogene family 3.1 1.5 2.4 2.0 1.6 RHAG 206145_at Hs.169536 Rhesus blood group-associated glycoprotein 2.9 2.7 SCAMP1 206668_s_at Hs.31218 secretory carrier membrane protein 1 2.7 2.0 -1.8 -1.6 SCAMP1 212425_at Hs.31218 secretory carrier membrane protein 1 2.8 SCAMP1 206667_s_at Hs.31218 secretory carrier membrane protein 1 2.4 -2.9 SEC22L1 214257_s_at Hs.50785 SEC22 vesicle trafficking protein-like 1 3.1 -2.1 1.5 2.2 SEC22L1 209206_at Hs.50785 SEC22 vesicle trafficking protein-like 1 2.1 SEC22L1 209207_s_at Hs.50785 SEC22 vesicle trafficking protein-like 1 2.5 SEC24A 212900_at Hs.211612 SEC24 related gene family 2.6 2.7 SEC24A 212902_at Hs.211612 SEC24 related gene family 3.7 1.5 SLC4A4 210739_x_at Hs.5462 sodium bicarbonate cotransporter 2.4 SLC4A4 203908_at Hs.5462 sodium bicarbonate cotransporter 2.5 SLC4A4 203908_at Hs.5462 sodium bicarbonate cotransporter 2.5 2.4 SLC4A7 209884_s_at Hs.132904 sodium bicarbonate cotransporter 2.6 -2.2 SLC6A14 219795_at Hs.162211 neurotransmitter transporter 2.0 1.5 SLC11A2 203124_s_at Hs.57435 proton-coupled divalent metal ion transporter 35.9 1.7 1.8 1.6 4.3 SLC11A2 203123_s_at Hs.57435 proton-coupled divalent metal ion transporter 3.6 1.5 SLC43A3 210692_s_at Hs.274453 solute carrier family 43, member 3 14.1 2.1 1.8 1.7 1.6 1.9 SLC43A3 213113_s_at Hs.274453 solute carrier family 43, member 3 6.5 1.7 1.9 1.6 1.8 SOD2 215078_at Hs.372783 superoxide dismutase 2, mitochondrial 89.5 2.4 1.5 1.8 1.8 SOD2 216841_s_at Hs.372783 superoxide dismutase 2, mitochondrial 4.4 2.1 SOD2 215223_s_at Hs.372783 superoxide dismutase 2, mitochondrial 3.4 2.5 SOD2 221477_s_at Hs.177781 superoxide dismutase 2, mitochondrial 2.1 STX4A 203530_s_at Hs.83734 syntaxin 4A (placental) 2.2 2.1 TBC1D2 222173_s_at Hs.135917 TBC1 domain family, member 2 13.4 1.9 1.6 2.4 UBE3A 211575_s_at Hs.180686 ubiquitin protein ligase E3A 2.4 1.5 -2.0 UBE3A 211285_s_at Hs.180686 ubiquitin protein ligase E3A 1.3 -1.7

Down-regulated (41) ABCA7 219577_s_at Hs.134514 ATP-binding cassette -2.7 -1.6 ABHD2 63825_at Hs.5258 abhydrolase domain containing 2 -30.3 -2.0 ABHD2 221815_at Hs.412022 abhydrolase domain containing 2 -12.2 -1.7 ABHD5 213805_at Hs.19385 abhydrolase domain containing 5 -5.1 -1.6 -1.8 ABHD5 218739_at Hs.19385 abhydrolase domain containing 5 -3.1 -1.7 -2.3 -1.8 AGTPBP1 204500_s_at Hs.21542 ATP/GTP binding protein 1 -2.7 -1.5 -1.8 AMPD2 212360_at Hs.82927 adenosine monophosphate deaminase 2 -8.4 -2.1 -1.7 ATPIF1 218671_s_at Hs.241336 ATPase inhibitory factor 1 -9.1 -1.6 ATP5J 202325_s_at Hs.73851 ATP synthase, H+ transporting -11.0 -1.6 CABC1 218168_s_at Hs.273186 chaperone, ABC1 activity of bc1 complex like -9.4 -2.1 CSAD 221139_s_at Hs.279815 cysteine sulfinic acid decarboxylase -2.4 -1.7 -1.9 CSNK1G2 202573_at Hs.181390 casein kinase 1, gamma 2 -3.1 -1.5 -2.0 DPEP2 219452_at Hs.115537 dipeptidase 2 -142.7 -4.9 -2.1 2.5 ELOVL5 208788_at Hs.250175 ELOVL family member 5 -4.1 -1.6 FBXO9 212987_at Hs.11050 F-box only protein 9 -2.6 -1.6 FBXO11 203255_at Hs.284289 F-box only protein 11 -8.9 -1.5 2.0 FBXO11 222119_s_at Hs.284289 F-box only protein 11 -2.7 GALNT3 203397_s_at Hs.278611 UDP-N-acetyl-alpha-D-galactosamine -9.6 -2.4 GLRX 206662_at Hs.28988 glutaredoxin (thioltransferase) -7.3 -1.6 2.4

2 GLRX 209276_s_at Hs.28988 glutaredoxin (thioltransferase) -4.9 HAL 217521_at Hs.276590 histidine ammonia-lyase -3.6 -2.2 HAL 206643_at Hs.276590 histidine ammonia-lyase -6.0 -1.7 HAL 217521_at Hs.276590 histidine ammonia-lyase -3.6 IDS 212221_x_at Hs.303154 iduronate 2-sulfatase (Hunter syndrome) -5.8 -1.5 IDS 210666_at Hs.172458 iduronate 2-sulfatase (Hunter syndrome) -17.1 IDS 202439_s_at Hs.172458 iduronate 2-sulfatase (Hunter syndrome) -3.0 -1.5 IDS 212223_at Hs.303154 iduronate 2-sulfatase (Hunter syndrome) -6.2 IDS 206342_x_at Hs.172458 iduronate 2-sulfatase (Hunter syndrome) -14.7 3.0 KIF1B 209234_at Hs.375193 kinesin family member 1B -6.7 -2.1 KPNB2 209225_x_at Hs.168075 karyopherin (importin) beta 2 -4.9 -1.7 -1.5 KPNB2 209226_s_at Hs.168075 karyopherin (importin) beta 2 -2.0 KPNB2 221829_s_at Hs.168075 karyopherin (importin) beta 2 -4.7 LPIN2 202460_s_at Hs.166318 lipin 2 -2.8 -2.0 -1.8 LPIN2 202459_s_at Hs.166318 lipin 2 -5.1 LRMP 204674_at Hs.40202 lymphoid-restricted membrane protein -17.8 -1.7 LRMP 35974_at Hs.40202 lymphoid-restricted membrane protein -79.2 -1.7 -2.2 -1.5 1.6 MME 203434_s_at Hs.1298 membrane metallo-endopeptidase -19.6 -1.8 -2.1 MME 203435_s_at Hs.1298 membrane metallo-endopeptidase -17.2 -1.6 MPPE1 209858_x_at Hs.154145 metallo phosphoesterase -23.8 -4.1 MPPE1 213727_x_at Hs.154145 metallo phosphoesterase -20.6 -2.1 -2.3 MPPE1 209858_x_at Hs.154145 metallo phosphoesterase -23.8 MPPE1 206764_x_at Hs.154145 metallo phosphoesterase -17.8 NACA 200735_x_at Hs.32916 nascent-polypeptide-associated complex alpha -2.7 -1.6 NACA 208635_x_at Hs.32916 nascent-polypeptide-associated complex alpha -2.1 -1.5 NARF 219862_s_at Hs.256526 nuclear prelamin A recognition factor -13.2 -1.6 -1.7 -1.7 NDUFB6 203613_s_at Hs.109646 NADH dehydrogenase (ubiquinone) subcomplex -22.8 -1.7 -1.6 NSFL1C 217831_s_at Hs.12865 NSFL1 (p97) cofactor (p47) -22.7 -1.8 NSFL1C 220248_x_at Hs.284261 NSFL1 (p97) cofactor (p47) -3.2 PSME2 201762_s_at Hs.433810 proteasome activator subunit 2 -3.4 -1.9 2.7 RNPEP 208270_s_at Hs.283667 arginyl aminopeptidase (aminopeptidase B) -7.9 -1.9 -1.6 RPL30 209203_s_at Hs.330988 ribosomal protein L30 -2.7 -1.6 -1.8 SEC14L1 202083_s_at Hs.75232 SEC14-like 1 (S. cerevisiae) -4.8 -1.7 -2.0 2.5 SEC14L1 202084_s_at Hs.75232 SEC14-like 1 (S. cerevisiae) -3.7 SEC14L1 202082_s_at Hs.75232 SEC14-like 1 (S. cerevisiae) -4.9 SEPX1 217977_at Hs.279623 selenoprotein X, 1 -63.0 -1.5 2.5 SLC19A1 211576_s_at Hs.84190 folate transporter -8.2 -2.1 -2.1 -1.7 SLC21A11 219229_at Hs.14805 organic anion transporter -68.2 -1.5 -1.8 3.0 SMURF2 205596_s_at Hs.194477 E3 ubiquitin ligase SMURF2 -2.0 -1.8 -1.6 STX10 212625_at Hs.43812 syntaxin 10 -9.7 -1.6 TKT 208700_s_at Hs.89643 transketolase -14.1 -2.1 -1.8 -1.6 TKT 208699_x_at Hs.89643 transketolase -11.1 -1.7 -2.2 TRPC4AP 212059_s_at Hs.168073 transient receptor potential cation channel -3.2 -1.8 -1.7 1.8 VAMP3 201336_at Hs.66708 vesicle-associated membrane protein 3 -21.2 -1.5 2.4 VNN2 205922_at Hs.121102 vanin 2 -15.2 -2.2 -1.6 1.9

Cytokines, chemokines, & growth factors Up-regulated (17) CCL3 205114_s_at Hs.73817 MIP1A, SCYA3 44.7 1.6 4.2

3 CCL4 204103_at Hs.75703 MIP1B, SCYA4 15.5 4.3 CCL20 205476_at Hs.75498 MIP3A,SCYA20 158.8 2.1 7.0 11.7 7.5 CXCL1 204470_at Hs.789 GRO1, GROa, SCYB1, 7.7 3.5 CXCL2 209774_x_at Hs.75765 GRO2, GROb, MIP2A, SCYB2 86.9 1.5 2.0 2.9 3.2 3.3 CXCL3 207850_at Hs.89690 GRO3, GROg, MIP2B, SCYB3 21.6 3.2 3.4 1.7 3.4 EREG 205767_at Hs.115263 epiregulin 2.6 1.9 HGF 210755_at Hs.809 hepatocyte growth factor 2.8 -1.6 1.6 -2.4 IFNA10 208261_x_at Hs.282275 interferon, alpha 10 2.1 1.6 -2.4 IL1F9 220322_at Hs.211238 interleukin 1 family, member 9 6.3 2.6 5.6 5.0 3.3 4.9 IL1B 205067_at Hs.126256 interleukin 1, beta 5.0 1.6 2.2 4.1 IL1B 39402_at Hs.126256 interleukin 1, beta 5.5 1.6 1.9 3.7 IL6 205207_at Hs.93913 interleukin 6 (interferon, beta 2) 1.8 1.7 3.2 7.1 10.3 4.7 2.9 IL8 202859_x_at Hs.624 interleukin 8 2.9 -2.8 1.7 IL8 211506_s_at variant (IL8) mRNA, complete cds 4.3 -2.3 2.6 IL12B 207901_at Hs.674 interleukin 12B 3.2 2.1 3.5 1.7 OSM 214637_at Hs.248156 oncostatin M 20.1 2.4 2.3 TNF 207113_s_at Hs.241570 tumor necrosis factor 3.6 1.9 2.5 3.1 2.3 2.3 2.2 VEGF 212171_x_at Hs.73793 vascular endothelial growth factor 10.9 1.7 1.9 VEGF 211527_x_at Hs.73793 vascular endothelial growth factor 13.1 2.5 2.2 1.6 1.5 VEGF 210512_s_at Hs.73793 vascular endothelial growth factor 26.5 1.5 VEGF 210513_s_at Hs.73793 vascular endothelial growth factor 2.6

Cell adhesion & host defense Up-regulated (17) AQP9 205568_at Hs.104624 aquaporin 9 3.0 -2.0 3.4 CD44 204489_s_at Hs.169610 CD44 antigen 3.3 2.1 CD44 204490_s_at Hs.169610 CD44 antigen 5.2 2.6 CD44 217523_at Hs.169610 CD44 antigen 6.3 2.6 1.6 2.0 CD44 209835_x_at Hs.169610 CD44 antigen 7.0 1.7 1.6 3.4 CD44 210916_s_at Hs.306278 CD44 antigen 4.6 1.6 2.1 2.8 CD44 212014_x_at Hs.169610 CD44 antigen 5.7 1.7 1.6 3.0 CD44 212063_at Hs.169610 CD44 antigen 3.1 CD48 204118_at Hs.901 CD48 antigen 5.1 1.5 2.0 2.1 CSTB 201201_at Hs.695 cystatin B (stefin B) 6.3 2.2 C3 217767_at Hs.284394 complement component 3 48.2 1.8 1.6 1.5 3.3 DNAH7 214222_at Hs.97403 dynein, axonemal, heavy polypeptide 7 2.8 1.6 -2.5 ICAM1 202637_s_at Hs.168383 intercellular adhesion molecule 1 (CD54) 3.1 2.2 ICAM1 202638_s_at Hs.168383 intercellular adhesion molecule 1 (CD54) 3.1 1.5 1.6 1.5 2.7 ORM1 205040_at Hs.572 orosomucoid 1 59.1 1.6 1.8 1.7 2.4 2.9 17.2 ORM1 205041_s_at Hs.572 orosomucoid 1 37.5 1.8 2.3 3.2 11.3 PKP2 207717_s_at Hs.25051 plakophilin 2 2.0 1.5 -2.2 PI3 41469_at Hs.112341 protease inhibitor 3, skin-derived (SKALP) 8.9 -2.0 2.3 PI3 203691_at Hs.112341 protease inhibitor 3, skin-derived (SKALP) 11.5 -2.3 2.7 PTX3 206157_at Hs.2050 pentaxin-related gene 2.6 1.9 2.3 1.6 PLAU 205479_s_at Hs.77274 plasminogen activator, urokinase 15.6 2.1 PLAU 211668_s_at Hs.77274 plasminogen activator, urokinase 9.9 2.3 1.9 1.7 1.6 1.5 SERPINB9 209723_at Hs.104879 serine (or cysteine) proteinase inhibitor 7.7 2.0 2.3 SLPI 203021_at Hs.251754 secretory leukocyte protease inhibitor 3.3 1.7 2.5 SPINK1 206239_s_at Hs.181286 serine protease inhibitor, Kazal type 1 14.1 1.5 2.2 2.0 3.3

4 SPINLW1 206318_at Hs.121084 serine protease inhibitor-like (eppin) 2.2 -2.4 1.6 -2.3 SNN 218033_s_at Hs.76691 stannin 2.9 2.9 SNN 218032_at Hs.76691 stannin -1.1 3.0

Down-regulated (12) ADD3 201753_s_at Hs.324470 adducin 3 (gamma) -3.8 -1.5 ADD3 201752_s_at Hs.324470 adducin 3 (gamma) -2.2 -1.6 ADD3 201034_at Hs.324470 adducin 3 (gamma) -4.7 DIAPH1 213514_s_at Hs.432623 diaphanous homolog 1 (Drosophila) -3.5 -1.8 -2.9 DIAPH1 209190_s_at Hs.432623 diaphanous homolog 1 (Drosophila) -4.3 DGCR2 214198_s_at Hs.2491 DiGeorge syndrome critical region gene 2 -9.0 -2.9 -1.6 -1.6 FLII 212025_s_at Hs.83849 flightless I homolog (Drosophila) -8.3 -1.6 HRIHFB2122 210276_s_at Hs.40342 Tara-like protein -3.1 -2.5 HRIHFB2122 202795_x_at Hs.40342 Tara-like protein -2.1 HRIHFB2122 216210_x_at Hs.40342 Tara-like protein -1.9 -1.6 ITGAL 213475_s_at Hs.174103 CD11a antigen -9.0 -2.1 -2.0 LYZ 213975_s_at Hs.234734 lysozyme (renal amyloidosis) -3.4 -2.0 MRLC2 221474_at Hs.233936 myosin regulatory light chain -3.3 -3.3 -1.7 2.2 PECAM1 208981_at Hs.78146 CD31 antigen -35.2 -1.5 -2.3 -1.7 PECAM1 208982_at Hs.78146 CD31 antigen -12.1 -2.3 -2.7 -1.6 PECAM1 208983_s_at Hs.78146 CD31 antigen -49.1 -2.3 -3.9 -1.9 RNASE6 213566_at Hs.23262 ribonuclease -8.1 -2.9 WAS 205400_at Hs.2157 Wiskott-Aldrich syndrome -4.3 1.5 -2.0 WAS 38964_r_at Hs.2157 Wiskott-Aldrich syndrome -2.5 ZYX 200808_s_at Hs.75873 zyxin -4.2 -2.1

Receptors and signal transduction Up-regulated (40) ADCY3 209321_s_at Hs.8402 adenylate cyclase 3 3.3 1.8 -2.3 ADCY3 209320_at Hs.8402 adenylate cyclase 3 3.1 ADRA1A 211489_at Hs.52931 adrenergic, alpha-1A-, receptor 3.2 1.9 ANXA5 200782_at Hs.300711 annexin A5 3.8 1.7 1.5 1.9 ARHGAP11A 204492_at Hs.172652 similar to human GTPase-activating protein 2.6 2.0 ARHGAP11A 204492_at Hs.172652 similar to human GTPase-activating protein 2.6 BAGE 207712_at Hs.2355 B melanoma antigen 4.3 1.5 -4.5 6.5 2.3 -2.5 CCRL2 211434_s_at Hs.302043 chemokine (C-C motif) receptor-like 2 41.0 1.6 3.5 CREM 209967_s_at Hs.155924 cAMP responsive element modulator 5.1 2.0 CREM 207630_s_at Hs.155924 cAMP responsive element modulator 3.4 CREM 214508_x_at Hs.155924 cAMP responsive element modulator 4.5 DUSP10 221563_at Hs.177534 dual specificity phosphatase 10 3.5 1.5 1.5 1.6 2.0 EHD4 209536_s_at Hs.55058 EH-domain containing 4 2.1 2.2 1.9 FAD104 218618_s_at Hs.299883 FAD104 4.3 2.3 FCER1G 204232_at Hs.433300 IgE receptor 2.7 -1.5 2.5 FGR 208438_s_at Hs.1422 v-fgr oncogene homolog 2.0 2.5 HRH4 221169_s_at Hs.287388 histamine receptor H4 2.4 -1.9 2.1 -2.1 IFI30 201422_at Hs.14623 interferon, gamma-inducible protein 30 4.7 -2.0 2.5 IL1R1 202948_at Hs.82112 interleukin 1 receptor, type I 3.3 1.7 IL1RN 212657_s_at Hs.81134 interleukin 1 receptor antagonist 18.4 1.6 3.4 IL1RN 216243_s_at Hs.81134 interleukin 1 receptor antagonist 3.2 1.6 1.5 2.1 2.7 2.5

5 IL1RN 212659_s_at Hs.81134 interleukin 1 receptor antagonist 10.2 1.6 1.7 2.4 2.0 2.2 2.9 IRS1 204686_at Hs.96063 insulin receptor substrate 1 2.7 2.2 ITPR1 216944_s_at Hs.198443 inositol 1,4,5-triphosphate receptor 4.1 2.6 2.7 1.8 ITPR1 203710_at Hs.198443 inositol 1,4,5-triphosphate receptor 4.8 1.5 1.6 2.4 2.3 2.0 LEPR 209894_at Hs.226627 leptin receptor 2.9 2.3 LEPR 211356_x_at Hs.226627 leptin receptor 2.3 MAPK6 207121_s_at Hs.271980 MAP kinase 6 7.7 2.1 2.3 1.8 1.6 MAP3K8 205027_s_at Hs.248 MAP kinase kinase kinase 8 2.3 1.7 2.1 2.1 2.3 MAP4K4 206571_s_at Hs.3628 MAP kinase kinase kinase kinase 4 8.6 2.7 OR1D2 221464_at Hs.247936 olfactory receptor 2.2 2.5 3.1 PHLDA1 217996_at Hs.82101 pleckstrin homology-like domain 2.6 2.8 2.1 PHLDA1 217997_at Hs.82101 pleckstrin homology-like domain 3.1 1.8 PLA2G4A 210145_at Hs.211587 phospholipase A2, group IVA 2.1 -2.0 1.6 PLEK 203471_s_at Hs.77436 pleckstrin 2.3 2.6 PPAP2B 212226_s_at Hs.432840 phosphatidic acid phosphatase type 2B 8.5 1.7 1.7 2.1 2.4 2.2 PPAP2B 209355_s_at Hs.432840 phosphatidic acid phosphatase type 2B 52.5 2.1 2.2 3.0 3.0 5.0 PPAP2B 212230_at Hs.432840 phosphatidic acid phosphatase type 2B 8.9 1.6 1.8 2.0 1.9 2.0 PSG1 210195_s_at Hs.405968 CD66f 2.1 1.5 -2.0 PTK2 207821_s_at Hs.740 PTK2 protein tyrosine kinase 2 2.3 -1.6 6.1 PTPN13 204201_s_at Hs.211595 protein tyrosine phosphatase 2.7 3.4 P2RX4 204088_at Hs.321709 purinergic receptor P2X 3.3 2.0 2.5 2.9 1.9 1.6 RALGDS 209051_s_at Hs.106185 ral guanine nucleotide dissociation stimulator 14.8 1.9 1.6 3.3 RALGDS 209050_s_at Hs.106185 ral guanine nucleotide dissociation stimulator 8.9 RHOBTB3 216049_at Hs.10432 Rho-related BTB domain containing 3 2.5 2.0 -2.7 SCARB2 201647_s_at Hs.323567 scavenger receptor class B, member 2 2.1 1.6 -2.0 SH3BP5 201811_x_at Hs.109150 SH3-domain binding protein 5 4.7 -1.6 2.5 SH3BP5 201810_s_at Hs.109150 SH3-domain binding protein 5 4.0 SPHK1 219257_s_at Hs.68061 sphingosine kinase 1 7.0 1.6 2.2 2.1 2.5 2.5 SQSTM1 213112_s_at Hs.182248 sequestosome 1 12.1 1.7 1.6 1.7 1.5 4.0 TFRC 208691_at Hs.77356 transferrin receptor (p90, CD71) 12.6 1.9 2.5 2.2 1.8 TFRC 207332_s_at Hs.77356 transferrin receptor (p90, CD71) 8.5 3.1 4.0 2.8 TNFAIP6 206025_s_at Hs.29352 TNF, alpha-induced protein 6 4.1 -1.8 3.6 TNFAIP6 206026_s_at Hs.29352 TNF, alpha-induced protein 6 3.9 -2.0 2.3 TPTE 220205_at Hs.122986 transmembrane phosphatase 3.3 -2.0 2.2 -2.6

Down-regulated (45) ABAT 209459_s_at Hs.283675 4-aminobutyrate aminotransferase -8.8 -2.0 -2.0 ARHGAP4 204425_at Hs.3109 Rho GTPase activating protein 4 -3.8 -2.2 ARPC4 217817_at Hs.323342 ARP 2/3 complex, subunit 4, 20kDa -4.8 -1.6 2.1 ARPC4 211672_s_at Hs.323342 ARP 2/3 complex, subunit 4, 20kDa -3.5 AUP1 220525_s_at Hs.173736 ancient ubiquitous protein 1 -12.9 -1.9 1.6 BTK 205504_at Hs.159494 Bruton agammaglobulinemia tyrosine kinase -2.9 -1.5 BTN2A1 211256_x_at Hs.169963 butyrophilin, subfamily 2, member A1 -2.2 -1.6 2.3 BTN2A1 203944_x_at Hs.169963 butyrophilin, subfamily 2, member A1 -2.6 BTN2A1 215493_x_at Hs.169963 butyrophilin, subfamily 2, member A1 -2.2 BTN3A2 212613_at Hs.87497 butyrophilin, subfamily 3, member A2 -23.4 -2.6 BTN3A2 212613_at Hs.87497 butyrophilin, subfamily 3, member A2 -23.4 BTN3A2 209846_s_at Hs.87497 butyrophilin, subfamily 3, member A2 -11.9 -1.7 CAMK2G 212757_s_at Hs.12436 CaM kinase II gamma -6.0 -2.1 -1.9

6 CAMK2G 214322_at Hs.12436 CaM kinase II gamma -9.8 -2.2 CAMK2G 214322_at Hs.12436 CaM kinase II gamma -9.8 CAMK2G 212669_at Hs.12436 CaM kinase II gamma -3.7 DCL-1 203799_at Hs.2441 type I transmembrane C-type lectin -16.3 -1.6 -2.2 FCGR3A 204007_at Hs.176663 CD16 -5.9 -2.3 -1.6 -1.5 FCGR3A 204006_s_at Hs.372679 CD16 -18.7 -2.0 FPR1 205119_s_at Hs.753 formyl peptide receptor 1 -2.3 -1.7 2.6 FPR1 205118_at Hs.753 formyl peptide receptor 1 -3.6 F2RL1 213506_at Hs.154299 coagulation factor II (thrombin) receptor-like 1 -7.2 -1.9 -1.7 GMIP 218913_s_at Hs.49427 Gem-interacting protein -15.9 -1.8 2.7 HA-1 212873_at Hs.196914 minor histocompatibility antigen HA-1 -10.0 -2.1 -2.5 -1.8 IFRD1 202147_s_at Hs.7879 interferon-related developmental regulator 1 -5.0 -2.2 -1.6 IFRD1 202146_at Hs.7879 interferon-related developmental regulator 1 -4.7 IL1R2 205403_at Hs.25333 interleukin 1 receptor, type II -2.7 -1.7 3.3 IL1R2 211372_s_at Hs.25333 interleukin 1 receptor, type II -3.0 IL8RA 207094_at Hs.194778 interleukin 8 receptor, alpha -17.0 -1.7 -3.3 -2.0 IL8RB 207008_at Hs.846 interleukin 8 receptor, beta -19.0 -1.9 -2.6 -1.5 IL13RA1 201888_s_at Hs.285115 interleukin 13 receptor, alpha 1 -18.1 -2.6 -1.6 -1.8 IL13RA1 201887_at Hs.285115 interleukin 13 receptor, alpha 1 -2.8 IMPA2 203126_at Hs.5753 inositol(myo)-1(or 4)-monophosphatase 2 -29.4 -2.1 -2.9 INPPL1 201598_s_at Hs.75339 inositol polyphosphate phosphatase-like 1 -2.9 -2.1 INPP4A 204552_at Hs.379860 inositol polyphosphate-4-phosphatase, type I -11.8 1.5 -2.4 1.5 INPP5D 203332_s_at Hs.155939 inositol polyphosphate-5-phosphatase -3.6 -1.9 -1.9 ITPK1 210740_s_at Hs.6453 inositol 1,3,4-triphosphate 5/6 kinase -5.8 -1.7 JIK 220761_s_at Hs.12040 STE20-like kinase -22.8 -1.8 -1.7 1.5 LILRA1 210660_at Hs.166156 leukocyte Ig-like receptor -18.6 -2.1 LILRA2 207857_at Hs.94498 leukocyte Ig-like receptor -4.9 -1.9 -2.1 -1.6 LILRA2 211100_x_at Hs.94498 leukocyte Ig-like receptor -3.6 LILRA2 211101_x_at Hs.94498 leukocyte Ig-like receptor -5.1 -1.5 MAP3K3 203514_at Hs.29282 MAP kinase kinase kinase 3 -4.7 -2.8 -2.0 -1.9 PAK1 209615_s_at Hs.64056 p21/Cdc42/Rac1-activated kinase 1 -2.8 1.5 -1.6 -2.4 PINK1 209019_s_at Hs.6163 PTEN induced putative kinase 1 -4.0 -1.7 PINK1 209018_s_at Hs.6163 PTEN induced putative kinase 1 -2.5 PLCL2 213309_at Hs.54886 phospholipase C-like 2 -25.2 -2.6 PLCL2 216218_s_at Hs.54886 phospholipase C-like 2 -6.4 -3.1 -1.6 PLEKHE1 212719_at Hs.38176 pleckstrin homology domain contaning -2.9 -3.4 PTK9L 202009_at Hs.6780 PTK9L protein tyrosine kinase 9-like -2.5 -1.5 PTPN2 213136_at Hs.82829 protein tyrosine phosphatase -10.6 -1.6 -1.6 RALBP1 202844_s_at Hs.75447 ralA binding protein 1 -14.0 -1.8 2.0 RALBP1 202845_s_at Hs.75447 ralA binding protein 1 -7.2 RPS6KA1 204633_s_at Hs.149957 ribosomal protein S6 kinase -4.6 -1.6 -1.5 1.6 RPS6KA5 204635_at Hs.109058 ribosomal protein S6 kinase -7.4 -2.1 -1.6 RPS6KA5 202449_s_at Hs.109058 ribosomal protein S6 kinase -2.1 RXRA 202388_at Hs.20084 retinoid X receptor, alpha -3.6 -1.7 RGS2 203379_at Hs.78944 regulator of G-protein signalling 2 -4.2 -2.2 -1.6 SORL1 203509_at Hs.101657 sortilin-related receptor -8.3 -2.0 -1.7 SORL1 212560_at Hs.82845 sortilin-related receptor -11.3 SNARK 220987_s_at Hs.172012 SNF1/AMP-activated protein kinase -3.5 -1.6 TAPBP-R 218747_s_at Hs.267993 TAP binding protein related -2.3 -4.2 -4.6

7 TLR1 210176_at Hs.2474 toll-like receptor 1 -7.5 -1.5 -1.5 -1.6 1.6 TXNIP 201008_s_at Hs.179526 thioredoxin interacting protein -7.0 -1.5 TXNIP 201009_s_at Hs.179526 thioredoxin interacting protein -3.8 TXNIP 201010_s_at Hs.179526 thioredoxin interacting protein -3.5 ULK1 209333_at Hs.47061 unc-51-like kinase 1 (C. elegans) -8.0 -1.6 -2.0

Apoptosis and cell fate Up-regulated (23) ADORA2A 205013_s_at Hs.1613 adenosine A2a receptor 15.2 3.4 BCL3 204908_s_at Hs.31210 B-cell CLL/lymphoma 3 3.3 2.3 BCL11A 219497_s_at Hs.130881 B-cell CLL/lymphoma 11A 2.8 4.0 1.6 -1.6 BTG3 213134_x_at Hs.77311 BTG family, member 3 3.0 2.0 1.6 2.3 CASP2 34449_at Hs.108131 caspase 2 2.0 1.7 GADD45B 207574_s_at Hs.110571 growth arrest and DNA-damage-inducible, beta 11.8 1.5 2.7 GADD45B 209304_x_at Hs.110571 growth arrest and DNA-damage-inducible, beta 9.1 2.0 3.3 GADD45B 213560_at Hs.110571 growth arrest and DNA-damage-inducible, beta 8.0 -2.0 4.1 GADD45B 209305_s_at Hs.110571 growth arrest and DNA-damage-inducible, beta 5.7 G0S2 213524_s_at Hs.432132 putative lymphocyte G0/G1 switch gene 20.0 2.3 IER3 201631_s_at Hs.76095 immediate early response 3 3.0 -1.9 3.1 IER5 218611_at Hs.15725 immediate early response 5 2.2 2.1 INHBA 210511_s_at Hs.727 inhibin, beta A 136.2 2.7 3.4 3.1 JAG1 216268_s_at Hs.91143 jagged 1 (Alagille syndrome) 2.6 2.7 2.8 2.9 3.5 LIMS1 212687_at Hs.193700 LIM and senescent cell antigen-like domains 1 9.7 2.5 LIMS1 207198_s_at Hs.112378 LIM and senescent cell antigen-like domains 1 5.0 -1.5 MADH4 202526_at Hs.75862 mothers against decapentaplegic homolog 4 2.9 3.3 1.8 -2.0 MADH4 202527_s_at Hs.75862 mothers against decapentaplegic homolog 4 -2.1 NFKBIA 201502_s_at Hs.81328 NFKB inhibitor, alpha 4.8 -2.2 2.7 NR4A3 216979_at Hs.80561 nuclear receptor subfamily 4, group A, member 3 2.3 1.6 NR4A3 207978_s_at Hs.80561 nuclear receptor subfamily 4, group A, member 3 4.4 NSMAF 203269_at Hs.78687 N-SMase activation associated factor 2.8 2.1 PHLDA2 209803_s_at Hs.154036 pleckstrin homology-like domain 21.2 1.7 2.2 2.1 1.9 PPP1R15A 202014_at Hs.76556 protein phosphatase 1, regulatory subunit 15A 9.8 1.6 1.6 3.9 PPP1R15A 37028_at Hs.76556 protein phosphatase 1, regulatory subunit 15A 7.2 1.5 1.7 2.5 TLR2 204924_at Hs.63668 toll-like receptor 2 2.9 1.7 1.6 2.9 TNFAIP3 202644_s_at Hs.211600 TNF, alpha-induced protein 3 4.0 3.2 TNFAIP3 202643_s_at Hs.211600 TNF, alpha-induced protein 3 4.3 2.4 TNFSF14 207907_at Hs.129708 TNF (ligand) superfamily, member 14 3.7 2.7 TNFSF15 221085_at Hs.241382 TNF (ligand) superfamily, member 15 8.9 1.8 1.8 TRAF1 205599_at Hs.2134 TNF receptor-associated factor 1 5.1 1.5 1.7 1.6 1.6 2.2

Down-regulated (11) ACINUS 201715_s_at Hs.227133 apoptotic chromatin condensation inducer in the nucleus -6.5 -2.1 1.9 CHES1 205022_s_at Hs.211773 checkpoint suppressor 1 -10.2 -1.6 -1.8 CPR8 214152_at Hs.82506 cell cycle progression 8 protein -3.0 -2.0 -1.7 CPR8 221511_x_at Hs.82506 cell cycle progression 8 protein -1.7 -1.7 FOXO3A 204131_s_at Hs.380831 forkhead box O3A -4.8 -1.7 FOXO3A 210655_s_at Hs.14845 forkhead box O3A -29.7 -2.7 FOXO3A 204132_s_at Hs.380831 forkhead box O3A -2.7 FRAT1 219889_at Hs.126057 frequently rearranged in advanced T-cell lymphomas -3.2 -1.7 -1.7

8 MKL1 212748_at Hs.31146 megakaryoblastic leukemia (translocation) 1 -3.9 -1.7 -2.2 RAD21 200608_s_at Hs.81848 RAD21 homolog (S. pombe) -3.8 -1.6 SIPA1 204164_at Hs.7019 signal-induced proliferation-associated gene 1 -7.8 -1.6 -1.6 2.9 STK17A 202693_s_at Hs.9075 serine/threonine kinase 17a (apoptosis-inducing) -6.4 -1.7 TACC3 218308_at Hs.104019 transforming, acidic coiled-coil containing protein 3 -32.5 -4.9 -5.3 TUSC2 203273_s_at Hs.8186 tumor suppressor candidate 2 -3.1 -1.5 -1.6 1.6

Transcription and DNA binding Up-regulated (14) ATF5 204998_s_at Hs.9754 activating transcription factor 5 2.7 1.6 EGR3 206115_at Hs.74088 early growth response 3 7.0 2.2 -1.6 ETS2 201328_at Hs.395762 v-ets oncogene homolog 2 (avian) 3.7 1.5 2.0 2.0 2.1 2.0 ETS2 201329_s_at Hs.85146 v-ets oncogene homolog 2 (avian) 5.6 1.8 1.9 2.0 1.8 2.9 ETS2 222303_at Hs.292477 v-ets oncogene homolog 2 (avian) 3.2 1.7 1.9 2.3 1.6 MAF 205193_at Hs.51305 v-maf oncogene homolog F (avian) 7.4 1.8 2.0 1.6 MAF 36711_at Hs.51305 v-maf oncogene homolog F (avian) 20.0 1.7 1.7 1.6 2.7 MAF 209348_s_at Hs.30250 v-maf oncogene homolog F (avian) 2.1 1.8 RAD51L3 37793_r_at Hs.125244 RAD51-like 3 (S. cerevisiae) 2.3 2.3 -2.3 SALL1 206893_at Hs.123094 sal-like 1 (Drosophila) 2.7 1.8 -2.1 2.6 1.5 TFEC 206715_at Hs.374709 transcription factor EC 4.7 2.3 2.8 2.4 2.1 TLK1 211077_s_at Hs.18895 tousled-like kinase 1 4.0 2.4 -1.6 TSC22 215111_s_at Hs.114360 TGF-beta-stimulated protein TSC-22 2.1 1.5 2.2 1.6 WTAP 214759_at Hs.119 Wilms' tumour 1-associating protein 2.1 2.2 1.9 WTAP 203137_at Hs.119 Wilms' tumour 1-associating protein 4.7 1.6 1.6 1.6 1.9 WTAP 210285_x_at Hs.119 Wilms' tumour 1-associating protein 5.3 1.9 2.0 1.9 3.8 XBP1 200670_at Hs.149923 X-box binding protein 1 4.9 1.7 2.3 ZFYVE26 37943_at Hs.8663 zinc finger, FYVE domain containing 26 3.4 1.7 ZFYVE26 213073_at Hs.8663 zinc finger, FYVE domain containing 26 4.5 2.1 ZNF216 217649_at Hs.406096 zinc finger protein 216 2.2 1.8 ZNF337 37860_at Hs.139240 zinc finger protein 337 2.5 1.6

Down-regulated (23) ATF1 222103_at Hs.36908 activating transcription factor 1 -13.6 -1.7 -1.5 2.5 CREB5 205931_s_at Hs.149 cAMP responsive element binding -13.5 -2.8 CIRBP 200810_s_at Hs.119475 cold inducible RNA binding protein -11.6 -1.5 2.0 FLI1 204236_at Hs.108043 Friend leukemia virus integration 1 -4.0 -1.8 -2.1 HHEX 204689_at Hs.118651 hematopoietically expressed homeobox -2.9 -1.6 -1.9 -1.6 -1.5 -1.7 HHEX 215933_s_at Hs.118651 hematopoietically expressed homeobox -5.0 -1.7 MGRN1 212576_at Hs.284251 mahogunin, ring finger 1 -3.1 -1.5 MKRN1 209845_at Hs.7838 makorin, ring finger protein, 1 -9.0 -1.6 2.1 MKRN1 201285_at Hs.7838 makorin, ring finger protein, 1 -2.8 MLL4 203419_at Hs.92236 myeloid/lymphoid or mixed-lineage leukemia 4 -7.9 -1.8 1.7 MNDA 204959_at Hs.153837 myeloid cell nuclear differentiation antigen -9.8 -1.9 -1.9 -1.6 NFATC3 210555_s_at Hs.172674 nuclear factor of activated T-cells, C3 -38.6 -2.8 -1.6 PBX2 202875_s_at Hs.93728 pre-B-cell leukemia transcription factor 2 -3.0 -1.8 RERE 221643_s_at Hs.194369 arginine-glutamic acid dipeptide (RE) repeats -2.4 -2.2 -1.6 RERE 200940_s_at Hs.194369 arginine-glutamic acid dipeptide (RE) repeats -6.4 RNASET2 217984_at Hs.8297 ribonuclease T2 -6.5 -1.5 -2.1 -1.6 RUVBL1 201613_s_at Hs.272822 RuvB-like 1 (E. coli) -11.3 -2.2 -1.6 1.8

9 SLBP 206052_s_at Hs.75257 stem-loop (histone) binding protein -5.8 -1.6 -1.7 SMARCA5 202303_x_at Hs.9456 actin dependent regulator of chromatin -9.9 2.1 -1.5 SMARCA5 213859_x_at Hs.9456 actin dependent regulator of chromatin -4.2 S100A11 200660_at Hs.417004 calgizzarin -5.3 -1.6 2.2 TCEB2 200085_s_at Hs.172772 transcription elongation factor B -6.8 -2.0 1.5 TFEB 50221_at Hs.23391 transcription factor EB -17.4 -1.7 TFEB 221866_at Hs.23391 transcription factor EB -3.5 TRIM8 221012_s_at Hs.54580 tripartite motif-containing 8 -3.2 -1.8 -1.6 -1.7 -1.9 UBN1 207253_s_at Hs.21479 ubinuclein 1 -26.2 -1.8 -1.8 ZNF216 210275_s_at Hs.406096 zinc finger protein 216 -2.4 ZNF435 219676_at Hs.288539 zinc finger protein 435 -3.0 -1.7

Unknown function Up-regulated (28) CECR5 218592_s_at Hs.26890 cat eye syndrome chromosome region, candidate 5 2.1 -1.5 1.6 -1.6 FLJ10996 219774_at Hs.98324 hypothetical protein FLJ10996 6.0 1.5 FLJ11088 218545_at Hs.406485 hypothetical protein FLJ11088 2.3 -2.3 1.9 -2.1 FLJ20373 218181_s_at Hs.6631 hypothetical protein FLJ20373 2.6 1.7 2.0 FLJ20449 220129_at Hs.130546 hypothetical protein FLJ20449 2.5 1.5 -2.1 FLJ20986 219558_at Hs.324507 hypothetical protein FLJ20986 3.6 2.3 1.8 2.4 FLJ20986 212297_at Hs.324507 hypothetical protein FLJ20986 6.3 FLJ22938 220193_at Hs.87016 hypothetical protein FLJ22938 5.1 1.9 FLJ23056 219427_at Hs.20914 hypothetical protein FLJ23056 2.4 2.2 FLJ23056 219427_at Hs.20914 hypothetical protein FLJ23056 2.4 FLJ23231 218810_at Hs.288300 hypothetical protein FLJ23231 3.1 1.6 1.6 2.5 KIAA0352 205256_at Hs.17262 KIAA0352 gene product 2.2 2.0 -1.7 -2.7 KIAA0980 207705_s_at Hs.227743 KIAA0980 protein 2.4 2.2 -1.7 LOC54103 213142_x_at Hs.12969 hypothetical protein LOC54103 2.4 1.6 2.1 LOC116150 215207_x_at Hs.289008 hypothetical protein, MGC:7199 2.9 1.6 -2.1 MGC12518 215239_x_at Hs.290768 similar to zinc finger protein 257 2.0 1.6 -1.6 NRIP3 219557_s_at Hs.32017 nuclear receptor interacting protein 3 3.3 1.9 2.2 1.5 NUPL1 204435_at Hs.406243 nucleoporin like 1 2.0 2.2 PDE4DIP 209700_x_at Hs.265848 phosphodiesterase 4D interacting protein 2.5 1.7 2.2 -1.5 PRO0971 219023_at Hs.152316 hypothetical protein PRO0971 2.0 1.9 2.2 RPEL1 213638_at Hs.191979 RPEL repeat containing 1 9.1 2.1 2TRPA1 208349_at Hs.137674 transient receptor potential cation channel 2.9 1.5 -2.1 --- 205708_s_at Hs.386010 transient receptor potential-related channel 7 homolog 4.6 1.9 --- 212012_at Hs.401975 clone IMAGE:4792124 2.1 1.9 -2.0 --- 212340_at Hs.82719 cDNA DKFZp586F1822 2.6 1.6 2.2 -1.5 --- 214349_at Hs.374989 cDNA: FLJ23438 fis 2.4 2.0 -3.5 --- 214657_s_at Hs.434021 137308 mRNA sequence 2.6 1.5 --- 215893_x_at Hs.326722 IMAGE:205688 2.5 1.7 -2.6 --- 216431_at Hs.306807 cDNA: FLJ21710 fis 2.1 2.3 --- 217578_at Hs.201420 FLJ20378 homolog 2.4 2.2

Down-regulated (28) BICD2 213154_s_at Hs.330988 coiled-coil protein BICD2 -8.3 -1.8 2.2 BRD1 204520_x_at Hs.127950 bromodomain containing 1 -2.0 -1.6 BTBD14A 212993_at Hs.23964 BTB (POZ) domain containing 14A -9.3 -1.8 -2.2

10 CGI-72 222133_s_at Hs.318725 CGI-72 protein -2.2 -1.5 C13orf10 218422_s_at Hs.39140 chromosome 13 open reading frame 10 -2.3 -1.6 C14orf159 218298_s_at Hs.285673 chromosome 14 open reading frame 159 -7.4 -2.3 -1.5 -1.9 DKFZp586I1420 213546_at Hs.112423 hypothetical protein DKFZp586I1420 -3.5 -1.5 EZI 214746_s_at Hs.112158 likely ortholog of mouse zinc finger protein EZI -2.6 -1.6 -2.2 -1.5 FLJ21047 201875_s_at Hs.14891 hypothetical protein FLJ21047 -3.6 -1.5 FLJ10055 203827_at Hs.9398 hypothetical protein FLJ10055 -13.1 -2.0 FLJ10055 213836_s_at Hs.9398 hypothetical protein FLJ10055 -3.5 FLJ20530 218905_at Hs.279521 hypothetical protein FLJ20530 -6.3 -1.8 FLJ21308 219033_at Hs.406232 hypothetical protein FLJ21308 -3.1 -1.6 -1.6 FLJ13386 219242_at Hs.300876 hypothetical protein FLJ13386 -54.6 -1.5 -2.3 -1.6 FLJ13386 222151_s_at Hs.300876 hypothetical protein FLJ13386 -3.8 GLIPR1 204221_x_at Hs.64639 GLI pathogenesis-related 1 (glioma) -5.4 -2.6 -2.0 GLIPR1 204222_s_at Hs.64639 GLI pathogenesis-related 1 (glioma) -60.1 ITM2B 217731_s_at Hs.239625 integral membrane protein 2B -4.4 -2.0 ITM2B 217732_s_at Hs.239625 integral membrane protein 2B -3.6 KIAA0146 203973_s_at Hs.76722 KIAA0146 protein -7.7 -1.9 -1.5 1.8 KIAA1109 212779_at Hs.6606 hypothetical protein KIAA1109 -4.6 -1.5 2.1 KIAA0779 213351_s_at Hs.362996 KIAA0779 protein -17.7 -2.3 KIAA0779 213349_at Hs.362996 KIAA0779 protein -2.9 -1.6 KIAA0471 203020_at Hs.242271 KIAA0471 gene product -2.2 -1.5 -1.8 -1.8 KIAA0876 212496_s_at Hs.301011 KIAA0876 protein -9.3 -2.4 -1.6 KIAA0876 212492_s_at Hs.301011 KIAA0876 protein -2.7 -1.8 KIAA0650 212569_at Hs.8118 KIAA0650 protein -8.0 -1.9 -1.8 KIAA0650 212579_at Hs.8118 KIAA0650 protein -9.2 KIAA0650 212577_at Hs.8118 KIAA0650 protein -7.8 -1.5 KIAA0290 213669_at Hs.96485 KIAA0290 protein -7.6 -2.6 LOC90410 210312_s_at Hs.4187 LOC90410: intraflagellar transport protein IFT20 -7.1 -1.5 -2.3 2.0 MGC31957 210484_s_at Hs.253829 hypothetical protein MGC31957 -6.2 1.7 -2.5 -1.8 MGC31957 210483_at Hs.253829 hypothetical protein MGC31957 -5.9 -1.6 MGC10986 218600_at Hs.50601 hypothetical protein MGC10986 -13.0 -2.3 --- 201861_s_at Hs.326159 NP_004726.1 homolog -2.5 1.8 -2.1 -2.2 --- 213224_s_at Hs.422407 cDNA: FLJ22071 fis, clone HEP11691. -3.5 -1.9 --- 214405_at Hs.12533 23705 mRNA sequence -5.1 -1.8

A. phagocytophilum only Up-regulated (14) ADA 204639_at Hs.1217 adenosine deaminase -1.1 1.6 1.9 2.1 ADAM17 205745_x_at Hs.380136 a disintegrin and metalloproteinase domain 17 1.4 1.5 2.8 BID 204493_at Hs.172894 BH3-interacting domain death agonist -1.4 2.1 BID 211725_s_at Hs.172894 BH3-interacting domain death agonist -1.0 2.6 C1orf16 201794_s_at Hs.15087 chromosome 1 open reading frame 16 -1.3 2.2 CCL19 210072_at Hs.50002 chemokine (C-C motif) ligand 19 1.2 1.5 3.8 CCR1 205098_at Hs.301921 chemokine (C-C motif) receptor 1 1.5 2.5 CCR1 205099_s_at Hs.301921 chemokine (C-C motif) receptor 1 1.5 1.9 CHST7 206756_at Hs.138155 carbohydrate sulfotransferase 7 1.4 3.3 LTBR 203005_at Hs.1116 lymphotoxin beta receptor 1.4 2.0 1.7 PDE4B 211302_s_at Hs.188 phosphodiesterase 4B, cAMP-specific -1.7 1.7 2.1 PLAGL2 202924_s_at Hs.154104 pleiomorphic adenoma gene-like 2 1.4 -2.0 2.0

11 SERPINB2 204614_at Hs.75716 serine (or cysteine) proteinase inhibitor 1.3 3.6 SLC7A7 204588_s_at Hs.194693 cationic amino acid transporter 1.3 1.8 1.9 3.2 TPM4 209344_at Hs.250641 tropomyosin 4 -1.4 2.0 1.7 -1.9 WBP2 209117_at Hs.231840 WW domain binding protein 2 -1.3 2.0 1.9

Down-regulated (17) BFAR 218056_at Hs.168159 bifunctional apoptosis regulator 1.2 -2.3 BMP2K 214716_at Hs.20137 BMP2 inducible kinase 1.3 -2.1 C1QBP 208910_s_at Hs.78614 C component 1, q subcomponent binding protein 1.0 -2.3 -1.8 -1.8 CA4 206209_s_at Hs.89485 carbonic anhydrase IV -1.3 -2.0 -1.7 DKFZP586M1523 212055_at Hs.22981 DKFZP586M1523 protein 1.1 -2.0 -1.6 DLEU2 216870_x_at Hs.43628 deleted in lymphocytic leukemia, 2 1.1 -2.0 -1.7 -3.2 GTF2H2 221540_x_at Hs.191356 general transcription factor IIH, polypeptide 2 1.3 -1.7 -4.5 HNRPDL 209067_s_at Hs.372673 heterogeneous nuclear ribonucleoprotein D-like -1.3 -2.3 MCM4 222036_s_at Hs.154443 minichromosome maintenance deficient 4 1.3 -2.1 -2.3 MPZL1 210087_s_at Hs.287832 myelin protein zero-like 1 1.1 -2.2 PAM 212958_x_at Hs.83920 peptidylglycine alpha-amidating monooxygenase 1.4 -2.6 PPP2R5C 214083_at Hs.171734 protein phosphatase 2, regulatory subunit B -1.1 -2.0 2.3 PRKAB1 201834_at Hs.6061 protein kinase, AMP-activated, beta 1 1.2 -2.2 RPL27A 212044_s_at Hs.76064 ribosomal protein L27a -1.0 -2.2 RPL34 200026_at Hs.250895 ribosomal protein L34 -1.3 -2.0 SSNA1 210378_s_at Hs.18528 Sjogren's syndrome nuclear autoantigen 1 1.2 -1.5 -2.1 --- 214850_at --- -1.2 -2.5

S. aureus only Metabolism and vesicle trafficking Up-regulated (146) ABCC1 202804_at Hs.89433 ATP-binding cassette 2.0 ABCG4 207593_at Hs.126378 ATP-binding cassette 2.6 ADFP 209122_at Hs.3416 adipose differentiation-related protein 8.4 ADH5 208848_at Hs.78989 alcohol dehydrogenase 5 2.5 AKR1C1 204151_x_at Hs.431175 aldo-keto reductase family 1, member C1 2.0 AKR1D1 207102_at Hs.201667 aldo-keto reductase family 1, member D1 2.2 AK3 204348_s_at Hs.274691 adenylate kinase 3 2.6 1.7 ALDH7A1 208951_at Hs.74294 aldehyde dehydrogenase 7 family, member A1 2.0 ALG1 210169_at Hs.129883 asparagine-linked glycosylation 1 homolog 2.1 ARTS-1 214034_at Hs.247043 type 1 TNF receptor shedding aminopeptidase regulator 2.3 -2.3 -2.1 ATP6V0C 36994_at Hs.389107 ATPase, H+ transporting, lysosomal 2.3 ATP6V1C1 202872_at Hs.86905 ATPase, H+ transporting, lysosomal 3.2 ATP6V1F 201527_at Hs.78089 ATPase, H+ transporting, lysosomal 7.0 B3GNT4 221240_s_at Hs.191450 UDP-GlcNAc:-N-acetylglucosaminyltransferase 4 2.1 -1.6 CACNA1A 214933_at Hs.96253 calcium channel, voltage-dependent 2.4 CAST 207467_x_at Hs.359682 calpastatin 2.2 CAS1 219342_at Hs.128003 O-acetyltransferase 2.2 CA1 205949_at Hs.23118 carbonic anhydrase I 2.7 CHPF 202175_at Hs.7718 chondroitin polymerizing factor 2.2 CLCN5 206704_at Hs.89872 chloride channel 5 2.5 CLTA 216296_at Hs.104143 clathrin, light polypeptide (Lca) 2.3 COX6A2 206353_at Hs.250760 cytochrome c oxidase subunit 2.2

12 CSPG5 39966_at Hs.45127 chondroitin sulfate proteoglycan 5 2.6 CYLC2 207780_at Hs.3232 cylicin 2.6 CYP1A2 207608_x_at Hs.1361 cytochrome P450, family 1, subfamily A, polypeptide 2 2.5 CYP2C9 214421_x_at Hs.167529 cytochrome P450, family 2, subfamily C, polypeptide 9 2.2 CYP2C9 216025_x_at Hs.167529 cytochrome P450, family 2, subfamily C, polypeptide 9 2.4 CYP7B1 207386_at Hs.144877 cytochrome P450, family 7, subfamily B, polypeptide 1 2.3 DCT 205338_s_at Hs.301865 dopachrome tautomerase 2.1 DHFR 202534_x_at Hs.83765 dihydrofolate reductase 2.8 DNAJB4 203810_at Hs.41693 DnaJ (Hsp40) homolog, subfamily B, member 4 2.6 DNAJB9 202842_s_at Hs.6790 DnaJ (Hsp40) homolog, subfamily B, member 9 3.1 1.6 DNAJC4 213919_at Hs.172847 DnaJ (Hsp40) homolog, subfamily C, member 4 2.2 DNAJC9 213088_s_at Hs.44131 DnaJ (Hsp40) homolog, subfamily C, member 9 2.2 DPAGT1 209509_s_at Hs.26433 dolichyl-phosphate GlcNAc phosphotransferase 1 2.1 DPP6 207789_s_at Hs.34074 dipeptidylpeptidase 6 2.3 EEF1E1 213907_at Hs.433779 eukaryotic translation elongation factor 1 epsilon 1 2.3 EIF2AK3 218696_at Hs.102506 eukaryotic translation initiation factor 2-alpha kinase 3 5.6 EIF4A1 201530_x_at Hs.129673 eukaryotic translation initiation factor 4A, isoform 1 3.1 EIF4A1 211787_s_at Hs.129673 eukaryotic translation initiation factor 4A, isoform 1 2.6 EIF4E 201437_s_at Hs.79306 eukaryotic translation initiation factor 4E 2.9 1.7 EIF4E 201435_s_at Hs.79306 eukaryotic translation initiation factor 4E 1.7 1.9 1.6 EXTL2 209537_at Hs.61152 exostoses (multiple)-like 2 2.3 FACL5 218322_s_at Hs.11638 fatty-acid-Coenzyme A ligase, long-chain 5 2.6 FACL6 211207_s_at Hs.14945 fatty-acid-Coenzyme A ligase, long-chain 6 2.2 1.5 FETUB 214417_s_at Hs.81073 fetuin B 2.2 -4.4 FMO4 206263_at Hs.2664 flavin containing monooxygenase 4 2.4 FOLH1 217487_x_at Hs.1915 folate hydrolase 1 2.4 F7 207300_s_at Hs.36989 coagulation factor VII 2.2 F13B 207810_at Hs.68601 coagulation factor XIII, B polypeptide 3.1 GABARAPL2 209046_s_at Hs.6518 GABA(A) receptor-associated protein-like 2 2.1 GALNACT-2 218871_x_at Hs.180758 chondroitin sulfate GalNAcT-2 2.2 GATM 216733_s_at Hs.75335 glycine amidinotransferase 2.2 GBA 209093_s_at Hs.282997 glucosidase, beta; acid (includes glucosylceramidase) 2.3 GBE1 203282_at Hs.1691 glucan (1,4-alpha-), branching enzyme 1 5.5 1.6 GGA1 50277_at Hs.238296 golgi-associated ARF binding protein 1 2.6 GGA1 45572_s_at Hs.238296 golgi-associated ARF binding protein 1 2.8 GGH 203560_at Hs.78619 gamma-glutamyl hydrolase 2.1 GGT1 207131_x_at Hs.446503 gamma-glutamyltransferase 1 2.1 GGT1 208284_x_at Hs.446503 gamma-glutamyltransferase 1 2.1 GGT1 209919_x_at Hs.352119 gamma-glutamyltransferase 1 2.3 1.6 GGT1 211417_x_at Hs.352120 gamma-glutamyltransferase 1 2.2 GGT2 215603_x_at Hs.289098 gamma-glutamyltransferase 2 2.5 GLA 214430_at Hs.69089 galactosidase, alpha 7.3 GLRA1 207972_at Hs.121490 glycine receptor, alpha 1 2.7 GLYAT 206930_at Hs.18508 glycine-N-acyltransferase 2.1 GOLGIN-67 213650_at Hs.182982 golgin-67 2.1 GRIN2B 210412_at Hs.1198 glutamate receptor, ionotropic, NMDA 2B 2.3 GSTA1 215766_at Hs.446309 GST A1 2.0 GSTTLp28 201470_at Hs.11465 GST like; glutathione transferase omega 4.9 HGNT-IV-H 207447_s_at Hs.227473 UDP-GlcNAc:N-acetylglucosaminyltransferase hom. 2.6

13 HIG2 218507_at Hs.61762 hypoxia-inducible protein 2 4.7 HPS1 203309_s_at Hs.83951 Hermansky-Pudlak syndrome 1 2.2 HPS5 204544_at Hs.29205 HPS5: Hermansky-Pudlak syndrome 5 3.3 HSD11B1 205404_at Hs.275215 hydroxysteroid (11-beta) dehydrogenase 1 2.2 HSPA9B 200691_s_at Hs.3069 heat shock 70kDa protein 9B (mortalin-2) 2.1 IREB2 214666_x_at Hs.295789 iron-responsive element binding protein 2 4.0 JTV1 209972_s_at Hs.301613 JTV1 gene 2.2 KCNJ5 211304_x_at Hs.193044 potassium inwardly-rectifying channel 2.8 KIF2C 211519_s_at Hs.69360 kinesin family member 2C 2.1 KIF14 206364_at Hs.3104 kinesin family member 14 2.5 -1.8 KMO 205306_x_at Hs.107318 kynurenine 3-monooxygenase 2.9 1.7 KPNA5 206241_at Hs.182971 karyopherin alpha 5 (importin alpha 6) 2.2 LCT 206945_at Hs.2251 lactase 2.8 -2.4 LDHA 200650_s_at Hs.2795 lactate dehydrogenase A 5.4 LMO7 202674_s_at Hs.5978 LIM domain only 7 2.7 LOX 215446_s_at Hs.102267 lysyl oxidase 2.4 ME1 204058_at Hs.14732 malic enzyme 1, NADP(+)-dependent, cytosolic 2.4 -2.1 MLPH 218211_s_at Hs.297405 melanophilin 3.6 MMP14 160020_at Hs.2399 matrix metalloproteinase 14 (membrane-inserted) 2.1 MRPL15 218027_at Hs.18349 mitochondrial ribosomal protein L15 2.1 MRPL44 218202_x_at Hs.203559 mitochondrial ribosomal protein L44 2.0 -1.5 MTAP 211364_at Hs.152817 methylthioadenosine phosphorylase 2.1 MTA1 202247_s_at Hs.101448 metastasis associated 1 2.1 MUT 202959_at Hs.155212 methylmalonyl Coenzyme A mutase 2.6 NDUFC2 206936_x_at Hs.193313 NADH dehydrogenase (ubiquinone) 1, subcomplex 2.5 NEDD4 213012_at Hs.1565 neural precursor cell expressed, dev. down-regulated 4 2.2 NOX4 219773_at Hs.93847 NADPH oxidase 4 2.1 NPC1 202679_at Hs.76918 Niemann-Pick disease, type C1 3.8 Nup37 218622_at Hs.5152 nucleoporin Nup37 2.1 -2.3 OAZIN 201772_at Hs.223014 ornithine decarboxylase antizyme inhibitor 2.3 PDE4D 210837_s_at Hs.172081 phosphodiesterase 4D, cAMP-specific 2.6 PDE4D 210836_x_at Hs.172081 phosphodiesterase 4D, cAMP-specific 2.2 -2.1 PIN4 204572_s_at Hs.11774 peptidyl-prolyl cis/trans isomerase NIMA-interacting, 4 2.2 PIN4 214225_at Hs.11774 peptidyl-prolyl cis/trans isomerase NIMA-interacting, 4 2.4 PLA2G7 206214_at Hs.93304 phospholipase A2, group VII 3.1 PLSCR4 218901_at Hs.182538 phospholipid scramblase 4 2.4 -3.5 PMP2 206826_at Hs.2868 peripheral myelin protein 2 2.5 PON1 206344_at Hs.1898 paraoxonase 1 3.2 PPAT 209433_s_at Hs.311 phosphoribosyl pyrophosphate amidotransferase 2.5 PP591 205661_s_at Hs.118666 FAD-synthetase 2.4 PSME4 212220_at Hs.112396 proteasome (prosome, macropain) activator subunit 4 2.2 -1.7 -2.0 PTGES 210367_s_at Hs.146688 prostaglandin E synthase 2.4 PYCS 217791_s_at Hs.114366 pyrroline-5-carboxylate synthetase 3.4 P4HA1 207543_s_at Hs.76768 proline 4-hydroxylase, alpha polypeptide I 3.0 P4HB 200656_s_at Hs.410578 proline 4-hydroxylase, beta polypeptide 2.9 RABEX5 218310_at Hs.187660 putative Rab5 GDP/GTP exchange factor homologue 3.5 RAB21 203885_at Hs.184627 RAB21, member RAS oncogene family 2.3 RBSK 57540_at Hs.11916 ribokinase 2.4 -1.6 -2.1 -1.7 RPH3AL 221614_s_at Hs.198551 rabphilin 3A-like (without C2 domains) 2.5

14 RPP38 215743_at Hs.94986 ribonuclease P (38kD) 2.8 RPS14 214245_at Hs.431584 ribosomal protein S14 2.1 1.7 RYR3 206306_at Hs.9349 ryanodine receptor 3 3.1 SAT 203455_s_at Hs.28491 spermidine/spermine N1-acetyltransferase 2.1 -1.5 -2.6 SCD4 220232_at Hs.379191 stearoyl-CoA desaturase 4 3.4 -3.6 -1.6 -1.6 SCN11A 220791_x_at Hs.186877 sodium channel, voltage-gated, type XI 2.1 1.6 SERPINB13 217272_s_at Hs.241407 serine (or cysteine) proteinase inhibitor 2.5 SLCO4C1 207596_at Hs.127648 organic anion transporter family, member 4C1 2.2 SLC1A4 212811_x_at Hs.286049 glutamate/neutral amino acid transporter 2.2 SLC1A4 209610_s_at Hs.323878 glutamate/neutral amino acid transporter 1.1 -1.8 SLC1A7 210923_at Hs.104637 glutamate transporter 2.1 SLC3A2 200924_s_at Hs.79748 activators of dibasic and neutral amino acid transport 3.8 SLC12A2 204404_at Hs.110736 sodium/potassium/chloride transporters 2.8 SLC15A1 211349_at Hs.2217 oligopeptide transporter 2.0 SLC16A7 210807_s_at Hs.132183 monocarboxylic acid transporters 2.5 SLC17A6 220551_at Hs.242821 sodium-dependent inorganic phosphate cotransporter 2.7 SLC19A3 220736_at Hs.306236 solute carrier family 19, member 3 2.2 SLC21A3 207308_at Hs.46440 organic anion transporter 2.2 SLC25A13 203775_at Hs.9599 citrin 4.9 1.9 SLC25A16 209910_at Hs.380359 mitochondrial carrier; Graves disease autoantigen 2.2 SLC25A16 210686_x_at Hs.380359 mitochondrial carrier; Graves disease autoantigen 3.0 SLC26A10 214951_at Hs.159481 solute carrier family 26, member 10 2.9 SNX4 212652_s_at Hs.267812 sorting nexin 4 2.3 SPS 208939_at Hs.124027 selenophosphate synthetase 2.4 SPTLC2 216203_at Hs.59403 serine palmitoyltransferase, long chain base subunit 2 2.3 -2.1 SUI1 202021_x_at Hs.150580 putative translation initiation factor 2.2 SUI1 212130_x_at Hs.150580 putative translation initiation factor 2.5 SUI1 212227_x_at Hs.150580 putative translation initiation factor 2.5 SV2C 216086_at Hs.225974 synaptic vesicle protein 2C 2.4 -2.2 SYNJ2 212828_at Hs.61289 synaptojanin 2 3.1 1.6 SYN2 210247_at Hs.6439 synapsin II 2.4 TLL1 206415_at Hs.129700 tolloid-like 1 2.8 TOM1L1 204485_s_at Hs.153504 target of myb1-like 1 (chicken) 2.5 TPI1 200822_x_at Hs.83848 triosephosphate isomerase 1 3.6 TPI1 213011_s_at Hs.83848 triosephosphate isomerase 1 2.7 TPMT 203672_x_at Hs.381154 thiopurine S-methyltransferase 3.2 -2.5 -1.5 TRPC1 205803_s_at Hs.250687 transient receptor potential cation channel 2.7 TXNL2 214205_x_at Hs.42644 thioredoxin-like 2 3.0 -10.9 -2.4 UGT1A8 221304_at Hs.278741 UDP glycosyltransferase 1 family, polypeptide A8 2.4 USP46 203870_at Hs.109268 ubiquitin specific protease 46 2.4

Down-regulated (234) ABHD3 213017_at Hs.13377 abhydrolase domain containing 3 -5.0 ACAA1 214274_s_at Hs.166160 acetyl-Coenzyme A acyltransferase 1 -2.7 ACADVL 200710_at Hs.82208 acyl-Coenzyme A dehydrogenase, very long chain -2.5 ACLY 201128_s_at Hs.174140 ATP citrate lyase -2.0 ACLY 201127_s_at Hs.174140 ATP citrate lyase -1.2 -1.7 AHCYL1 200848_at Hs.4113 S-adenosylhomocysteine hydrolase-like 1 -4.1 AIM1 212543_at Hs.161002 absent in melanoma 1 -2.1

15 ALDH9A1 201612_at Hs.2533 aldehyde dehydrogenase 9 family, member A1 -4.2 ACOX1 213501_at Hs.379991 acyl-Coenzyme A oxidase 1, palmitoyl -3.7 ACOX1 209600_s_at Hs.379991 acyl-Coenzyme A oxidase 1, palmitoyl -2.4 ADPRTL1 202239_at Hs.77225 ADP-ribosyltransferase-like 1 -2.1 ALOX5 214366_s_at Hs.89499 arachidonate 5-lipoxygenase -7.7 ALOX5 204446_s_at Hs.89499 arachidonate 5-lipoxygenase -7.1 ALOX5 204445_s_at Hs.89499 arachidonate 5-lipoxygenase -6.4 ALOX5AP 204174_at Hs.100194 arachidonate 5-lipoxygenase-activating protein -2.0 AMD1 201196_s_at Hs.262476 S-adenosylmethionine decarboxylase 1 -5.9 -1.6 ANPEP 202888_s_at Hs.1239 alanyl (membrane) aminopeptidase -4.8 AP2M1 200613_at Hs.152936 adaptor-related protein complex 2, mu 1 subunit -7.4 ARCN1 201176_s_at Hs.33642 archain 1 -6.8 3.3 ARPP-19 221483_s_at Hs.7351 cyclic AMP phosphoprotein, 19 kD -2.3 ATP2A3 213036_x_at Hs.5541 ATPase, Ca++ transporting, ubiquitous -7.1 ATP2B4 212136_at Hs.343522 ATPase, Ca++ transporting, plasma membrane 4 -3.2 1.8 ATP5A1 211755_s_at Hs.405985 ATP synthase, H+ transporting, mitochondrial -3.1 ATP5F1 217801_at Hs.81634 ATP synthase, H+ transporting, mitochondrial -6.0 ATP5E 208746_x_at Hs.177530 ATP synthase, H+ transporting, mitochondrial -3.9 ATP5H 210453_x_at Hs.49018 ATP synthase, H+ transporting, mitochondrial -2.4 ATP5I 207573_x_at Hs.85539 ATP synthase, H+ transporting, mitochondrial -2.3 ATP5J2 213738_s_at Hs.235557 ATP synthase, H+ transporting, mitochondrial -16.5 ATP5L 201444_s_at Hs.107476 ATP synthase, H+ transporting, mitochondrial -3.5 ATP5L 201443_s_at Hs.107476 ATP synthase, H+ transporting, mitochondrial -2.8 ATP5L 210149_s_at Hs.107476 ATP synthase, H+ transporting, mitochondrial -2.7 ATP5O 209492_x_at Hs.433960 ATP synthase, H+ transporting, mitochondrial -25.3 ATP6IP2 202961_s_at Hs.183434 ATPase, H+ transporting, lysosomal interacting prot. 2 -2.6 ATP6IP2 201972_at Hs.183434 ATPase, H+ transporting, lysosomal interacting prot. 2 -2.5 ATP6V1A1 201971_s_at Hs.281866 ATPase, H+ transporting, lysosomal -2.1 ATP6V1A1 200818_at Hs.281866 ATPase, H+ transporting, lysosomal -10.5 1.6 3.6 BIG1 202956_at Hs.94631 BFA-inhibited guanine nucleotide-exchange protein 1 -4.0 BIN2 219191_s_at Hs.14770 bridging integrator 2; endocytosis -18.4 -1.8 CAT 211922_s_at Hs.395771 catalase -44.6 CAT 201432_at Hs.395771 catalase -9.8 CDA 205627_at Hs.72924 cytidine deaminase -36.5 -1.6 CDIPT 201253_s_at Hs.121549 CDP-diacylglycerol--inositol 3-phosphatidyltransferase -7.0 ChGn 219049_at Hs.11260 chondroitin beta1,4 N-acetylgalactosaminyltransferase -5.0 2.1 CHPT1 221675_s_at Hs.171889 choline phosphotransferase 1 -2.7 CHST6 221059_s_at Hs.157439 carbohydrate sulfotransferase 6 -10.8 -1.8 CHSY1 203044_at Hs.110488 carbohydrate (chondroitin) synthase 1 -2.5 CLC 206207_at Hs.889 Charot-Leyden crystal protein -12.2 -1.9 CLIC1 208659_at Hs.414565 chloride intracellular channel 1 -2.8 COPS3 202078_at Hs.6076 COP9 constitutive photomorphogenic hom. subunit 3 -3.8 -2.0 COX5B 211025_x_at Hs.1342 cytochrome c oxidase subunit Vb -6.9 COX5B 213735_s_at Hs.1342 cytochrome c oxidase subunit Vb -3.0 COX5B 202343_x_at Hs.1342 cytochrome c oxidase subunit Vb -6.3 -1.7 COX6B 201441_at Hs.431668 cytochrome c oxidase subunit VIb -4.4 COX7B 202110_at Hs.432170 cytochrome c oxidase subunit VIIb -2.9 CPNE3 202119_s_at Hs.14158 copine III -3.8 CPT1B 204193_at Hs.154886 carnitine palmitoyltransferase 1B (muscle) -4.1

16 CSTA 204971_at Hs.412999 cystatin A (stefin A) -6.1 CTBS 218924_s_at Hs.135578 chitobiase, di-N-acetyl- -3.1 CTBS 218923_at Hs.135578 chitobiase, di-N-acetyl- -2.3 CTBP1 203392_s_at Hs.343926 C-terminal binding protein 1 -2.3 CTBP1 212863_x_at Hs.343926 C-terminal binding protein 1 -2.2 CTBP1 213980_s_at Hs.343926 C-terminal binding protein 1 -65.9 2.3 CYP4F3 206515_at Hs.106242 cytochrome P450, family 4, subfamily F, polypeptide 3 -2.8 C4ST 219634_at Hs.64001 chondroitin 4-sulfotransferase -2.7 DAZAP2 212595_s_at Hs.75416 DAZ associated protein 2 -2.7 DECR1 202447_at Hs.81548 2,4-dienoyl CoA reductase 1, mitochondrial -3.4 DEGS 209250_at Hs.185973 degenerative spermatocyte homolog, lipid desaturase -2.0 DNAJA1 200880_at Hs.94 DnaJ (Hsp40) homolog, subfamily A, member 1 -2.5 DNAJB6 208811_s_at Hs.181195 DnaJ (Hsp40) homolog, subfamily B, member 6 -6.0 DNAJB6 208810_at Hs.181195 DnaJ (Hsp40) homolog, subfamily B, member 6 -4.0 DNAJB6 209015_s_at Hs.181195 DnaJ (Hsp40) homolog, subfamily B, member 6 -25.6 2.4 DPM1 202673_at Hs.5085 dolichyl-phosphate mannosyltransferase polypeptide 1 -2.2 DPP8 220939_s_at Hs.44033 dipeptidylpeptidase 8 -2.3 EEF1D 203113_s_at Hs.334798 eukaryotic translation elongation factor 1 delta -2.3 EEF1D 214394_x_at Hs.334798 eukaryotic translation elongation factor 1 delta -2.3 EIF4A2 200912_s_at Hs.173912 eukaryotic translation initiation factor 4A, isoform 2 -2.0 EIF4EBP2 208770_s_at Hs.278712 eukaryotic translation initia. factor 4E binding protein 2 -2.8 EIF4EL3 213571_s_at Hs.19122 eukaryotic translation initiation factor 4E-like 3 -35.3 -1.5 EIF3S5 200023_s_at Hs.7811 eukaryotic translation initiat. factor 3, subunit 5 epsilon -2.0 EIF3S6IP 217719_at Hs.119503 eukaryotic translation initiation factor 3, subunit 6 -2.4 -1.7 EIF3S7 200005_at Hs.55682 eukaryotic translation initiation factor 3, subunit 7 zeta -2.6 EIF4G2 200004_at Hs.183684 eukaryotic translation initiation factor 4 gamma, 2 -4.2 ELOVL1 57163_at Hs.25597 elongation of very long chain fatty acids-like 1 -3.3 ENSA 202596_at Hs.111680 endosulfine alpha -6.0 ENTPD1 209473_at Hs.205353 CD39 -2.9 FBXW2 209630_s_at Hs.355780 F-box and WD-40 domain protein 2 -2.7 FDFT1 208647_at Hs.48876 farnesyl-diphosphate farnesyltransferase 1 -2.0 GCC2 202832_at Hs.278671 GRIP and coiled-coil domain-containing 2 -2.4 UDP-N-acetyl-α-D-galactosamine:polypeptide GALNT7 218313_s_at Hs.246315 GalNAc-T7 -2.6 GMPR2 217990_at Hs.234546 guanosine monophosphate reductase 2 -8.3 3.1 GOLPH3 217803_at Hs.18271 golgi phosphoprotein 3 (coat-protein) -2.4 GPX3 214091_s_at Hs.386793 glutathione peroxidase 3 (plasma) -2.4 -1.5 GRP58 208612_at Hs.13751 glucose regulated protein, 58 kDa -3.7 2.6 G6PD 202275_at Hs.80206 glucose-6-phosphate dehydrogenase -12.3 HARSL 209252_at Hs.278507 histidyl-tRNA synthetase-like -2.5 HDAC1 201209_at Hs.88556 histone deacetylase 1 -8.2 2.4 HERPUD1 217168_s_at Hs.146393 ubiquitin-like domain member -3.8 HIP2 202347_s_at Hs.155485 huntingtin interacting protein 2 -4.0 HMGCR 202539_s_at Hs.11899 3-hydroxy-3-methylglutaryl-Coenzyme A reductase -2.5 HMGCR 202540_s_at Hs.11899 3-hydroxy-3-methylglutaryl-Coenzyme A reductase -2.2 HRB2 214085_x_at Hs.154762 HIV-1 rev binding protein 2 -9.8 HSPA6 213418_at Hs.3268 heat shock 70kDa protein 6 (HSP70B') -5.2 HSPA6 117_at Hs.3268 heat shock 70kDa protein 6 (HSP70B') -2.8 HSPBAP1 219284_at Hs.29169 HSPB (heat shock 27kDa) associated protein 1 -4.0 HSPC051 218190_s_at Hs.284292 ubiquinol-cytochrome c reductase complex (7.2 kD) -8.9

17 KARS 200840_at Hs.3100 lysyl-tRNA synthetase -2.3 KIF5B 201991_s_at Hs.149436 kinesin family member 5B -3.5 KPNA2 201088_at Hs.159557 karyopherin alpha 2 (RAG cohort 1, importin alpha 1) -8.9 KPNB1 213574_s_at Hs.180446 karyopherin (importin) beta 1 -2.9 KPNB1 208975_s_at Hs.180446 karyopherin (importin) beta 1 -4.3 KPNB1 213507_s_at Hs.180446 karyopherin (importin) beta 1 -4.4 KPNB1 208974_x_at Hs.180446 karyopherin (importin) beta 1 -5.7 KPNB1 213803_at Hs.180446 karyopherin (importin) beta 1 -1.5 -1.5 LIN7A 206440_at Hs.416087 lin-7 homolog A (C. elegans) -8.3 LTA4H 208771_s_at Hs.81118 leukotriene A4 hydrolase -7.4 -1.6 LYPLA1 212449_s_at Hs.12540 lysophospholipase I -2.1 LYSAL1 204076_at Hs.201377 lysosomal apyrase-like 1 -2.6 MANBA 203778_at Hs.115945 mannosidase, beta A, lysosomal -2.3 MAN2A2 202032_s_at Hs.295605 mannosidase, alpha, class 2A, member 2 -3.6 -1.7 MAT2B 217993_s_at Hs.54642 methionine adenosyltransferase II, beta -2.7 ME2 209397_at Hs.75342 malic enzyme 2, NAD(+)-dependent, mitochondrial -8.2 -1.6 ME2 210153_s_at Hs.75342 malic enzyme 2, NAD(+)-dependent, mitochondrial -2.4 MFN1 207098_s_at Hs.197877 mitofusin 1 -4.2 MGAM 206522_at Hs.122785 maltase-glucoamylase (alpha-glucosidase) -30.7 MGAT2 203102_s_at Hs.172195 mannosyl-N-acetylglucosaminyltransferase -3.2 1.6 2.4 MGEA5 200899_s_at Hs.5734 meningioma expressed antigen 5 (hyaluronidase) -8.6 MGEA5 200898_s_at Hs.5734 meningioma expressed antigen 5 (hyaluronidase) -8.6 2.2 MIR 221824_s_at Hs.288156 c-mir, cellular modulator of immune recognition -6.3 -1.6 MMP25 207890_s_at Hs.198265 matrix metalloproteinase 25 -9.9 -1.8 MSCP 218978_s_at Hs.283716 mitochondrial solute carrier protein -4.9 MSCP 218136_s_at Hs.283716 mitochondrial solute carrier protein -3.0 NAGK 218231_at Hs.7036 N-acetylglucosamine kinase -2.5 NDUFA2 209224_s_at Hs.163867 ubiquinone 1 alpha subcomplex, 2, 8kDa -2.6 -1.6 NDUFA3 218563_at Hs.198269 ubiquinone 1 alpha subcomplex, 3, 9kDa -5.5 NDUFB1 206790_s_at Hs.183435 ubiquinone 1 beta subcomplex, 1, 7kDa -6.6 NDUFB4 218226_s_at Hs.227750 ubiquinone 1 beta subcomplex, 4, 15kDa -2.5 NKTR 202379_s_at Hs.432885 natural killer-tumor recognition sequence -6.8 NPEPL1 221499_s_at Hs.71746 aminopeptidase-like 1 -6.9 NPEPL1 221500_s_at Hs.71746 aminopeptidase-like 1 -3.1 NPEPPS 201455_s_at Hs.293007 aminopeptidase puromycin sensitive -2.3 NPL 221210_s_at Hs.23756 N-acetylneuraminate pyruvate lyase -3.1 NQO2 203814_s_at Hs.73956 NAD(P)H dehydrogenase, quinone 2 -6.4 NRD1 208709_s_at Hs.4099 nardilysin (N-arginine dibasic convertase) -2.5 NUDEL 208093_s_at Hs.3850 LIS1-interacting protein NUDEL; endooligopeptidase A -5.4 NUP50 213682_at Hs.367697 nucleoporin 50kDa -3.7 NUP50 218294_s_at Hs.367697 nucleoporin 50kDa -2.5 NUP214 202155_s_at Hs.170285 nucleoporin 214kDa -2.3 -1.8 NUP153 202097_at Hs.211608 nucleoporin 153kDa -2.2 OAZ1 200077_s_at Hs.281960 ornithine decarboxylase antizyme 1 -3.2 OAZ1 215952_s_at Hs.405050 ornithine decarboxylase antizyme 1 -6.4 OAZ2 201365_at Hs.74563 ornithine decarboxylase antizyme 2 -2.6 OGT 212307_s_at Hs.100293 O-linked GlcNAc transferase -7.2 OGT 209240_at Hs.100293 O-linked GlcNAc transferase -2.9 OSBPL2 209222_s_at Hs.15519 oxysterol binding protein-like 2 -11.7 2.0

18 OSBPL8 212582_at Hs.109694 oxysterol binding protein-like 8 -2.5 OSBPL8 212585_at Hs.109694 oxysterol binding protein-like 8 -2.8 OSBPL9 218047_at Hs.21938 oxysterol binding protein-like 9 -4.0 OSBPL11 218304_s_at Hs.61260 oxysterol binding protein-like 11 -3.4 OTUB1 201245_s_at Hs.108504 OTU domain, ubiquitin aldehyde binding 1 -3.7 2.4 PADI2 209791_at Hs.33455 peptidyl arginine deiminase, type II -2.6 PANK2 218809_at Hs.286212 pantothenate kinase 2 -3.1 PAPSS1 209043_at Hs.3833 3'-phosphoadenosine 5'-phosphosulfate synthase 1 -11.6 PGCP 208454_s_at Hs.197335 plasma glutamate carboxypeptidase -14.1 -1.5 PGCP 203501_at Hs.197335 plasma glutamate carboxypeptidase -3.4 -1.9 PGD 201118_at Hs.392837 phosphogluconate dehydrogenase -6.8 PGLS 218387_s_at Hs.100071 6-phosphogluconolactonase -3.7 -1.8 PPIB 200967_at Hs.394389 peptidylprolyl isomerase B (cyclophilin B) -3.0 P44S10 202753_at Hs.23488 proteasome regulatory particle subunit p44S10 -2.7 PPT1 200975_at Hs.3873 palmitoyl-protein thioesterase 1 -2.0 PSMA3 201532_at Hs.346918 proteasome subunit, alpha type, 3 -4.2 PSMB1 200876_s_at Hs.407981 proteasome subunit, beta type, 1 -5.5 PSMB3 201400_at Hs.82793 proteasome subunit, beta type, 3 -4.8 PSMB4 202244_at Hs.89545 proteasome subunit, beta type, 4 -3.1 PSMB4 202243_s_at Hs.89545 proteasome subunit, beta type, 4 -3.5 3.9 PSMB7 200786_at Hs.433434 proteasome subunit, beta type, 7 -5.0 PSMB8 209040_s_at Hs.180062 proteasome subunit, beta type, 8 -23.1 3.8 PSMB9 204279_at Hs.381081 proteasome subunit, beta type, 9 -5.4 PSMB10 202659_at Hs.9661 proteasome subunit, beta type, 10 -15.0 -1.6 PSMD4 210460_s_at Hs.148495 proteasome 26S subunit, non-ATPase, 4 -9.6 2.7 2.6 PSMD13 201232_s_at Hs.279554 proteasome 26S subunit, non-ATPase, 13 -2.4 PSME1 200814_at Hs.75348 proteasome activator subunit 1 -4.3 PSME3 209852_x_at Hs.152978 proteasome activator subunit 3 -2.2 PTTG1IP 200677_at Hs.111126 pituitary tumor-transforming 1 interacting protein -2.9 PYGL 202990_at Hs.771 phosphorylase, glycogen -6.7 -1.8 RER1 202297_s_at Hs.40500 similar to S. cerevisiae RER1 -2.5 RetSDR2 217989_at Hs.12150 retinal short-chain dehydrogenase/reductase 2 -17.8 RetSDR4 210788_s_at Hs.109201 retinal short-chain dehydrogenase/reductase 4 -4.1 RPN1 201011_at Hs.2280 ribophorin I -4.4 RPL11 200010_at Hs.388664 ribosomal protein L11 -7.8 RPS9 217747_s_at Hs.180920 ribosomal protein S9 -2.1 RPS9 214317_x_at Hs.180920 ribosomal protein S9 -1.4 -1.7 -1.7 -1.7 1.6 RPS25 200091_s_at Hs.409158 ribosomal protein S25 -2.3 RPS27A 200017_at Hs.311640 ribosomal protein S27a -2.1 -1.6 RUFY2 219957_at Hs.154091 RUN and FYVE domain containing 2 -9.1 SARA1 201542_at Hs.110796 SAR1a gene homolog 1 (S. cerevisiae) -3.1 SCAP 212329_at Hs.78442 SREBP cleavage-activating protien -16.5 -1.9 SCA7 204516_at Hs.108447 spinocerebellar ataxia 7 -9.9 SCA7 209964_s_at Hs.108447 spinocerebellar ataxia 7 -3.2 SCO2 205241_at Hs.278431 SCO cytochrome oxidase deficient homolog 2 -4.3 SDHB 202675_at Hs.64 succinate dehydrogenase complex -3.4 SEC6L1 212630_at Hs.8088 SEC6-like 1 (S. cerevisiae) -12.8 SEC24B 202798_at Hs.7239 SEC24 related gene family, member B (S. cerevisiae) -3.4 SELT 217811_at Hs.8148 selenoprotein T -2.3

19 SEP15 200902_at Hs.90606 15 kDa selenoprotein -3.0 SERP1 200971_s_at Hs.76698 stress-associated endoplasmic reticulum protein 1 -2.2 SIAT8D 206925_at Hs.367958 sialyltransferase 8D (alpha-2, 8-polysialyltransferase) -3.3 SLC16A6 207038_at Hs.114924 monocarboxylic acid transporters -11.2 SLC22A4 205896_at Hs.77239 organic cation transporter -2.3 SLC30A1 212907_at Hs.24385 zinc transporter -10.3 SLC39A6 202088_at Hs.79136 zinc transporter -2.7 SMS 202043_s_at Hs.89718 spermine synthase -2.4 SMT3H2 208739_x_at Hs.180139 SMT3 suppressor of mif two 3 homolog 2 (yeast) -2.9 SMT3H2 208738_x_at Hs.180139 SMT3 suppressor of mif two 3 homolog 2 (yeast) -2.1 SMT3H2 213879_at Hs.180139 SMT3 suppressor of mif two 3 homolog 2 (yeast) -1.2 -1.6 -1.8 SNAP23 209131_s_at Hs.184376 synaptosomal-associated protein, 23kDa -19.0 SNAP23 214544_s_at Hs.184376 synaptosomal-associated protein, 23kDa -2.2 SNAP23 209130_at Hs.184376 synaptosomal-associated protein, 23kDa -5.1 SNAP29 218327_s_at Hs.194714 synaptosomal-associated protein, 29kDa -3.6 SPC18 216274_s_at Hs.9534 signal peptidase complex (18kD) -4.2 SPC18 201290_at Hs.9534 signal peptidase complex (18kD) -3.9 SQRDL 217995_at Hs.8185 sulfide quinone reductase-like (yeast) -2.6 2.4 SSR1 200890_s_at Hs.250773 signal sequence receptor, alpha -9.3 SSR1 200889_s_at Hs.250773 signal sequence receptor, alpha -2.3 SSR1 200891_s_at Hs.250773 signal sequence receptor, alpha -5.1 STX6 212799_at Hs.157144 syntaxin 6 -3.5 STX7 212631_at Hs.8906 syntaxin 7 -2.5 STX7 212632_at Hs.8906 syntaxin 7 -2.5 STXBP2 209367_at Hs.379204 syntaxin binding protein 2 -5.1 ST3GALVI 213355_at Hs.34578 alpha2,3-sialyltransferase -3.0 SULT1A1 203615_x_at Hs.142 sulfotransferase family -3.9 SULT1A1 215299_x_at Hs.142 sulfotransferase family -3.0 -1.6 SUSP1 202318_s_at Hs.27197 SUMO-1-specific protease -4.9 SYNJ1 212990_at Hs.401730 synaptojanin 1 -3.8 TALDO1 201463_s_at Hs.77290 transaldolase 1 -2.6 TBCC 202495_at Hs.75064 tubulin-specific chaperone c -6.0 TCTEL1 201999_s_at Hs.266940 t-complex-associated-testis-expressed 1-like 1 -3.9 TGOLN2 212040_at Hs.110771 trans-golgi network protein 2 -4.9 TGOLN2 212043_at Hs.110771 trans-golgi network protein 2 -2.4 TIC 203317_at Hs.110121 SEC7 homolog -3.6 TIMP1 201666_at Hs.5831 tissue inhibitor of metalloproteinase 1 . -2.4 2.2 TM9SF2 201078_at Hs.28757 transmembrane 9 superfamily member 2 -2.5 TRAM 201398_s_at Hs.4147 translocating chain-associating membrane protein -2.4 TRAPPC3 203512_at Hs.288013 trafficking protein particle complex 3 -2.9 TPR 201731_s_at Hs.169750 translocated promoter region -2.0 KIAA0349 212760_at Hs.15303 ubiquitin ligase E3 alpha-II -5.1 UBA52 221700_s_at Hs.5308 ubiquitin A-52 residue ribosomal prot. fusion product 1 -3.1 UBE1 200964_at Hs.2055 ubiquitin-activating enzyme E1 -3.3 2.1 UBE1C 209115_at Hs.154320 ubiquitin-activating enzyme E1C -3.6 UBE1L 1294_at Hs.16695 ubiquitin-activating enzyme E1-like -2.1 UBE2D1 211764_s_at Hs.129683 ubiquitin-conjugating enzyme E2D 1 -2.1 UBE2D3 200668_s_at Hs.118797 ubiquitin-conjugating enzyme E2D 3 -2.2 UBE2D3 200667_at Hs.118797 ubiquitin-conjugating enzyme E2D 3 -3.3

20 UBE2G1 209142_s_at Hs.78563 ubiquitin-conjugating enzyme E2G 1 -9.6 2.0 UBE2I 213535_s_at Hs.84285 ubiquitin-conjugating enzyme E2I -2.5 2.0 UBE2L3 200683_s_at Hs.108104 ubiquitin-conjugating enzyme E2L 3 -14.6 UBE2L3 200682_s_at Hs.408569 ubiquitin-conjugating enzyme E2L 3 -2.7 2.0 UBE2L6 201649_at Hs.425777 ubiquitin-conjugating enzyme E2L 6 -2.3 UBE2E3 210024_s_at Hs.4890 ubiquitin-conjugating enzyme E2E 3 -4.8 UBL1 208761_s_at Hs.81424 ubiquitin-like 1 (sentrin) -2.6 UBL3 201534_s_at Hs.173091 ubiquitin-like 3 -3.4 UGP2 205480_s_at Hs.77837 UDP-glucose pyrophosphorylase 2 -2.4 UQCR 202090_s_at Hs.8372 ubiquinol-cytochrome c reductase (6.4kD) subunit -2.9 UQCRB 209066_x_at Hs.131255 ubiquinol-cytochrome c reductase binding protein -2.7 -1.5 UQCRB 205849_s_at Hs.131255 ubiquinol-cytochrome c reductase binding protein -2.6 UFD1L 209103_s_at Hs.199402 ubiquitin fusion degradation 1-like -6.3 USP1 202413_s_at Hs.35086 ubiquitin specific protease 1 -3.4 USP3 221654_s_at Hs.251636 ubiquitin specific protease 3 -2.6 USP4 211800_s_at Hs.77500 ubiquitin specific protease 4 (proto-oncogene) -2.5 USP7 201499_s_at Hs.78683 ubiquitin specific protease 7 (herpes virus-associated) -2.9 USP7 201498_at Hs.78683 ubiquitin specific protease 7 (herpes virus-associated) -3.5 USP10 209137_s_at Hs.78829 ubiquitin specific protease 10 -4.0 USP15 209475_at Hs.23168 ubiquitin specific protease 15 -2.5 USP15 210681_s_at Hs.23168 ubiquitin specific protease 15 -3.1 USP32 211702_s_at Hs.155787 ubiquitin specific protease 32 -2.1 USP33 212513_s_at Hs.173694 ubiquitin specific protease 33 -12.6 USP34 212066_s_at Hs.180948 ubiquitin specific protease 34 -2.5 VAPA 208780_x_at Hs.9006 VAMP-associated protein A -2.2 VCP 208649_s_at Hs.106357 valosin-containing protein -4.6 2.1 VDP 201832_s_at Hs.325948 vesicle docking protein p115 -3.0 VNN3 220528_at Hs.183656 vanin 3 -11.4 2.6 VPS28 218679_s_at Hs.339697 vacuolar protein sorting 28 (yeast) -25.6 VPS28 212090_at Hs.339697 vacuolar protein sorting 28 (yeast) 3.7 1.6 WWP2 204022_at Hs.333382 Nedd-4-like ubiquitin-protein ligase -2.4 XPO1 208775_at Hs.79090 exportin 1 (CRM1 homolog, yeast) -2.0 XPO6 211982_x_at Hs.70500 exportin 6 -4.6 ZMPSTE24 202939_at Hs.25846 zinc metalloproteinase (STE24 homolog, yeast) -2.3

Cytokines, chemokines, and growth factors Up-regulated (11) CSF1 209716_at Hs.173894 colony stimulating factor 1 3.5 CXCL12 203666_at Hs.237356 chemokine (C-X-C motif) ligand 12 2.3 EGFL6 219454_at Hs.12844 EGF-like-domain, multiple 6 2.4 FGF7 205782_at Hs.374988 fibroblast growth factor 7 2.4 1.9 FGF18 214284_s_at Hs.49585 fibroblast growth factor 18 2.2 IFNA7 208259_x_at Hs.282274 interferon, alpha 7 2.4 IFNA14 208182_x_at Hs.93907 interferon, alpha 14 2.1 IFNA17 211405_x_at Hs.282276 interferon, alpha 17 2.5 IFNG 210354_at Hs.856 interferon, gamma 2.1 IL15 205992_s_at Hs.168132 interleukin 15 2.9 LECT1 206309_at Hs.97932 leukocyte cell derived chemotaxin 1 2.3

21 Down-regulated (7) CKLF 221058_s_at Hs.15159 chemokine-like factor -17.0 -1.9 CKLF 219161_s_at Hs.15159 chemokine-like factor -5.5 EGFL5 212830_at Hs.5599 EGF-like-domain, multiple 5 -7.5 IK 200066_at Hs.8024 IK cytokine, down-regulator of HLA II -7.3 IL16 209827_s_at Hs.82127 interleukin 16 -2.3 LTB 207339_s_at Hs.890 lymphotoxin beta (TNF superfamily, member 3) -9.5 PBEF 217738_at Hs.239138 pre-B-cell colony-enhancing factor -2.7 TGFB1 203085_s_at Hs.1103 transforming growth factor, beta 1 -3.1

Cell adhesion and host defense Up-regulated (61) ACTA2 215787_at Hs.269926 actin, alpha 2, smooth muscle, aorta 2.2 ACTN2 203864_s_at Hs.83672 actinin, alpha 2 2.1 ADAMDEC1 206134_at Hs.145296 a disintegrin-like and metalloprotease-like, decysin 1 3.2 ADAMTS3 214913_at Hs.27916 a disintegrin-like and metalloprotease 2.4 ADAMTS9 220287_at Hs.318751 a disintegrin-like and metalloprotease 2.2 ADAMTS20 220717_at Hs.287554 a disintegrin-like and metalloprotease 3.0 ADAM21 207665_at Hs.178748 a disintegrin and metalloproteinase domain 21 2.6 AKAP6 205359_at Hs.89666 A kinase (PRKA) anchor protein 6 2.1 AMELX 208410_x_at Hs.46329 amelogenin (X chrom., amelogenesis imperfecta 1) 2.1 ATRN 212517_at Hs.194019 attractin 2.4 CDH11 207173_x_at Hs.75929 cadherin 11, type 2, OB-cadherin (osteoblast) 2.5 COL11A2 216993_s_at collagen, type XI, alpha 2 2.1 COL15A1 203477_at Hs.83164 collagen, type XV, alpha 1 3.6 1.7 CR1 217484_at Hs.193716 complement component (3b/4b) receptor 1 2.3 CR1 217552_x_at Hs.193716 complement component (3b/4b) receptor 1 -2.0 -1.9 1.6 -1.7 -1.6 CSPG2 221731_x_at Hs.81800 chondroitin sulfate proteoglycan 2 (versican) 2.1 -1.7 -1.8 -2.5 -2.0 CSPG3 205143_at Hs.169047 chondroitin sulfate proteoglycan 3 (neurocan) 2.9 CTNNA1 215883_at Hs.288481 catenin (cadherin-associated protein), alpha 1, 102 kDa 2.0 CTNNA1 210844_x_at Hs.177556 catenin (cadherin-associated protein), alpha 1, 102 kDa -4.7 2.6 CYLC1 216809_at Hs.307358 cylicin, basic protein of sperm head cytoskeleton 1 2.2 DMN 212730_at Hs.10587 desmuslin 2.3 1.6 DNAH17 214229_at Hs.144672 dynein, axonemal, heavy polypeptide 17 7.6 DTNA 205741_s_at Hs.336678 dystrobrevin, alpha 2.2 EPLIN 217892_s_at Hs.10706 epithelial protein lost in neoplasm beta 2.1 FBLN1 207835_at Hs.79732 fibulin 1 2.1 FGL1 205305_at Hs.107 fibrinogen-like 1 2.2 FLRT2 204359_at Hs.48998 fibronectin leucine rich transmembrane protein 2 2.2 -1.8 -4.3 HAMP 220491_at Hs.8821 hepcidin antimicrobial peptide 2.4 HMMR 209709_s_at Hs.72550 hyaluronan-mediated motility receptor (RHAMM) 2.3 IF 203854_at Hs.36602 I factor (complement) 2.8 ITGA10 206766_at Hs.158237 integrin, alpha 10 2.3 ITGB8 211488_s_at Hs.355722 integrin, beta 8 2.2 KERA 220504_at Hs.125750 keratocan 3.6 KRT2A 207908_at Hs.707 keratin 2A (epidermal ichthyosis bullosa of Siemens) 2.3 LAMB3 209270_at Hs.75517 laminin, beta 3 16.1 MAP1B 212233_at Hs.82503 microtubule-associated protein 1B 2.3 MID2 208384_s_at Hs.12256 midline 2 2.6

22 MMRN2 219091_s_at Hs.127216 multimerin 2 2.5 MYL5 205144_at Hs.170482 myosin, light polypeptide 5, regulatory 2.4 MYO1B 212365_at Hs.121576 myosin IB 2.0 MYO5C 218966_at Hs.111782 myosin 5C 2.0 MYO15A 220288_at Hs.127561 myosin XVA 2.3 NLGN1 205893_at Hs.71132 neuroligin 1 2.7 NRCAM 216959_x_at Hs.7912 neuronal cell adhesion molecule 3.2 OSF-2 210809_s_at Hs.136348 osteoblast specific factor 2 (fasciclin I-like) 2.4 PCDH17 205656_at Hs.106511 protocadherin 17 2.3 PGLYRPIbeta 220944_at Hs.58356 peptidoglycan recognition protein-I-beta precursor 2.3 PLGL 205871_at Hs.406278 plasminogen-like 2.3 PLS3 201215_at Hs.4114 plastin 3 (T isoform) 2.7 -2.6 -1.7 -1.6 -1.6 POMZP3 210910_s_at Hs.273790 POM (POM121 homolog, rat) and ZP3 fusion 2.2 PRG4 206007_at Hs.432458 proteoglycan 4 2.6 SFTPB 213936_x_at Hs.264330 surfactant, pulmonary-associated protein B 2.5 SIGLEC6 210796_x_at Hs.117992 sialic acid binding Ig-like lectin 6 2.3 SPAG9 212470_at Hs.129872 sperm associated antigen 9 2.4 SPAM1 216989_at Hs.121494 sperm adhesion molecule 1 2.5 SPTA1 206937_at Hs.1985 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 2.1 -2.8 SPTBN1 212071_s_at Hs.107164 spectrin, beta, non-erythrocytic 1 5.8 SRPX 204955_at Hs.15154 sushi-repeat-containing protein, X chromosome 2.1 STOM 201060_x_at Hs.160483 stomatin 2.5 THBS1 215775_at Hs.164226 thrombospondin 1 2.3 TMPO 203432_at Hs.406660 thymopoietin 2.3 TMPO 209753_s_at Hs.406660 thymopoietin 2.0 TMPO 209754_s_at Hs.406660 thymopoietin 2.4 TMSNB 205347_s_at Hs.56145 thymosin, beta, identified in neuroblastoma cells 2.3 1.5 cig5 213797_at Hs.17518 vipirin 4.7 1.7

Down-regulated (61) ACTG1 213214_x_at Hs.14376 actin, gamma 1 -2.9 ACTG1 211995_x_at Hs.14376 actin, gamma 1 -2.8 ACTG1 212363_x_at Hs.14376 actin, gamma 1 -2.7 ACTG1 221607_x_at Hs.14376 actin, gamma 1 -2.3 ACTG1 211983_x_at Hs.14376 actin, gamma 1 -2.5 ACTN1 208637_x_at Hs.119000 actinin, alpha 1 -3.0 ACTN1 208636_at Hs.119000 actinin, alpha 1 -2.3 ACTN4 200601_at Hs.182485 actinin, alpha 4 -2.0 -1.8 ADAM8 205180_s_at Hs.86947 a disintegrin and metalloproteinase domain 8 -2.8 -1.6 ADAM10 202603_at Hs.172028 a disintegrin and metalloproteinase domain 10 -2.4 ADD1 208030_s_at Hs.183706 adducin 1 (alpha) -2.4 ADD1 214736_s_at Hs.183706 adducin 1 (alpha) -3.5 ADD1 214726_x_at Hs.183706 adducin 1 (alpha) 1.2 -1.6 ADRM1 201281_at Hs.90107 adhesion regulating molecule 1 -2.3 BECN1 208946_s_at Hs.12272 beclin 1 (coiled-coil, myosin-like BCL2 interact. prot.) -5.9 CAPZB 201949_x_at Hs.333417 capping protein (actin filament) muscle Z-line, beta -2.1 CAPZB 37012_at Hs.333417 capping protein (actin filament) muscle Z-line, beta -2.4 CHS1 203518_at Hs.36508 Chediak-Higashi syndrome 1 -7.6 2.1 COL18A1 209081_s_at Hs.78409 collagen, type XVIII, alpha 1 -19.8 -1.7

23 CORO1A 209083_at Hs.109606 coronin, actin binding protein, 1A -73.3 -1.6 CTSS 202902_s_at Hs.181301 cathepsin S -4.7 DCN 201894_s_at Hs.433989 decorin -2.6 DNCLI1 217976_s_at Hs.266483 dynein, cytoplasmic, light intermediate polypeptide 1 -8.2 DNM2 202253_s_at Hs.167013 dynamin 2 -18.8 ELMO1 204513_s_at Hs.31463 engulfment and cell motility 1 (ced-12 hom., C. elegans) -4.2 ELMO2 55692_at Hs.96560 engulfment and cell motility 2 (ced-12 hom., C. elegans) -5.4 FGL2 204834_at Hs.351808 fibrinogen-like 2 -12.7 -1.7 FHOD1 218530_at Hs.95231 formin homology 2 domain containing 1 -4.4 1.5 2.1 FLII 222065_s_at Hs.83849 flightless I homolog (Drosophila) -18.1 1.8 3.5 FLOT2 201350_at Hs.184488 flotillin 2 -2.4 FMNL 204789_at Hs.100217 formin-like -11.1 2.8 F5 204714_s_at Hs.30054 coagulation factor V (proaccelerin, labile factor) -2.2 -1.8 GSN 200696_s_at Hs.290070 gelsolin (amyloidosis, Finnish type) -2.7 HBXIP 202299_s_at Hs.433355 hepatitis B virus x interacting protein -2.7 HBXIP 202300_at Hs.433355 hepatitis B virus x interacting protein -2.7 HOM-TES-103 209721_s_at Hs.46659 HOM-TES-103 tumor antigen-like -2.1 K-ALPHA-1 211072_x_at Hs.334842 tubulin, alpha, ubiquitous -4.9 K-ALPHA-1 211058_x_at Hs.334842 tubulin, alpha, ubiquitous -4.9 K-ALPHA-1 201090_x_at Hs.334842 tubulin, alpha, ubiquitous -3.8 K-ALPHA-1 213646_x_at Hs.334842 tubulin, alpha, ubiquitous -3.3 K-ALPHA-1 212639_x_at Hs.334842 tubulin, alpha, ubiquitous -2.7 KLHL2 219157_at Hs.122967 kelch-like 2, Mayven (Drosophila) -2.3 KNS2 213656_s_at Hs.274440 kinesin 2 60/70kDa -4.0 KRT10 213287_s_at Hs.99936 keratin 10 -2.4 LAMP2 200821_at Hs.8262 lysosomal-associated membrane protein 2 -2.1 LAMP2 203041_s_at Hs.8262 lysosomal-associated membrane protein 2 -3.6 2.0 MRCL3 201318_s_at Hs.180224 myosin regulatory light chain MRCL3 -3.1 -1.6 MSN 200600_at Hs.170328 moesin -3.0 MYO1F 213733_at Hs.406409 myosin IF -7.4 MYH9 211926_s_at Hs.146550 myosin, heavy polypeptide 9, non-muscle -4.2 NCF1 204961_s_at Hs.1583 neutrophil cytosolic factor 1 (p47phox) -23.1 NCF1 214084_x_at Hs.1583 neutrophil cytosolic factor 1 (p47phox) -11.3 2.8 NCF4 207677_s_at Hs.196352 neutrophil cytosolic factor 4, (p40phox) -2.3 NICAL 218376_s_at Hs.33476 NEDD9 interacting protein -4.3 -1.5 NINJ2 219594_at Hs.380976 ninjurin 2 -19.4 2.6 PFC 206380_s_at Hs.53155 properdin P factor, complement -17.7 5.4 PFN1 200634_at Hs.408943 profilin 1 -2.3 2.4 PLXNC1 206470_at Hs.286229 plexin C1 -6.0 2.4 PXN 201087_at Hs.102497 paxillin -2.6 RAP1A 202362_at Hs.865 member of RAS oncogene family -3.1 RNASE6PL 217983_s_at Hs.8297 ribonuclease 6 precursor -9.4 -1.6 SELL 204563_at Hs.82848 selectin L (lymphocyte adhesion molecule 1) -5.0 SELPLG 209879_at Hs.79283 selectin P ligand -13.7 SELPLG 209880_s_at Hs.79283 selectin P ligand -3.7 SVIL 202566_s_at Hs.154567 supervillin -2.2 S100A4 203186_s_at Hs.81256 S100 calcium binding protein A4 -13.4 -1.8 S100A6 217728_at Hs.275243 S100 calcium binding protein A6 (calcyclin) -3.6 -1.6 THBS1 201110_s_at Hs.87409 thrombospondin 1 -9.9

24 TMSB10 217733_s_at Hs.76293 thymosin, beta 10 -3.6 TUBA1 212242_at Hs.75318 tubulin, alpha 1 (testis specific) -6.2 -1.9 TUBA3 209118_s_at Hs.433394 tubulin, alpha 3 -4.0 TUBA6 209251_x_at Hs.406578 tubulin alpha 6 -2.5 TUBA6 211750_x_at Hs.406578 tubulin alpha 6 -5.2 TUBB2 208977_x_at Hs.251653 tubulin, beta, 2 -2.6 2.3 VCL 200931_s_at Hs.75350 vinculin -2.1 WASF2 221725_at Hs.288908 WAS protein family, member 2 -4.5 WASPIP 202664_at Hs.24143 Wiskott-Aldrich syndrome protein interacting protein -3.5 WASPIP 202663_at Hs.24143 Wiskott-Aldrich syndrome protein interacting protein -5.2 WASPIP 202665_s_at Hs.379203 Wiskott-Aldrich syndrome protein interacting protein -2.5 ZYX 215706_x_at Hs.75873 zyxin -4.4

Receptors and signal transduction Up-regulated (81) ACVR2 205327_s_at Hs.26014 activin A receptor, type II 2.4 AGTR1 205357_s_at Hs.89472 angiotensin II receptor, type 1 2.6 AR 211621_at Hs.99915 androgen receptor 2.2 ARHGDIA 211716_x_at Hs.159161 Rho GDP dissociation inhibitor (GDI) alpha 2.0 CAV2 203323_at Hs.397414 caveolin 2 3.2 CASK 211208_s_at Hs.151469 calcium/calmodulin-dependent serine protein kinase 2.4 CCR9 207445_s_at Hs.225946 chemokine (C-C motif) receptor 9 2.5 -1.5 -2.2 CD63 200663_at Hs.433996 CD63 antigen (melanoma 1 antigen) 2.7 CD69 209795_at Hs.82401 CD69 antigen (p60, early T-cell activation antigen) 2.2 1.7 CD83 204440_at Hs.79197 CD83 antigen 12.4 CD84 211189_x_at Hs.137548 CD84 antigen (leukocyte antigen) 2.4 CHRNA5 206533_at Hs.1614 cholinergic receptor, nicotinic, alpha polypeptide 5 2.4 CHRNA6 207568_at Hs.103128 cholinergic receptor, nicotinic, alpha polypeptide 6 2.6 CLECSF9 219859_at Hs.236516 C-type lectin, superfamily member 9 2.4 1.8 CNR1 213436_at Hs.75110 cannabinoid receptor 1 (brain) 2.2 DAMS 220263_at Hs.59666 SMAD in the antisense orientation 2.3 1.6 DOK5 214844_s_at Hs.127751 docking protein 5 3.2 EGFR 211551_at Hs.77432 epidermal growth factor receptor 2.5 ERAL1 212087_s_at Hs.3426 Era G-protein-like 1 (E. coli) 2.8 1.6 FGD1 204819_at Hs.1572 faciogenital dysplasia (Aarskog-Scott syndrome) 2.8 FZD6 203987_at Hs.114218 frizzled homolog 6 (Drosophila) 3.3 -1.7 -2.6 GAS 208138_at Hs.2681 gastrin 2.0 GPR32 221469_at Hs.248125 G protein-coupled receptor 32 2.7 GPR58 221394_at Hs.272382 G protein-coupled receptor 58 2.1 -1.7 GPR116 212950_at Hs.362806 G protein-coupled receptor 116 2.6 GPR126 213094_at Hs.44197 G protein-coupled receptor 126 2.8 HFE 210864_x_at Hs.20019 hemochromatosis 2.1 HFE 211863_x_at Hs.20019 hemochromatosis 2.1 HFE 206087_x_at Hs.20019 hemochromatosis 2.3 -1.7 -2.0 HIPK3 213697_at Hs.30148 homeodomain interacting protein kinase 3 2.5 HM74 205220_at Hs.137555 putative chemokine receptor; GTP-binding protein 7.4 HTR2C 211479_s_at Hs.46362 5-hydroxytryptamine (serotonin) receptor 2C 2.1 ILF3 208931_s_at Hs.256583 interleukin enhancer binding factor 3, 90kDa 2.3 IL6ST 204864_s_at Hs.82065 interleukin 6 signal transducer (oncostatin M receptor) 2.6

25 IL22RA1 220056_at Hs.110915 interleukin 22 receptor, alpha 1 2.5 -1.7 -1.7 INHBC 207687_at Hs.374664 inhibin, beta C 2.3 INHBC 207688_s_at Hs.374664 inhibin, beta C 2.0 IRAK1 201587_s_at Hs.182018 interleukin-1 receptor-associated kinase 1 3.7 ITGB3BP 205176_s_at Hs.405465 integrin beta 3 binding protein (beta3-endonexin) 2.4 KLRG1 210288_at Hs.146322 killer cell lectin-like receptor subfamily G, member 1 2.0 LEFTB 206268_at Hs.278239 left-right determination, factor B 2.4 LGALS3 208949_s_at Hs.621 lectin, galactoside-binding, soluble, 3 (galectin 3) 8.0 LPHN3 209866_s_at Hs.21917 latrophilin 3 2.3 MAPK13 210059_s_at Hs.178695 mitogen-activated protein kinase 13 3.6 MAP2K3 215499_at Hs.180533 mitogen-activated protein kinase kinase 3 2.7 MS4A2 207497_s_at Hs.30 membrane-spanning 4-domains, subfamily A, member 2 2.7 NOTCH4 205247_at Hs.11689 Notch homolog 4 (Drosophila) 2.0 NTRK2 207152_at Hs.47860 neurotrophic tyrosine kinase, receptor, type 2 2.0 NTRK3 217033_x_at Hs.26776 neurotrophic tyrosine kinase, receptor, type 3 2.3 NTRK3 217377_x_at Hs.26776 neurotrophic tyrosine kinase, receptor, type 3 2.4 OLR1 210004_at Hs.77729 oxidised low density lipoprotein (lectin-like) receptor 1 2.0 1.8 OPHN1 206323_x_at Hs.128824 oligophrenin 1 2.2 -3.6 OR1E1 214515_at Hs.278485 olfactory receptor, family 1, subfamily E, member 1 2.7 OR1E1 214515_at Hs.278485 olfactory receptor, family 1, subfamily E, member 1 2.7 -2.2 OR2W1 221451_s_at Hs.247854 olfactory receptor, family 2, subfamily W, member 1 2.3 OR7E24P 215463_at Hs.129832 olfactory receptor pseudogene 2.3 OR12D2 221344_at Hs.247862 olfactory receptor, family 12, subfamily D, member 2 2.1 PARG1 203910_at Hs.70983 PTPL1-associated RhoGAP 1 2.4 PLAUR 210845_s_at Hs.179657 plasminogen activator, urokinase receptor 3.4 PLAUR 211924_s_at Hs.179657 plasminogen activator, urokinase receptor 4.0 PLXNA2 213030_s_at Hs.300622 plexin A2 2.1 PLXDC1 214081_at Hs.125036 plexin domain containing 1 2.2 PLSCR1 202446_s_at Hs.198282 phospholipid scramblase 1 2.9 PPP1R9A 221088_s_at Hs.247748 protein phosphatase 1, regulatory (inhibitor) subunit 9A 2.6 -2.0 PRKAA2 207709_at Hs.2329 protein kinase, AMP-activated, alpha 2 catalytic subunit 3.8 PRKAB2 214474_at Hs.50732 protein kinase, AMP-activated, beta 2 non-catalytic sub. 2.1 PRKCI 209677_at Hs.1904 protein kinase C, iota 2.4 PRL 205445_at Hs.1905 prolactin 2.2 PTCRA 211252_x_at Hs.169002 pre-T-cell receptor alpha precursor 3.5 PTCRA 215492_x_at Hs.169002 pre-T-cell receptor alpha precursor 2.4 PTGER3 208169_s_at Hs.170917 prostaglandin E receptor 3 (subtype EP3) 2.0 -2.0 PTGER4 204897_at Hs.199248 prostaglandin E receptor 4 (subtype EP4) 4.5 1.5 PTPRB 217177_s_at Hs.149770 protein tyrosine phosphatase, receptor type, B 3.1 PTPRK 203038_at Hs.79005 protein tyrosine phosphatase, receptor type, K 3.0 P2RY4 221466_at Hs.248157 pyrimidinergic receptor P2Y, G-protein coupled, 4 2.0 RIMS2 215478_at Hs.153610 regulating synaptic membrane exocytosis 2 2.1 -2.4 -2.0 ROCK2 211504_x_at Hs.58617 Rho-associated, coiled-coil containing protein kinase 2 2.5 1.6 SCARF1 206995_x_at Hs.57735 scavenger receptor class F, member 1 2.4 SFN 33322_i_at Hs.184510 stratifin 2.1 SFN 33323_r_at Hs.184510 stratifin 2.3 SH3GL3 205636_at Hs.80315 SH3-domain GRB2-like 3 2.4 SH3GL3 211565_at Hs.80315 SH3-domain GRB2-like 3 2.5 -2.1 -1.8 SOCS4 214462_at Hs.44439 suppressor of cytokine signaling 4 2.9

26 SOCS5 209647_s_at Hs.169836 suppressor of cytokine signaling 5 2.1 STAT5A 203010_at Hs.167503 signal transducer and activator of transcription 5A 2.0 TNIK 213109_at Hs.170204 TRAF2 and NCK interacting kinase 2.1 TNFRSF14 209354_at Hs.279899 TNF receptor superfamily, member 14 2.1 TRIP10 202734_at Hs.73999 thyroid hormone receptor interactor 10 2.6 VN1R1 221412_at Hs.287372 vomeronasal 1 receptor 1 2.5 WNT6 71933_at Hs.29764 wingless-type MMTV integration site family, member 6 2.0

Down-regulated (228) AAK1 205434_s_at Hs.135941 adaptor-associated kinase 1 -2.8 ACP33 217827_s_at Hs.71475 acid cluster protein 33 -2.4 ACTR2 200729_s_at Hs.393201 ARP2 actin-related protein 2 homolog (yeast) -4.0 ACTR2 200728_at Hs.396278 ARP2 actin-related protein 2 homolog (yeast) -4.3 ACTR10 222230_s_at Hs.274369 actin-related protein 10 homolog (S. cerevisiae) -19.7 ADCY7 203741_s_at Hs.172199 adenylate cyclase 7 -22.0 ADRBK1 201401_s_at Hs.83636 adrenergic, beta, receptor kinase 1 -24.3 ANP32A 201043_s_at Hs.285013 acidic (leucine-rich) nuclear phosphoprotein 32 family -12.0 ANP32B 201306_s_at Hs.84264 acidic (leucine-rich) nuclear phosphoprotein 32 family -3.3 ANP32B 201305_x_at Hs.84264 acidic (leucine-rich) nuclear phosphoprotein 32 family -2.4 -1.7 -1.7 ANXA11 206200_s_at Hs.75510 annexin A11 -16.6 ANXA11 214783_s_at Hs.75510 annexin A11 -6.7 APOB48R 220023_at Hs.200333 apolipoprotein B48 receptor -2.9 ARAP3 218950_at Hs.25277 plekstrin homology domains-containing protein -5.4 ARF1 200065_s_at Hs.74571 ADP-ribosylation factor 1 -2.2 ARF3 200011_s_at Hs.119177 ADP-ribosylation factor 3 -2.7 ARF5 201526_at Hs.430657 ADP-ribosylation factor 5 -7.6 ARHA 200059_s_at Hs.77273 ras homolog gene family, member A -2.1 ARHB 212099_at Hs.204354 ras homolog gene family, member B -4.0 ARHQ 212119_at Hs.250697 ras homolog gene family, member Q -2.4 2.1 ARHQ 212117_at Hs.250697 ras homolog gene family, member Q -1.5 2.2 ARL7 202208_s_at Hs.111554 ADP-ribosylation factor-like 7 -11.5 ARPC1B 201954_at Hs.433506 actin related protein 2/3 complex, subunit 1B, 41kDa -3.4 ARPC2 208679_s_at Hs.83583 actin related protein 2/3 complex, subunit 2, 34kDa -4.3 ARPC2 207988_s_at Hs.83583 actin related protein 2/3 complex, subunit 2, 34kDa -4.3 ARPC2 213513_x_at Hs.83583 actin related protein 2/3 complex, subunit 2, 34kDa -2.9 ARPC3 208736_at Hs.293750 actin related protein 2/3 complex, subunit 3, 21kDa -5.4 ARPC5 211963_s_at Hs.82425 actin related protein 2/3 complex, subunit 5, 16kDa -2.6 ARHGEF6 209539_at Hs.79307 Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 -8.5 -1.5 ARHGDIB 201288_at Hs.83656 Rho GDP dissociation inhibitor (GDI) beta -7.7 -1.6 ARHGAP15 218870_at Hs.177812 ARHGAP15 -5.5 ARHGAP1 202117_at Hs.138860 Rho GTPase activating protein 1 -5.6 ARHT1 218323_at Hs.14202 ras homolog gene family, member T1 -3.4 -1.6 ARRB2 203388_at Hs.18142 arrestin, beta 2 -11.1 BAT2 208132_x_at Hs.25911 HLA-B associated transcript 2 -4.7 BTN3A1 209770_at Hs.284283 butyrophilin, subfamily 3, member A1 -26.0 -1.5 BTN3A3 204820_s_at Hs.167741 butyrophilin, subfamily 3, member A3 -19.0 -1.7 BTN3A3 204821_at Hs.167741 butyrophilin, subfamily 3, member A3 -20.3 BTN3A3 38241_at Hs.167741 butyrophilin, subfamily 3, member A3 -32.1 2.3 Cab45 221972_s_at Hs.42806 calcium binding protein Cab45 precursor -7.2 2.2

27 Cab45 217855_x_at Hs.42806 calcium binding protein Cab45 precursor -2.3 CALM1 200653_s_at Hs.282410 calmodulin 1 (phosphorylase kinase, delta) -17.5 CALM1 200655_s_at Hs.282410 calmodulin 1 (phosphorylase kinase, delta) -2.9 CALM2 207243_s_at Hs.425808 calmodulin 2 (phosphorylase kinase, delta) -5.2 CALM3 200623_s_at Hs.334330 calmodulin 3 (phosphorylase kinase, delta) -14.8 CALM3 200622_x_at Hs.334330 calmodulin 3 (phosphorylase kinase, delta) -2.7 CAP1 200625_s_at Hs.104125 CAP, adenylate cyclase-associated protein 1 (yeast) -4.1 CAP1 213798_s_at Hs.104125 CAP, adenylate cyclase-associated protein 1 (yeast) -2.3 CCR3 208304_at Hs.158324 chemokine (C-C motif) receptor 3 -7.6 -1.9 CD9 201005_at Hs.1244 CD9 antigen (p24) -12.0 -1.6 CD37 204192_at Hs.153053 CD37 antigen -4.6 CD47 213857_s_at Hs.446414 CD47 antigen -2.4 CD74 209619_at Hs.84298 CD74 antigen -4.6 2.6 CD164 208405_s_at Hs.43910 CD164 antigen, sialomucin -2.1 CHC1L 204759_at Hs.27007 chromosome condensation 1-like -9.1 CHRNE 214246_x_at Hs.112028 cholinergic receptor, nicotinic, epsilon polypeptide -2.0 CKIP-1 218223_s_at Hs.173380 casein kinase-2 interacting protein 1 -13.9 CLECSF6 221724_s_at Hs.115515 C-type lectin, superfamily member 6 -4.3 CLECSF6 219947_at Hs.115515 C-type lectin, superfamily member 6 -3.9 2.2 CLECSF12 221698_s_at Hs.161786 C-type lectin, superfamily member 12 -5.2 -1.9 CRLF3 205474_at Hs.7120 cytokine receptor-like factor 3 -2.9 CSF2RA 210340_s_at Hs.182378 CD116, GM-CDF receptor alpha -5.8 CSF3R 203591_s_at Hs.2175 CD114, G-CSF receptor -6.7 -1.7 CSK 202329_at Hs.77793 c-src tyrosine kinase -9.9 C1QR1 202878_s_at Hs.97199 complement component 1, q subcomponent, receptor 1 -2.2 DAPP1 219290_x_at Hs.62643 dual adaptor of phosphotyr. and 3-phosphoinositides -2.2 DGKZ 207556_s_at Hs.277445 diacylglycerol kinase, zeta 104kDa -17.7 DOCK2 213160_at Hs.17211 dedicator of cyto-kinesis 2 -5.5 DUSP6 208892_s_at Hs.180383 dual specificity phosphatase 6 -4.2 DUSP6 208891_at Hs.180383 dual specificity phosphatase 6 -6.3 2.4 DUSP11 202703_at Hs.14611 dual specificity phosphatase 11 -5.2 EDG4 206722_s_at Hs.122575 lysophosphatidic acid G-protein-coupled receptor, 4 -4.1 EDG4 206723_s_at Hs.122575 lysophosphatidic acid G-protein-coupled receptor, 4 -3.9 EMR2 207610_s_at Hs.137354 egf-like module containing, mucin-like receptor 2 -5.4 EMR3 210724_at Hs.326777 egf-like module-containing mucin-like receptor 3 -4.1 -1.5 ENIGMA 203370_s_at Hs.102948 enigma (LIM domain protein) -2.2 EPS15 217886_at Hs.79095 epidermal growth factor receptor pathway substrate 15 -7.5 EPS15 217887_s_at Hs.79095 epidermal growth factor receptor pathway substrate 15 -2.7 EVI2A 204774_at Hs.70499 ecotropic viral integration site 2A -5.1 EVI2B 211742_s_at Hs.5509 ecotropic viral integration site 2B -10.2 FCGR2A 210992_x_at Hs.78864 CD32 -17.4 1.5 FCGR2A 203561_at Hs.78864 CD32 -3.1 FCGR2B 211395_x_at Hs.397074 CD32 -2.7 FCGRT 218831_s_at Hs.111903 Fc fragment of IgG, receptor, transporter, alpha -13.2 FKBP1A 200709_at Hs.380080 FK506 binding protein 1A, 12kDa -5.2 FKBP1A 214119_s_at Hs.380080 FK506 binding protein 1A, 12kDa -2.1 FKBP1A 210186_s_at Hs.380080 FK506 binding protein 1A, 12kDa -3.3 FKBP11 219117_s_at Hs.24048 FK506 binding protein 11, 19 kDa -4.8 FNTA 200090_at Hs.356463 farnesyltransferase, CAAX box, alpha -3.2

28 FPRL1 210773_s_at Hs.99855 formyl peptide receptor-like 1 -2.4 1.6 FRAT2 209864_at Hs.140720 frequently rearranged in advanced T-cell lymphomas 2 -12.0 FYB 211795_s_at Hs.58435 FYN binding protein (FYB-120/130) -19.8 GABARAPL1 208868_s_at Hs.336429 GABA(A) receptor-associated protein like 1 -2.5 GABARAPL1 208869_s_at Hs.336429 GABA(A) receptor-associated protein like 1 -2.4 GABARAPL3 211458_s_at Hs.334497 GABA(A) receptors associated protein like 3 -5.7 GBP1 202269_x_at Hs.62661 guanylate binding protein 1, interferon-inducible, 67kDa -4.7 1.9 4.1 GBP2 202748_at Hs.171862 guanylate binding protein 2, interferon-inducible -3.7 GCA 203765_at Hs.79381 grancalcin, EF-hand calcium binding protein -2.8 GDI2 200009_at Hs.56845 GDP dissociation inhibitor 2 -5.0 GIT2 204982_at Hs.57734 G protein-coupled receptor kinase-interactor 2 -21.8 GMFG 204220_at Hs.5210 glia maturation factor, gamma -7.3 GNAI2 201040_at Hs.77269 G protein, alpha inhibiting activity polypeptide 2 -8.8 GNAI3 201179_s_at Hs.73799 G protein, alpha inhibiting activity polypeptide 3 -2.6 GNAS 212273_x_at Hs.374523 GNAS complex locus -3.8 GNAS 214548_x_at Hs.374523 GNAS complex locus -2.8 GNAS 211858_x_at Hs.374523 GNAS complex locus -3.1 GNAS 200780_x_at Hs.374523 GNAS complex locus -3.3 GNAS 200981_x_at Hs.374523 GNAS complex locus -3.4 GPR44 206361_at Hs.299567 G protein-coupled receptor 44 -2.9 GPR86 220005_at Hs.13040 G protein-coupled receptor 86 -56.4 2.0 GPR105 206637_at Hs.2465 G protein-coupled receptor 105 -7.6 GPR107 211979_at Hs.6639 G protein-coupled receptor 107 -8.8 GPS2 209350_s_at Hs.7301 G protein pathway suppressor 2 -2.7 2.1 HGS 210428_s_at Hs.12540 hepatocyte growth factor-regulated Tyr kinase substrate -2.2 HINT1 208826_x_at Hs.256697 histidine triad nucleotide binding protein 1 -2.6 HLA-C 211799_x_at Hs.277477 major histocompatibility complex, class I, C -2.5 HLA-F 204806_x_at Hs.110309 major histocompatibility complex, class I, F -2.1 HSOBRGRP 202378_s_at Hs.23581 leptin receptor gene-related protein -4.9 ICAM3 204949_at Hs.99995 intercellular adhesion molecule 3 -9.6 -1.7 IFIT1 203153_at Hs.20315 interferon-induced prot. with tetratricopeptide repeats 1 -9.1 IFIT2 217502_at Hs.169274 interferon-induced prot. with tetratricopeptide repeats 2 -3.0 IFIT4 204747_at Hs.181874 interferon-induced prot. with tetratricopeptide repeats 4 -2.3 IFITM1 201601_x_at Hs.366 interferon induced transmembrane protein 1 (9-27) -3.7 IFITM1 201601_x_at Hs.366 interferon induced transmembrane protein 1 (9-27) -3.7 IFITM1 214022_s_at Hs.366 interferon induced transmembrane protein 1 (9-27) -2.0 IGF1R 203627_at Hs.239176 insulin-like growth factor 1 receptor -2.3 IGF2R 201392_s_at Hs.76473 insulin-like growth factor 2 receptor -2.6 IHPK2 218192_at Hs.323432 inositol hexaphosphate kinase 2 -2.2 IL1RAP 205227_at Hs.173880 interleukin 1 receptor accessory protein -4.4 ILT8 208594_x_at Hs.306230 leukocyte Ig-like receptor -2.3 IL17R 205707_at Hs.129751 interleukin 17 receptor -6.1 IQGAP1 210840_s_at Hs.1742 IQ motif containing GTPase activating protein 1 -3.0 IQGAP1 200791_s_at Hs.1742 IQ motif containing GTPase activating protein 1 -11.3 2.3 IRAK1BP1 213074_at Hs.9927 IL-1 receptor-associated kinase 1 binding protein 1 -2.2 IRS2 209185_s_at Hs.143648 insulin receptor substrate 2 -2.6 ISGF3G 203882_at Hs.1706 interferon-stimulated transcription factor 3, gamma -2.2 2.1 ITGB2 202803_s_at Hs.83968 CD18 antigen -5.6 -1.6 ITPKB 203723_at Hs.78877 inositol 1,4,5-trisphosphate 3-kinase B -4.4

29 LASP1 200618_at Hs.334851 LIM and SH3 protein 1 -2.4 LBR 201795_at Hs.152931 lamin B receptor -5.4 -1.7 LENG4 211037_s_at Hs.78768 leukocyte receptor cluster (LRC) member 4 -4.1 LENG4 209179_s_at Hs.78768 leukocyte receptor cluster (LRC) member 4 -2.8 LENG5 218132_s_at Hs.15580 leukocyte receptor cluster (LRC) member 5 -3.9 LILRB2 210146_x_at Hs.22405 leukocyte Ig-like receptor -7.1 2.5 LILRB3 210225_x_at Hs.105928 leukocyte Ig-like receptor -2.9 3.4 LILRB3 210784_x_at Hs.105928 leukocyte Ig-like receptor -5.8 3.1 LILRB3 211135_x_at Hs.105928 leukocyte Ig-like receptor -3.8 1.5 2.3 LRP10 201412_at Hs.3804 low density lipoprotein receptor-related protein 10 -3.8 LRRN1 90610_at Hs.125742 leucine-rich repeat protein, neuronal 1 -2.2 LST1 214181_x_at Hs.380427 leukocyte specific transcript 1 -14.3 LST1 210629_x_at Hs.380427 leukocyte specific transcript 1 -4.9 LST1 215633_x_at Hs.380427 leukocyte specific transcript 1 -6.2 -1.5 LST1 214574_x_at Hs.380427 leukocyte specific transcript 1 -7.3 LST1 211582_x_at Hs.380427 leukocyte specific transcript 1 -10.2 LST1 211581_x_at Hs.380427 leukocyte specific transcript 1 -8.1 LY75 205668_at Hs.153563 lymphocyte antigen 75 -10.0 MAPK14 202530_at Hs.79107 MAP kinase 14 -15.8 MAPKAPK3 202788_at Hs.227789 MAP kinase-activated protein kinase 3 -3.3 MAPK1 208351_s_at Hs.324473 MAP kinase 1 -2.8 MAPK1 212271_at Hs.324473 MAP kinase 1 -2.1 MARK2 203942_s_at Hs.157199 MAP/microtubule affinity-regulating kinase 2 -44.9 MAP2K4 203266_s_at Hs.75217 MAP kinase kinase 4 -4.3 MAP3K2 221695_s_at Hs.28827 MAP kinase kinase kinase 2 -2.8 2.3 MAP3K5 203837_at Hs.151988 MAP kinase kinase kinase 5 -2.3 MAP3K5 203836_s_at Hs.151988 MAP kinase kinase kinase 5 -4.4 MCP 211574_s_at Hs.83532 membrane cofactor protein (CD46) -40.9 MCP 208783_s_at Hs.83532 membrane cofactor protein (CD46) -18.7 MCP 207549_x_at Hs.83532 membrane cofactor protein (CD46) -3.7 MEL 208819_at Hs.5947 mel transforming oncogene-RAB8 homolog -3.5 -1.5 MIR16 202593_s_at Hs.107014 membrane interacting protein of RGS16 -2.5 -2.0 MKNK2 218205_s_at Hs.261828 MAP kinase-interacting serine/threonine kinase 2 -4.8 MKPX 218845_at Hs.29106 mitogen-activated protein kinase phosphatase x -9.9 MLP 200644_at Hs.75061 MARCKS-like protein -2.3 MTMR1 213511_s_at Hs.347187 myotubularin related protein 1 -8.4 MTMR1 216095_x_at Hs.347187 myotubularin related protein 1 -2.4 MYD88 209124_at Hs.82116 myeloid differentiation primary response gene (88) -2.1 NRBP 217765_at Hs.272736 nuclear receptor binding protein -6.1 NMI 203964_at Hs.54483 N-myc (and STAT) interactor -3.5 2.0 NUDT3 221579_s_at Hs.4815 nudix-type motif 3 -4.1 PARK7 200006_at Hs.10958 Parkinson disease (autosomal recessive, early onset) 7 -2.3 PDLIM2 219165_at Hs.379109 PDZ and LIM domain 2 (mystique) -5.9 PELI1 218319_at Hs.7886 pellino homolog 1 (Drosophila) -6.2 2.2 PELI2 219132_at Hs.44038 pellino homolog 2 (Drosophila) -5.1 PIAS1 217862_at Hs.75251 protein inhibitor of activated STAT, 1 -2.9 PICALM 215832_x_at Hs.7885 phosphatidylinositol binding clathrin assembly protein -5.3 PICALM 212511_at Hs.7885 phosphatidylinositol binding clathrin assembly protein -3.4 PICALM 212506_at Hs.7885 phosphatidylinositol binding clathrin assembly protein -3.6

30 PICALM 215236_s_at Hs.90998 phosphatidylinositol binding clathrin assembly protein -24.5 2.6 1.8 1.5 PIK3CA 204369_at Hs.85701 phosphoinositide-3-kinase, catalytic, alpha polypeptide -3.2 PIK3CD 203879_at Hs.162808 phosphoinositide-3-kinase, catalytic, delta polypeptide -10.8 PIK3R4 212740_at Hs.83050 phosphoinositide-3-kinase, regulatory subunit 4, p150 -2.2 PILR(BETA) 220954_s_at Hs.349256 paired immunoglobulin-like receptor beta -8.5 PLCB2 204046_at Hs.355888 phospholipase C, beta 2 -5.9 PLCG2 204613_at Hs.75648 phospholipase C, gamma 2 (PI-specific) -3.3 PPM1A 203966_s_at Hs.57764 protein phosphatase 1A -4.7 PPM1B 209296_at Hs.5687 protein phosphatase 1B -2.4 PPM1F 203063_at Hs.278441 protein phosphatase 1F (PP2C domain containing) -8.1 -1.7 PPM1F 37384_at Hs.278441 protein phosphatase 1F (PP2C domain containing) -2.1 PPM1F 207758_at Hs.287732 protein phosphatase 1F (PP2C domain containing) -1.0 -2.0 PPP1CA 200846_s_at Hs.183994 protein phosphatase 1, catalytic subunit, alpha isoform -27.8 2.3 PPP1CB 201407_s_at Hs.21537 protein phosphatase 1, catalytic subunit, beta isoform -2.0 PPP1CC 200726_at Hs.79081 protein phosphatase 1, catalytic subunit, gamma isoform -9.6 PPP1R3D 204554_at Hs.42215 protein phosphatase 1, regulatory subunit 3D -5.2 PPP1R7 213465_s_at Hs.36587 protein phosphatase 1, regulatory subunit 7 -2.3 PPP1R12A 201602_s_at Hs.16533 protein phosphatase 1, reg. (inhibitor) subunit 12A -2.8 PPP1R12B 201957_at Hs.130760 protein phosphatase 1, reg. (inhibitor) subunit 12B -3.1 PPP2R5A 202187_s_at Hs.155079 protein phosphatase 2, regulatory subunit B -9.4 PPP3CA 202457_s_at Hs.272458 protein phosphatase 3 (formerly 2B), catalytic subunit -3.4 PPP3CA 202429_s_at Hs.272458 protein phosphatase 3 (formerly 2B), catalytic subunit -5.8 PPP4R1 201594_s_at Hs.3382 protein phosphatase 4, regulatory subunit 1 -2.7 PPP6C 206174_s_at Hs.356739 protein phosphatase 6, catalytic subunit -2.0 PPP6C 203529_at Hs.356739 protein phosphatase 6, catalytic subunit -3.9 2.3 PRC17 209403_at Hs.105891 Rab GTPase-activating protein PRC17 -6.6 PRKAR1A 200603_at Hs.183037 protein kinase, cAMP-dependent, regulatory, type I, α -3.9 PRKAR1A 200605_s_at Hs.183037 protein kinase, cAMP-dependent, regulatory, type I, α -4.8 PRKAR1A 200604_s_at Hs.183037 protein kinase, cAMP-dependent, regulatory, type I, α -5.1 PRKCB1 209685_s_at Hs.77202 protein kinase C, beta 1 -2.6 PRKCB1 207957_s_at Hs.77202 protein kinase C, beta 1 -4.0 PRKCL2 212629_s_at Hs.69171 protein kinase C-like 2 -2.4 -1.9 PRKCL2 212628_at Hs.432871 protein kinase C-like 2 -5.1 PRKD2 209282_at Hs.91146 protein kinase D2 -10.4 PRKWNK1 211992_at Hs.432900 protein kinase, lysine deficient 1 -10.3 PRKWNK1 211994_at Hs.432900 protein kinase, lysine deficient 1 -2.2 PSCDBP 209606_at Hs.270 pleckstrin homology domain binding protein -4.2 PTEN 204053_x_at Hs.10712 phosphatase and tensin homolog -6.4 PTEN 211711_s_at Hs.10712 phosphatase and tensin homolog -2.3 PTENP1 217492_s_at Hs.446477 phosphatase and tensin homolog, pseudogene 1 -4.0 PTP4A2 216988_s_at Hs.82911 protein tyrosine phosphatase type IVA, member 2 -5.9 PTP4A2 208615_s_at Hs.82911 protein tyrosine phosphatase type IVA, member 2 -2.0 -1.5 PTP4A2 208617_s_at Hs.82911 protein tyrosine phosphatase type IVA, member 2 -2.6 PTP4A2 208616_s_at Hs.82911 protein tyrosine phosphatase type IVA, member 2 -3.9 PTPRC 212588_at Hs.170121 protein tyrosine phosphatase, receptor type, C -2.3 PTPRC 207238_s_at Hs.170121 protein tyrosine phosphatase, receptor type, C -2.4 PTPRC 212587_s_at Hs.170121 protein tyrosine phosphatase, receptor type, C -2.7 PTPN6 206687_s_at Hs.63489 protein tyrosine phosphatase, non-receptor type 6 -3.8 P114-RHO-GEF 213039_at Hs.6150 Rho-specific guanine nucleotide exchange factor p114 -33.6

31 RAB2 208731_at Hs.78305 RAB2, member RAS oncogene family -6.4 RAB2 208734_x_at Hs.78305 RAB2, member RAS oncogene family -2.3 RAB3-GAP150 202373_s_at Hs.197289 rab3 GTPase-activating protein, non-catalytic subunit -2.2 RAB5C 201140_s_at Hs.479 RAB5C, member RAS oncogene family -2.3 RAB5C 201156_s_at Hs.479 RAB5C, member RAS oncogene family 1.1 1.8 RAB6C 210406_s_at Hs.333139 RAB6C, member RAS oncogene family -2.1 RAB14 200927_s_at Hs.5807 RAB14, member RAS oncogene family -5.0 RAB27A 209515_s_at Hs.50477 RAB27A, member RAS oncogene family -3.1 RAB31 217763_s_at Hs.223025 RAB31, member RAS oncogene family -4.6 RAB31 217764_s_at Hs.223025 RAB31, member RAS oncogene family -4.1 RAB31 217762_s_at Hs.223025 RAB31, member RAS oncogene family -3.0 RAC1 208641_s_at Hs.173737 Rac1 -4.3 RAC1 208640_at Hs.173737 Rac1 -2.4 RAF1 201244_s_at Hs.349650 v-raf-1 murine leukemia viral oncogene homolog 1 -2.9 RAPGEF2 203097_s_at Hs.154545 Rap guanine nucleotide exchange factor (GEF) 2 -3.3 RASA1 202677_at Hs.758 RAS p21 protein activator (GTPase activating protein) 1 -2.0 RASA1 210621_s_at Hs.758 RAS p21 protein activator (GTPase activating protein) 1 -1.2 -1.5 RASGRP2 208206_s_at Hs.99491 RAS guanyl releasing protein 2 -10.3 RASSF2 203185_at Hs.80905 Ras association (RalGDS/AF-6) domain family 2 -2.2 RCP 219681_s_at Hs.96125 Rab coupling protein -14.3 REPS2 205645_at Hs.80667 RALBP1 associated Eps domain containing 2 -9.0 RGS14 38290_at Hs.9347 regulator of G-protein signalling 14 -3.8 -1.7 RGS19 204336_s_at Hs.422336 regulator of G-protein signalling 19 -3.1 RIN3 219457_s_at Hs.180040 Ras and Rab interactor 3 -10.2 RIN3 60471_at Hs.180040 Ras and Rab interactor 3 -9.9 ROCK1 213044_at Hs.17820 Rho-associated, coiled-coil containing protein kinase 1 -3.6 RPGR 207624_s_at Hs.153614 retinitis pigmentosa GTPase regulator -2.8 SCAP2 204361_s_at Hs.52644 src family associated phosphoprotein 2 -3.4 SCAP2 204362_at Hs.52644 src family associated phosphoprotein 2 -7.5 SEPT6 212415_at Hs.90998 septin 6 -2.8 SH3GLB1 209091_s_at Hs.136309 SH3-domain GRB2-like endophilin B1 -2.8 SH3GLB1 210101_x_at Hs.136309 SH3-domain GRB2-like endophilin B1 -2.3 SH3BGRL3 221269_s_at Hs.109051 SH3 domain binding glutamic acid-rich protein like 3 -12.5 SH3BGRL 201311_s_at Hs.14368 SH3 domain binding glutamic acid-rich protein like -2.2 SH3BGRL 201312_s_at Hs.14368 SH3 domain binding glutamic acid-rich protein like -5.0 SIGLEC7 207224_s_at Hs.274470 sialic acid binding Ig-like lectin 7 -8.9 SKP1A 200718_s_at Hs.171626 S-phase kinase-associated protein 1A (p19A) -2.7 SKP1A 207974_s_at Hs.171626 S-phase kinase-associated protein 1A (p19A) -2.1 SNRK 209481_at Hs.79025 SNF-1 related kinase -5.4 SLA 203760_s_at Hs.75367 Src-like-adaptor -2.5 SRI 208921_s_at Hs.422340 sorcin -2.3 STAT1 209969_s_at Hs.21486 signal transducer and activator of transcription 1 -3.2 STAT3 208991_at Hs.381933 signal transducer and activator of transcription 3 -2.5 STAT5B 212549_at Hs.24064 signal transducer and activator of transcription 5B -2.1 STAT6 201332_s_at Hs.181015 signal transducer and activator of transcription 6 -2.8 STAT6 201331_s_at Hs.181015 signal transducer and activator of transcription 6 -4.5 STK4 211085_s_at Hs.35140 serine/threonine kinase 4 -10.9 STK24 208854_s_at Hs.168913 serine/threonine kinase 24 (STE20 homolog, yeast) -3.5 STK24 208855_s_at Hs.168913 serine/threonine kinase 24 (STE20 homolog, yeast) -4.1

32 STK17B 205214_at Hs.120996 serine/threonine kinase 17b (apoptosis-inducing) -2.1 STK38 202951_at Hs.8724 serine/threonine kinase 38 -2.9 STRN4 217903_at Hs.108665 striatin, calmodulin binding protein 4 -3.5 SYK 207540_s_at Hs.74101 spleen tyrosine kinase -46.0 SYK 209269_s_at Hs.351662 spleen tyrosine kinase -6.5 3.1 1.5 TBL1X 213400_s_at Hs.76536 transducin (beta)-like 1X-linked -29.0 TEBP 200627_at Hs.278270 unactive progesterone receptor, 23 kD -4.0 TGFBR2 208944_at Hs.82028 transforming growth factor, beta receptor II (70/80kDa) -8.6 TIP-1 209154_at Hs.12956 Tax interaction protein 1 -3.6 TLR4 221060_s_at Hs.159239 toll-like receptor 4 -2.9 1.5 TNFSF5IP1 218603_at Hs.6679 TNF superfamily, member 5-induced protein 1 -2.3 TNFSF5IP1 218467_at Hs.3726 TNF superfamily, member 5-induced protein 1 -2.2 TOB1 202704_at Hs.178137 transducer of ERBB2, 1 -2.3 TYK2 205546_s_at Hs.75516 tyrosine kinase 2 -12.7 TYROBP 204122_at Hs.9963 TYRO protein tyrosine kinase binding protein -2.9 TYR 3-monooxygenase/TRP 5-monooxygenase act. YWHAB 208743_s_at Hs.279920 protein -2.1 TYR 3-monooxygenase/TRP 5-monooxygenase act. YWHAB 217717_s_at Hs.182238 protein -3.1 TYR 3-monooxygenase/TRP 5-monooxygenase act. YWHAB 217718_s_at Hs.182238 protein -2.8

Apoptosis and cell fate Up-regulated (38) ARK5 204589_at Hs.200598 AMP-activated protein kinase family member 5 2.6 ASAH1 213902_at Hs.75811 N-acylsphingosine amidohydrolase (acid ceramidase) 1 2.5 BAG3 217911_s_at Hs.15259 BCL2-associated athanogene 3 2.7 BCL2A1 205681_at Hs.227817 BCL2-related protein A1 5.7 BRAF 206044_s_at Hs.622 v-raf murine sarcoma viral oncogene homolog B1 2.4 1.6 CCNE2 205034_at Hs.30464 cyclin E2 2.0 CDC2 203214_x_at Hs.334562 cell division cycle 2, G1 to S and G2 to M 2.5 CDC5L 209057_x_at Hs.155174 CDC5 cell division cycle 5-like (S. pombe) 4.4 -5.2 -1.6 -1.5 -1.7 CDC6 203967_at Hs.69563 CDC6 cell division cycle 6 homolog (S. cerevisiae) 2.3 -2.1 CDC27 214236_at Hs.442811 cell division cycle 27 2.2 CDK2 204252_at Hs.19192 cyclin-dependent kinase 2 3.1 CDKN1A 202284_s_at Hs.179665 cyclin-dependent kinase inhibitor 1A (p21, Cip1) 10.1 CHEK1 205394_at Hs.20295 CHK1 checkpoint homolog (S. pombe) 2.6 DNASE1L3 205554_s_at Hs.88646 deoxyribonuclease I-like 3 2.6 EDAR 220048_at Hs.58346 ectodysplasin 1, anhidrotic receptor 2.2 EI24 216396_s_at Hs.343911 etoposide induced 2.4 mRNA 2.1 GPNMB 201141_at Hs.82226 glycoprotein (transmembrane) nmb 2.0 -2.0 -3.1 GULP1 204237_at Hs.107056 GULP, engulfment adaptor PTB domain containing 1 2.7 JUN 213281_at Hs.78465 v-jun sarcoma virus 17 oncogene homolog (avian) 2.5 MAD2L1 203362_s_at Hs.79078 MAD2 mitotic arrest deficient-like 1 (yeast) 2.6 MLL 211826_s_at Hs.114765 myeloid/lymphoid or mixed-lineage leukemia 2.2 MORF4L2 201994_at Hs.173714 mortality factor 4 like 2 2.6 NCKAP1 217465_at Hs.278411 NCK-associated protein 1 2.0 -2.3 NEK1 216213_at Hs.48332 NIMA (never in mitosis gene a)-related kinase 1 2.1 NEK2 211080_s_at Hs.153704 NIMA (never in mitosis gene a)-related kinase 2 2.6 NEK3 211089_s_at Hs.2236 NIMA (never in mitosis gene a)-related kinase 3 2.3 -1.6 -2.1 NFKBIE 203927_at Hs.182885 NFKB inhibitor, epsilon 2.3

33 NFKB1 209239_at Hs.83428 NFKB1 (p105) 2.9 1.5 NR4A2 204622_x_at Hs.82120 nuclear receptor subfamily 4, group A, member 2 5.7 NR4A2 216248_s_at Hs.82120 nuclear receptor subfamily 4, group A, member 2 5.5 -2.3 PTN 209465_x_at Hs.44 pleiotrophin 4.4 -2.7 SHFM1 202276_at Hs.333495 split hand/foot malformation (ectrodactyly) type 1 3.3 SNCA 204467_s_at Hs.76930 synuclein, alpha 2.5 TIEG 202393_s_at Hs.82173 TGFB inducible early growth response 13.4 TNFRSF6B 206092_x_at Hs.348183 TNF receptor superfamily, member 6b, decoy 2.2 TNFSF9 206907_at Hs.1524 TNF (ligand) superfamily, member 9 3.2 TP73L 209863_s_at Hs.137569 tumor protein p73-like 2.1 TSPAN-3 200972_at Hs.100090 tetraspan 3 3.4 1.5 VDAC1 212038_s_at Hs.149155 voltage-dependent anion channel 1 2.0

Down-regulated (76) AIF1 215051_x_at Hs.76364 allograft inflammatory factor 1 -20.1 AIF1 209901_x_at Hs.76364 allograft inflammatory factor 1 -19.8 AIF1 213095_x_at Hs.76364 allograft inflammatory factor 1 -19.1 -1.7 AKT1 207163_s_at Hs.71816 v-akt murine thymoma viral oncogene homolog 1 -7.0 -1.9 APAF1 204859_s_at Hs.77579 apoptotic protease activating factor -2.2 APG4B 204903_x_at Hs.352535 APG4B: autophagin-1 -3.7 APG4B 212280_x_at Hs.352535 autophagin-1 -7.5 3.1 APG12L 213026_at Hs.264482 APG12 autophagy 12-like (S. cerevisiae) -2.0 ASC 221666_s_at Hs.71869 apoptosis-associated speck-like prot. contain. a CARD -11.8 BCAP31 200837_at Hs.291904 accessory protein BAP31 -3.4 2.2 BCL10 205263_at Hs.193516 B-cell CLL/lymphoma 10 -2.5 1.5 BTF 201084_s_at Hs.80338 Bcl-2-associated transcription factor -2.3 BTF 214499_s_at Hs.80338 Bcl-2-associated transcription factor 1.4 -1.7 BTG1 200920_s_at Hs.77054 B-cell translocation gene 1, anti-proliferative -4.6 -1.6 BTG1 200921_s_at Hs.77054 B-cell translocation gene 1, anti-proliferative -2.9 CABIN1 37652_at Hs.7840 calcineurin binding protein 1 -4.8 CASP3 202763_at Hs.74552 caspase 3, apoptosis-related cysteine protease -3.2 CASP8 213373_s_at Hs.381231 caspase 8, apoptosis-related cysteine protease -9.8 CCNG2 202769_at Hs.79069 cyclin G2 -7.2 -1.6 CCNG2 211559_s_at Hs.79069 cyclin G2 -2.7 CCNG2 202770_s_at Hs.79069 cyclin G2 -2.4 CCNI 208656_s_at Hs.79933 cyclin I -2.4 CCNI 208655_at Hs.79933 cyclin I -4.2 CDC2L1 207428_x_at Hs.214291 cell division cycle 2-like 1 (PITSLRE proteins) -14.5 CDC2L2 212401_s_at Hs.355896 cell division cycle 2-like 2 -3.2 CDC2L2 211289_x_at Hs.355896 cell division cycle 2-like 2 -8.6 CDC10 213151_s_at Hs.184326 CDC10 cell division cycle 10 homolog (S. cerevisiae) -3.0 CDC34 212540_at Hs.423615 cell division cycle 34 -4.5 -1.5 CDKN1B 209112_at Hs.238990 cyclin-dependent kinase inhibitor 1B (p27, Kip1) -5.6 CDK5RAP3 218740_s_at Hs.20157 CDK5 regulatory subunit associated protein 3 -2.3 CFLAR 208485_x_at Hs.195175 CASP8 and FADD-like apoptosis regulator -2.6 CFLAR 210563_x_at Hs.195175 CASP8 and FADD-like apoptosis regulator 1.4 1.6 1.7 1.8 CFLAR 209939_x_at Hs.195175 CASP8 and FADD-like apoptosis regulator 1.8 1.6 1.9 CHFR 218803_at Hs.23794 checkpoint with forkhead and ring finger domains -2.1 CLK1 210346_s_at Hs.406557 CDC-like kinase 1 -2.1

34 CLK1 214683_s_at Hs.2083 CDC-like kinase 1 -5.2 CTBP2 201218_at Hs.171391 C-terminal binding protein 2 -2.5 1.5 DEK 200934_at Hs.110713 DEK oncogene (DNA binding) -5.4 FNBP1 212288_at Hs.301763 formin binding protein 1 -3.6 FNBP1 213940_s_at Hs.301763 formin binding protein 1 -7.5 2.7 FNBP3 218053_at Hs.107213 formin binding protein 3 -5.1 FOXO1A 202724_s_at Hs.170133 forkhead box O1A (rhabdomyosarcoma) -2.3 2.1 GADD45G 204121_at Hs.9701 growth arrest and DNA-damage-inducible, gamma -5.0 HSMPP8 221771_s_at Hs.244482 M-phase phosphoprotein, mpp8 -13.8 KHDRBS1 200040_at Hs.119537 KH domain-containing, RNA binding protein -2.0 IRF1 202531_at Hs.80645 interferon regulatory factor 1 -2.4 1.7 2.2 IRF3 202621_at Hs.75254 interferon regulatory factor 3 -37.8 3.8 IKBKG 209929_s_at Hs.43505 IKB, kinase gamma -14.4 1.7 3.0 JTB 200048_s_at Hs.6396 jumping translocation breakpoint -3.1 JTB 210927_x_at Hs.6396 jumping translocation breakpoint -2.1 JWA 200761_s_at Hs.92384 vitamin A responsive; cytoskeleton related -7.8 JWA 200760_s_at Hs.92384 vitamin A responsive; cytoskeleton related -6.3 LASS2 222212_s_at Hs.285976 LAG1 longevity assurance homolog 2 (S. cerevisiae) -3.6 LMO2 204249_s_at Hs.184585 LIM domain only 2 (rhombotin-like 1) -2.5 MADH2 203077_s_at Hs.82483 MAD, mothers against decapentaplegic homolog 2 -11.9 MADH2 203076_s_at Hs.380719 MAD, mothers against decapentaplegic homolog 2 -2.2 MAX 208403_x_at Hs.42712 MAX protein -11.4 MAX 209332_s_at Hs.42712 MAX protein -2.8 MAX 209331_s_at Hs.42712 MAX protein -4.4 MAX 210734_x_at Hs.42712 MAX protein -20.8 2.5 MCL1 200797_s_at Hs.86386 myeloid cell leukemia sequence 1 (BCL2-related) -2.6 MCL1 200798_x_at Hs.86386 myeloid cell leukemia sequence 1 (BCL2-related) -2.8 MCL1 214057_at Hs.86386 myeloid cell leukemia sequence 1 (BCL2-related) -1.2 -1.7 1.5 MFNG 204152_s_at Hs.31939 manic fringe homolog (Drosophila) -6.4 MFNG 204153_s_at Hs.31939 manic fringe homolog (Drosophila) -3.7 MLLT2 201924_at Hs.114765 myeloid/lymphoid or mixed-lineage leukemia -2.7 MST4 218499_at Hs.23643 Mst3 and SOK1-related kinase -2.2 MXI1 202364_at Hs.118630 MAX interacting protein 1 -2.0 NALP1 210113_s_at Hs.104305 CARD7, DEFCAP, PP1044 -38.0 NALP1 218380_at Hs.7212 CARD7, DEFCAP, PP1044 -11.2 NALP1 211822_s_at Hs.104305 CARD7, DEFCAP, PP1044 -6.5 NALP1 211824_x_at Hs.104305 CARD7, DEFCAP, PP1044 -4.9 NEK7 212530_at Hs.24119 NIMA (never in mitosis gene a)-related kinase 7 -5.6 NOTCH1 218902_at Hs.129053 Notch homolog 1, translocation-associated (Drosophila) -6.4 NOTCH2 212377_s_at Hs.8121 Notch homolog 2 (Drosophila) -2.3 NR3C1 211671_s_at Hs.75772 glucocorticoid receptor -2.1 NR3C1 216321_s_at Hs.75772 glucocorticoid receptor -2.6 OS4 203445_s_at Hs.355816 conserved gene amplified in osteosarcoma -4.1 OS-9 200714_x_at Hs.76228 amplified in osteosarcoma -3.3 PAK2 208877_at Hs.284275 p21 (CDKN1A)-activated kinase 2 -3.8 PAK2 208878_s_at Hs.284275 p21 (CDKN1A)-activated kinase 2 -2.2 PAK2 208875_s_at Hs.284275 p21 (CDKN1A)-activated kinase 2 -3.0 PDCD4 202730_s_at Hs.326248 programmed cell death 4 -2.0 PDCD4 212593_s_at Hs.326248 programmed cell death 4 -8.2

35 PDCD4 212594_at Hs.422407 programmed cell death 4 -3.6 PDCD6 203415_at Hs.80019 programmed cell death 6 -5.0 PDCD10 210907_s_at Hs.28866 programmed cell death 10 -3.0 PELO 218472_s_at Hs.5798 pelota homolog (Drosophila) -2.8 PLAGL1 207002_s_at Hs.75825 pleiomorphic adenoma gene-like 1 -4.3 PLAGL1 207943_x_at Hs.75825 pleiomorphic adenoma gene-like 1 -2.1 PLAGL1 209318_x_at Hs.75825 pleiomorphic adenoma gene-like 1 -2.1 PORIMIN 211967_at Hs.172089 pro-oncosis receptor inducing membrane injury gene -2.5 PRSS25 211152_s_at Hs.115721 protease, serine, 25 -2.8 REQ 202116_at Hs.13495 requiem, apoptosis response zinc finger gene -11.5 SON 201086_x_at Hs.92909 SON DNA binding protein -2.9 STAG2 209023_s_at Hs.8217 stromal antigen 2 -4.3 STAG2 207983_s_at Hs.8217 stromal antigen 2 -3.8 STAG2 209022_at Hs.8217 stromal antigen 2 -2.8 TAX1BP1 200976_s_at Hs.5437 Tax1 binding protein 1 -2.8 TAX1BP1 200977_s_at Hs.5437 Tax1 binding protein 1 -2.4 TEGT 200804_at Hs.74637 testis enhanced gene transcript (BAX inhibitor 1) -2.6 TLE4 204872_at Hs.99824 transducin-like enhancer of split 4 -3.5 TNFRSF10B 209295_at Hs.51233 TNF receptor superfamily, member 10b -7.3 2.1 TNFRSF10C 211163_s_at Hs.119684 TNF receptor superfamily, member 10c, decoy -32.1 -1.9 TNFRSF10C 206222_at Hs.119684 TNF receptor superfamily, member 10c, decoy -12.9 -1.5 TNFRSF1A 207643_s_at Hs.159 TNF receptor superfamily, member 1A -5.1 -1.8 TNFRSF6 216252_x_at Hs.82359 CD95, TNF receptor superfamily, member 6 -2.9 TNFRSF6 204780_s_at Hs.82359 CD95, TNF receptor superfamily, member 6 -2.7 2.2 TNFRSF6 215719_x_at Hs.82359 CD95, TNF receptor superfamily, member 6 -3.1 1.6 1.6 1.5 2.0 TNFSF10 202688_at Hs.83429 TNF (ligand) superfamily, member 10 -4.8 TNFSF10 202687_s_at Hs.83429 TNF (ligand) superfamily, member 10 -8.9 TP53BPL 204071_s_at Hs.179982 tumor protein p53-binding protein -3.9 TRADD 1729_at Hs.89862 TNFRSF1A-associated via death domain -3.4 TRIAD3 218425_at Hs.86228 TRIAD3 protein -6.1 TUCAN 204950_at Hs.10031 tumor up-regulated CARD-cont. antagonist of casp 9 -2.5

Transcription and DNA binding Up-regulated (83) APP 214953_s_at Hs.177486 amyloid beta (A4) precursor protein 2.0 ARID4B 214139_at Hs.17428 AT rich interactive domain 4B (RBP1- like) 2.3 ASH1L 218554_s_at Hs.102652 ash1 (absent, small, or homeotic)-like (Drosophila) 2.1 ATF7 206684_s_at Hs.55888 activating transcription factor 7 2.1 A2BP1 221217_s_at Hs.57937 ataxin 2-binding protein 1 2.8 BHLHB2 201170_s_at Hs.171825 basic helix-loop-helix domain containing, class B, 2 2.7 CCRN4L 220671_at Hs.258586 CCR4 carbon catabolite repression 4-like (S. cerevisiae) 2.1 CLOCK 217563_at Hs.438738 clock homolog (mouse) 2.2 CROC4 222301_at Hs.281145 transcriptional activator of the c-fos promoter 3.5 DDX10 204977_at Hs.41706 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 10 2.3 DDX18 205763_s_at Hs.100555 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 18 2.3 DDX32 218198_at Hs.171835 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 32 2.2 DDX52 210320_s_at Hs.380430 DEAD (Asp-Glu-Ala-Asp) box polypeptide 52 2.1 DHX29 212649_at Hs.95665 DEAH (Asp-Glu-Ala-His) box polypeptide 29 2.2 DMC1 208382_s_at Hs.37181 dosage suppressor of mck1 homolog 2.4

36 DPF3 219746_at Hs.192922 D4, zinc and double PHD fingers, family 3 2.1 DUT 208955_at Hs.367676 dUTP pyrophosphatase 2.2 ENO1 201231_s_at Hs.254105 enolase 1, (alpha) 2.3 E2F1 2028_s_at Hs.96055 E2F transcription factor 1 2.0 FOXF2 206377_at Hs.44481 forkhead box F2 2.1 GATA2 209710_at Hs.760 GATA binding protein 2 2.0 -2.0 -1.8 -2.1 GCN5L2 202182_at Hs.101067 GCN5 general control of amino-acid synthesis 5-like 2 2.3 G3BP 222187_x_at Ras-GAP SH3-domain-binding protein 2.7 -3.5 -1.8 HES1 203395_s_at Hs.250666 hairy and enhancer of split 1, (Drosophila) 2.3 HIST1H4H 208181_at Hs.421737 histone 1, H4h 2.6 HMGB3 203744_at Hs.19114 high-mobility group box 3 2.0 HOXB5 205600_x_at Hs.22554 homeo box B5 2.5 HOXB5 205601_s_at Hs.22554 homeo box B5 4.7 HOXB7 216973_s_at Hs.819 homeo box B7 2.3 -2.0 HOXC10 218959_at Hs.44276 homeo box C10 2.3 H2AFY 220375_s_at Hs.75258 H2A histone family, member Y 2.7 IMP-3 203820_s_at Hs.79440 IGF-II mRNA-binding protein 3 2.4 L3MBTL 213837_at Hs.300863 l(3)mbt-like (Drosophila) 2.5 MAFG 204970_s_at Hs.252229 v-maf oncogene homolog G (avian) 4.3 MBD5 220195_at Hs.94125 methyl-CpG binding domain protein 5 2.2 MEIS2 207480_s_at Hs.104105 myeloid ecotropic viral integration site 1 homolog 2 2.4 1.6 MJD 205416_s_at Hs.66521 Machado-Joseph disease (ataxin 3) 2.4 MTSG1 212096_s_at Hs.7946 mitochondrial tumor suppressor gene 1 2.6 MYNN 218926_at Hs.22934 myoneurin 2.1 NASP 201969_at Hs.380400 nuclear autoantigenic sperm protein (histone-binding) 2.1 NHLH2 215228_at Hs.46296 nescient helix loop helix 2 2.2 NOLC1 205895_s_at Hs.75337 nucleolar and coiled-body phosphoprotein 1 2.2 NOL5A 200874_s_at Hs.296585 nucleolar protein 5A (56kDa with KKE/D repeat) 2.1 NP 201695_s_at Hs.75514 nucleoside phosphorylase 2.9 NPAS2 39548_at Hs.321164 neuronal PAS domain protein 2 2.8 PEG3 209242_at Hs.139033 paternally expressed 3 2.4 PMX1 205991_s_at Hs.443452 paired mesoderm homeo box 1 2.6 POLR3F 205218_at Hs.128207 polymerase (RNA) III (DNA directed) polypeptide F 2.5 POU4F1 206940_s_at Hs.211588 POU domain, class 4, transcription factor 1 2.7 POU4F2 207725_at Hs.266 POU domain, class 4, transcription factor 2 2.6 REL 206035_at Hs.44313 v-rel reticuloendotheliosis viral oncogene hom. (avian) 2.1 1.5 RLF 204243_at Hs.13321 rearranged L-myc fusion sequence 3.0 RNF18 221154_at Hs.283103 ring finger protein 18 2.7 RNGTT 211387_x_at Hs.27345 RNA guanylyltransferase and 5'-phosphatase 2.3 -2.0 RNMT 202683_s_at Hs.8086 RNA (guanine-7-) methyltransferase 2.0 R3HDM 202754_at Hs.268053 R3H domain. containing 2.2 SBNO1 218737_at Hs.380419 sno, strawberry notch homolog 1 (Drosophila) 2.0 SFRS3 208672_s_at Hs.388623 splicing factor, arginine/serine-rich 3 2.0 SIP1 211115_x_at Hs.102456 survival of motor neuron protein interacting protein 1 2.6 SIX2 206511_s_at Hs.101937 sine oculis homeobox homolog 2 (Drosophila) 2.4 SIX6 207250_at Hs.194756 sine oculis homeobox homolog 6 (Drosophila) 2.1 SMARCA1 203874_s_at Hs.152292 actin dependent regulator of chromatin 2.8 1.7 SMARCA2 212257_s_at Hs.198296 actin dependent regulator of chromatin 2.1 SMARCA3 202983_at Hs.3068 actin dependent regulator of chromatin 2.0

37 SNAPC1 205443_at Hs.179312 small nuclear RNA activating complex, polypeptide 1 14.1 2.0 SOX2 214178_s_at Hs.816 SRY (sex determining region Y)-box 2 2.4 SYCP1 216917_s_at Hs.112743 synaptonemal complex protein 1 2.1 SYCP2 206546_at Hs.202676 synaptonemal complex protein 2 2.8 TAF6L 213209_at Hs.131846 TAF6-like RNA pol. II-assoc. factor-associated factor 2.2 TCF7L1 221016_s_at Hs.102367 transcription factor 7-like 1 (T-cell specific, HMG-box) 2.5 TCF20 215511_at Hs.201668 transcription factor 20 (AR1) 2.1 TCF20 212931_at Hs.201668 transcription factor 20 (AR1) -3.7 2.1 TFAM 203177_x_at Hs.75133 transcription factor A, mitochondrial 2.1 -1.5 -1.5 -2.2 TFDP1 204147_s_at Hs.79353 transcription factor Dp-1 2.5 TFDP1 212330_at Hs.79353 transcription factor Dp-1 2.6 TNRC4 215045_at Hs.26047 trinucleotide repeat containing 4 3.2 TOX 204529_s_at Hs.184297 thymus high mobility group box protein TOX 2.0 TRIM10 210579_s_at Hs.274295 tripartite motif-containing 10 2.4 TRIM45 219923_at Hs.301526 tripartite motif-containing 45 2.3 ZFD25 205739_x_at Hs.50216 zinc finger protein (ZFD25) 3.1 ZFP36 201531_at Hs.343586 zinc finger protein 36, C3H type, homolog (mouse) 2.7 ZNFN1A4 208472_at Hs.302031 zinc finger protein, subfamily 1A, 4 (Eos) 2.6 ZNF43 206695_x_at Hs.74107 zinc finger protein 43 (HTF6) 2.4 ZNF239 206261_at Hs.25040 zinc finger protein 239 2.5 ZNF239 206261_at Hs.25040 zinc finger protein 239 2.5 -2.0 ZNF292 212366_at Hs.173081 zinc finger protein 292 2.5 ZNF339 211778_s_at Hs.71935 zinc finger protein 339 2.2 ZNF365 206448_at Hs.22653 zinc finger protein 365 2.6

Down-regulated (185) ADAR 201786_s_at Hs.7957 adenosine deaminase, RNA-specific -2.3 ADNP 201773_at Hs.3657 activity-dependent neuroprotector -3.0 APOBEC3A 210873_x_at Hs.348983 apolipoprotein B mRNA editing enzyme-like 3A -6.8 ARNTL 209824_s_at Hs.74515 aryl hydrocarbon receptor nuclear translocator-like -7.7 ARNTL 210971_s_at Hs.74515 aryl hydrocarbon receptor nuclear translocator-like -7.4 AXOT 202653_s_at Hs.5306 axotrophin -4.8 BAZ2A 201353_s_at Hs.277401 bromodomain adjacent to zinc finger domain, 2A -2.1 BAZ2B 203080_s_at Hs.8383 bromodomain adjacent to zinc finger domain, 2B -5.1 BCOR 219433_at Hs.130732 BCL-6 interacting corepressor -7.9 2.4 BRD4 202102_s_at Hs.278675 bromodomain containing 4 -2.2 BRD7 221776_s_at Hs.279762 bromodomain containing 7 -3.7 BRD8 202227_s_at Hs.5464 bromodomain containing 8 -3.5 -1.5 CAMTA2 212948_at Hs.107362 calmodulin binding transcription activator 2 -2.2 CBX3 200037_s_at Hs.406384 chromobox homolog 3 -2.9 CBX7 212914_at Hs.152151 chromobox homolog 7 -17.8 -1.7 CENTB2 212476_at Hs.24340 centaurin, beta 2 -3.0 CNOT2 222182_s_at Hs.239720 CCR4-NOT transcription complex, subunit 2 -2.2 COPEB 208961_s_at Hs.285313 core promoter element binding protein -7.4 2.4 CREBBP 202160_at Hs.23598 CREB binding protein (Rubinstein-Taybi syndrome) -2.3 CREB1 204312_x_at Hs.79194 cAMP responsive element binding protein 1 -3.5 CREB1 204313_s_at Hs.79194 cAMP responsive element binding protein 1 -2.1 1.5 CREB1 204314_s_at Hs.79194 cAMP responsive element binding protein 1 -4.2 CTCF 202521_at Hs.57419 CCCTC-binding factor (zinc finger protein) -10.9

38 CUGBP2 202156_s_at Hs.211610 CUG triplet repeat, RNA binding protein 2, NAPOR -12.3 CUGBP2 202158_s_at Hs.211610 CUG triplet repeat, RNA binding protein 2, NAPOR -3.8 -1.6 CUGBP2 202157_s_at Hs.211610 CUG triplet repeat, RNA binding protein 2, NAPOR -5.3 CUL4B 202214_s_at Hs.155976 cullin 4B -15.5 CUL3 201371_s_at Hs.78946 cullin 3 -3.2 DCP2 212919_at Hs.396470 decapping enzyme hDcp2 -4.7 DDX3 212515_s_at Hs.380774 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3 -3.6 DDX15 201385_at Hs.5683 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 15 -6.4 DDX16 203694_s_at Hs.12797 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 16 -2.2 DHX40 218277_s_at Hs.29403 DEAH (Asp-Glu-Ala-His) box polypeptide 40 -2.2 DICER1 213229_at Hs.87889 Dicer1, Dcr-1 homolog (Drosophila) -11.4 DICER1 206061_s_at Hs.87889 Dicer1, Dcr-1 homolog (Drosophila) -4.5 DICER1 212188_at Hs.109438 Dicer1, Dcr-1 homolog -7.7 -1.8 DR1 209187_at Hs.16697 down-regulator of transcription 1, TBP-binding -4.3 DSIPI 207001_x_at Hs.75450 delta sleep inducing peptide, immunoreactor -8.8 -1.8 DSIPI 208763_s_at Hs.75450 delta sleep inducing peptide, immunoreactor -6.1 -1.7 ELF4 31845_at Hs.151139 E74-like factor 4 (ets domain transcription factor) -2.5 EP300 202221_s_at Hs.25272 E1A binding protein p300 -2.7 EWSR1 211825_s_at Ewing sarcoma breakpoint region 1 -5.4 EZH1 32259_at Hs.194669 enhancer of zeste homolog 1 (Drosophila) -3.5 EZH1 203249_at Hs.194669 enhancer of zeste homolog 1 (Drosophila) -16.7 4.4 E1B-AP5 209675_s_at Hs.155218 E1B-55kDa-associated protein 5 -9.0 E1B-AP5 208713_at Hs.155218 E1B-55kDa-associated protein 5 -1.3 -1.6 FMR1 215245_x_at Hs.89764 fragile X mental retardation 1 -2.9 FMR1 203689_s_at Hs.89764 fragile X mental retardation 1 -2.2 GTF2I 201065_s_at Hs.278589 general transcription factor II, i -39.0 GTF2I 210891_s_at Hs.278589 general transcription factor II, i -16.7 GTF3A 215091_s_at Hs.75113 general transcription factor IIIA -3.0 G22P1 200792_at Hs.197345 thyroid autoantigen 70kDa (Ku antigen) -2.2 HCLS1 202957_at Hs.14601 hematopoietic cell-specific Lyn substrate 1 -2.7 HELSNF1 212571_at Hs.173421 helicase with SNF2 domain 1 -5.3 HIPK1 212293_at Hs.12259 homeodomain interacting protein kinase 1 -2.2 HIPK1 212291_at Hs.12259 homeodomain interacting protein kinase 1 -6.5 2.0 HIST1H2AC 215071_s_at Hs.28777 histone 1, H2ac -8.2 HIST1H2BC 214455_at Hs.356901 histone 1, H2bc -3.1 HIST1H2BK 208579_x_at Hs.247817 histone 1, H2bk -7.7 -1.6 HIST1H2BK 209806_at Hs.247817 histone 1, H2bk -8.0 2.6 HIST1H3D 214472_at Hs.143042 histone 1, H3d -3.3 HIST2H2AA 218280_x_at Hs.417332 histone 2, H2aa -2.5 HLX1 214438_at Hs.74870 H2.0-like homeo box 1 (Drosophila) -3.7 H2AFY 207168_s_at Hs.75258 H2A histone family, member Y -2.5 H2AFZ 213911_s_at Hs.119192 H2A histone family, member Z -5.8 H2AFZ 200853_at Hs.119192 H2A histone family, member Z -2.6 HMGB1 200680_x_at Hs.6727 high-mobility group box 1 -2.2 HMGB1 214938_x_at Hs.6727 high-mobility group box 1 -3.0 HMGB2 208808_s_at Hs.80684 high-mobility group box 2 -6.6 HMGN1 200943_at Hs.251064 high-mobility group nucleosome binding domain 1 -3.9 -1.6 HMGN1 200944_s_at Hs.251064 high-mobility group nucleosome binding domain 1 -2.6 HMGN2 208668_x_at Hs.181163 high-mobility group nucleosomal binding domain 2 -2.2

39 HMGN4 209786_at Hs.236774 high mobility group nucleosomal binding domain 4 -3.6 HMGN4 209787_s_at Hs.236774 high mobility group nucleosomal binding domain 4 -4.2 HNRPD 213359_at Hs.378751 heterogeneous nuclear ribonucleoprotein D -2.6 HNRPH3 208990_s_at Hs.279681 heterogeneous nuclear ribonucleoprotein H3 (2H9) -3.4 HNRPK 200097_s_at Hs.129548 heterogeneous nuclear ribonucleoprotein K -2.6 HNRPK 200775_s_at Hs.129548 heterogeneous nuclear ribonucleoprotein K -3.9 HPIP 212259_s_at Hs.8068 hematopoietic PBX-interacting protein -12.8 -1.5 HPIP 214177_s_at Hs.8068 hematopoietic PBX-interacting protein -3.2 -1.7 HPIP 214176_s_at Hs.8068 hematopoietic PBX-interacting protein -4.6 HPRP3P 202251_at Hs.11776 U4/U6-associated RNA splicing factor -4.1 HSBP1 200942_s_at Hs.250899 heat shock factor binding protein 1 -3.5 HTATIP2 209448_at Hs.90753 HIV-1 Tat interactive protein 2, 30kDa -5.1 H1FX 204805_s_at Hs.75307 H1 histone family, member X -17.6 2.1 2.6 H2AV 202487_s_at Hs.301005 histone H2A.F/Z variant -3.9 2.5 ID2 213931_at Hs.180919 inhibitor of DNA binding 2 -4.1 ID2 201565_s_at Hs.180919 inhibitor of DNA binding 2 3.0 JJAZ1 212287_at Hs.197803 joined to JAZF1 -2.4 LKAP 202386_s_at Hs.432741 limkain b1 -7.4 LRRFIP1 201862_s_at Hs.326159 leucine rich repeat (in FLII) interacting protein 1 -5.5 LRRFIP1 211452_x_at Hs.326159 leucine rich repeat (in FLII) interacting protein 1 -2.8 LUC7A 208835_s_at Hs.3688 cisplatin resistance-associated overexpressed protein -5.4 LUC7A 220044_x_at Hs.3688 cisplatin resistance-associated overexpressed protein -3.1 MATR3 214363_s_at Hs.78825 matrin 3 -2.9 MATR3 200626_s_at Hs.78825 matrin 3 -2.5 MATR3 200624_s_at Hs.78825 matrin 3 -1.0 -1.5 MBD2 202484_s_at Hs.25674 methyl-CpG binding domain protein 2 -4.7 MBD4 214047_s_at Hs.35947 methyl-CpG binding domain protein 4 -38.2 MBD4 209580_s_at Hs.35947 methyl-CpG binding domain protein 4 -11.9 MBD4 209579_s_at Hs.35947 methyl-CpG binding domain protein 4 -6.4 -1.6 MBNL1 201153_s_at Hs.28578 muscleblind-like (Drosophila) -7.6 MBNL1 201152_s_at Hs.28578 muscleblind-like (Drosophila) -6.7 MEF2C 209199_s_at Hs.78995 MADS box transcription enhancer factor 2, C -4.5 MYOD1 206656_s_at Hs.22391 myogenic factor 3 -3.6 MYT1 212406_s_at Hs.279562 myelin transcription factor 1 -3.6 NCOA1 210249_s_at Hs.74002 nuclear receptor coactivator 1 -3.2 NCOA1 209105_at Hs.74002 nuclear receptor coactivator 1 -15.5 2.7 NCOA1 209106_at Hs.74002 nuclear receptor coactivator 1 -9.7 3.7 NCOA1 209107_x_at Hs.74002 nuclear receptor coactivator 1 -2.9 2.0 NCOA2 212867_at Hs.404048 nuclear receptor coactivator 2 -5.1 NCOA4 210774_s_at Hs.99908 nuclear receptor coactivator 4 -4.9 NDE1 218414_s_at Hs.263925 nudE nuclear distribution gene E homolog 1 -5.9 NFE2 209930_s_at Hs.75643 nuclear factor (erythroid-derived 2), 45kDa -23.4 NLI-IF 217844_at Hs.283724 nuclear LIM interactor-interacting factor -5.8 NONO 208698_s_at Hs.172207 non-POU domain containing, octamer-binding -4.0 NP220 213775_x_at Hs.169984 NP220 nuclear protein -3.5 NRBF-2 221803_s_at Hs.27181 nuclear receptor binding factor-2 -3.9 NFYC 211797_s_at Hs.168157 nuclear transcription factor Y, gamma -10.5 3.4 PAM 201960_s_at Hs.151411 protein associated with Myc -4.9 PAPOLA 222035_s_at Hs.49007 poly(A) polymerase alpha -3.6

40 PC4 214512_s_at Hs.349506 activated RNA polymerase II transcription cofactor 4 -2.4 PHF2 212726_at Hs.93868 PHD finger protein 2 -3.9 PHF3 217954_s_at Hs.78893 PHD finger protein 3 -2.9 PILB 218773_s_at Hs.419780 pilin-like transcription factor -4.1 -1.8 PJA2 201133_s_at Hs.279849 praja 2, RING-H2 motif containing -2.9 PNN 212036_s_at Hs.44499 pinin, desmosome associated protein -7.7 POLB 203616_at Hs.180107 polymerase (DNA directed), beta -4.8 POLR2B 201803_at Hs.296014 polymerase (RNA) II (DNA directed) polypeptide B -2.5 POLR2E 217854_s_at Hs.24301 polymerase (RNA) II (DNA directed) polypeptide E -10.8 POLR2E 213887_s_at Hs.24301 polymerase (RNA) II (DNA directed) polypeptide E -2.3 POLR2J 212782_x_at Hs.220255 polymerase (RNA) II (DNA directed) polypeptide J -15.3 3.2 PFDN5 210908_s_at Hs.288856 prefoldin 5 -2.9 PFDN5 207132_x_at Hs.288856 prefoldin 5 -2.1 PHF3 217952_x_at Hs.78893 PHD finger protein 3 -2.1 PRPF8 200000_s_at Hs.181368 PRP8 pre-mRNA processing factor 8 homolog (yeast) -12.7 PSIP2 209337_at Hs.82110 PC4 and SFRS1 interacting protein 2 -2.7 PTBP1 202189_x_at Hs.172550 polypyrimidine tract binding protein 1 -5.9 PTBP1 211270_x_at Hs.172550 polypyrimidine tract binding protein 1 -5.5 PTBP1 216306_x_at Hs.172550 polypyrimidine tract binding protein 1 -2.3 RAD23B 201222_s_at Hs.404283 RAD23 homolog B (S. cerevisiae) -2.5 1.7 RALY 201271_s_at Hs.74111 RNA binding protein -10.4 2.5 RBBP2 202040_s_at Hs.76272 retinoblastoma binding protein 2 -3.5 RBL2 212331_at Hs.79362 retinoblastoma-like 2 (p130) -3.7 RBMS1 209868_s_at Hs.241567 RNA binding motif, single stranded interacting prot. 1 -2.8 RBMS1 215127_s_at Hs.241567 RNA binding motif, single stranded interacting prot. 1 -3.7 RBMS1 203748_x_at Hs.241567 RNA binding motif, single stranded interacting prot. 1 -7.8 1.5 2.1 RBMS1 207266_x_at Hs.241567 RNA binding motif, single stranded interacting prot. 1 -10.9 2.1 RBM5 201394_s_at Hs.201675 RNA binding motif protein 5 -3.4 RBM5 201395_at Hs.201675 RNA binding motif protein 5 -4.5 RBPSUH 207785_s_at Hs.347340 recombining binding protein suppressor of hairless -4.2 RBPSUH 211974_x_at Hs.356806 recombining binding protein suppressor of hairless -2.7 RCOR 212612_at Hs.78398 REST corepressor -5.3 RFP 212116_at Hs.142653 ret finger protein -3.3 RIG-I 218943_s_at Hs.145612 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide -3.3 ROD1 214697_s_at Hs.374634 ROD1 regulator of differentiation 1 (S. pombe) -2.0 RNF4 212696_s_at Hs.66394 ring finger protein 4 -8.1 RNF6 203403_s_at Hs.32597 ring finger protein (C3H2C3 type) 6 -6.8 RNF38 218528_s_at Hs.77823 ring finger protein 38 -3.1 RNF44 203286_at Hs.179946 ring finger protein 44 -3.4 RNF138 218738_s_at Hs.180403 ring finger protein 138 -3.0 RNPC2 207941_s_at Hs.145696 RNA-binding region (RNP1, RRM) containing 2 -2.3 RNPC7 212033_at Hs.180789 RNA-binding region (RNP1, RRM) containing 7 -2.1 RNPS1 200060_s_at Hs.75104 RNA binding protein S1, serine-rich domain -2.5 RUNX3 204198_s_at Hs.170019 runt-related transcription factor 3 -2.5 SAP18 208742_s_at Hs.23964 sin3-associated polypeptide, 18kDa -2.3 SATB1 203408_s_at Hs.74592 special AT-rich sequence binding protein 1 -2.0 SET 200631_s_at Hs.145279 SET translocation (myeloid leukemia-associated) -9.8 SET 40189_at Hs.145279 SET translocation (myeloid leukemia-associated) -9.3 SET 213047_x_at Hs.145279 SET translocation (myeloid leukemia-associated) -2.2

41 SET 213048_s_at Hs.145279 SET translocation (myeloid leukemia-associated) -3.7 SBF1 39835_at Hs.112049 SET binding factor 1 -3.4 SFPQ 214016_s_at Hs.180610 splicing factor proline/glutamine rich -4.9 SFPQ 221768_at Hs.433517 splicing factor proline/glutamine rich -2.1 2.6 SFRS4 201696_at Hs.76122 splicing factor, arginine/serine-rich 4 -2.3 SFRS7 213649_at Hs.184167 splicing factor, arginine/serine-rich 7, 35kDa -2.8 SFRS7 214141_x_at Hs.184167 splicing factor, arginine/serine-rich 7, 35kDa -2.3 3.4 SFRS9 200044_at Hs.77608 splicing factor, arginine/serine-rich 9 -4.5 SFRS11 200686_s_at Hs.433581 splicing factor, arginine/serine-rich 11 -2.5 SFRS11 213742_at Hs.433581 splicing factor, arginine/serine-rich 11 1.2 -1.5 SFRS2IP 206989_s_at Hs.51957 splicing factor, arginine/serine-rich 2, interacting protein -3.1 SF1 208313_s_at Hs.180677 splicing factor 1 -2.3 SF3A1 201356_at Hs.406277 splicing factor 3a, subunit 1, 120kDa -2.1 SF3B1 201071_x_at Hs.334826 splicing factor 3b, subunit 1, 155kDa -3.0 SHAPY 46323_at Hs.8859 Ca2+-dependent ER nucleoside diphosphatase -3.0 SHARP 201997_s_at Hs.184245 SMART/HDAC1 associated repressor protein -2.3 SMAP1 218137_s_at Hs.373517 stromal membrane-associated protein -6.5 SMARCA2 206542_s_at Hs.198296 actin dependent regulator of chromatin -2.1 SMARCF1 210649_s_at Hs.123090 actin dependent regulator of chromatin -34.3 SMARCF1 218917_s_at Hs.123090 actin dependent regulator of chromatin -3.6 SMARCF1 212152_x_at Hs.123090 actin dependent regulator of chromatin -3.3 SNRP70 201221_s_at Hs.174051 small nuclear ribonucleoprotein 70kDa polypeptide -2.2 SPG4 209748_at Hs.26334 spastic paraplegia 4 (autosomal dominant; spastin) -37.3 -1.5 spleen focus forming virus proviral integration SPI1 205312_at Hs.157441 oncogene spi1 -3.6 1.6 2.6 SPOP 204640_s_at Hs.129951 speckle-type POZ protein -2.2 SP3 213168_at Hs.154295 Sp3 transcription factor -3.0 SP110 208392_x_at Hs.38125 SP110 nuclear body protein -17.6 -1.6 SP110 209761_s_at Hs.38125 SP110 nuclear body protein -2.6 SP110 209762_x_at Hs.38125 SP110 nuclear body protein -2.7 SP110 208012_x_at Hs.38125 SP110 nuclear body protein -3.1 SRPK2 203182_s_at Hs.78353 SFRS protein kinase 2 -5.6 -1.8 SRPK2 214931_s_at Hs.78353 SFRS protein kinase 2 -2.8 -1.8 SRPR 200918_s_at Hs.75730 signal recognition particle receptor ('docking protein') -2.4 SRP9 201273_s_at Hs.75975 signal recognition particle 9kDa -5.5 SRP14 200007_at Hs.180394 signal recognition particle 14kDa -2.4 SRRM2 207435_s_at Hs.197114 serine/arginine repetitive matrix 2 -2.3 SRRM2 208610_s_at Hs.197114 serine/arginine repetitive matrix 2 -2.6 STAU 207320_x_at Hs.6113 staufen, RNA binding protein (Drosophila) -2.5 STAU 211505_s_at Hs.6113 staufen, RNA binding protein (Drosophila) -2.6 SUPT4H1 201483_s_at Hs.79058 suppressor of Ty 4 homolog 1 (S. cerevisiae) -7.1 SUPT4H1 201484_at Hs.79058 suppressor of Ty 4 homolog 1 (S. cerevisiae) -2.2 TAF4 213090_s_at Hs.24644 TAF4 RNA polymerase II, TBP-associated factor -2.3 -1.7 TFCP2 209338_at Hs.154970 transcription factor CP2 -4.6 TIF1 213301_x_at Hs.183858 transcriptional intermediary factor 1 -4.4 TNRC5 217931_at Hs.56828 trinucleotide repeat containing 5 -55.6 -1.7 TOP2B 211987_at Hs.75248 topoisomerase (DNA) II beta 180kDa -3.2 TRAP240 201987_at Hs.351572 thyroid hormone receptor-associated protein -2.8 TRA2A 213575_at Hs.445652 transformer-2 alpha -2.3 TRA2A 213593_s_at Hs.445652 transformer-2 alpha -5.5

42 TRIM22 213293_s_at Hs.318501 tripartite motif-containing 22 -2.5 TRIM28 200990_at Hs.228059 tripartite motif-containing 28 -4.4 TRIM38 203568_s_at Hs.59545 tripartite motif-containing 38 -2.9 TRIM38 203567_s_at Hs.59545 tripartite motif-containing 38 -14.4 UBTF 202692_s_at Hs.89781 upstream binding transcription factor, RNA pol. I -2.1 UPF2 203519_s_at Hs.3862 UPF2 regulator of nonsense transcripts homolog (yeast) -4.5 U2AF65 218381_s_at Hs.7655 U2 small nuclear ribonucleoprotein auxiliary factor -3.3 XRCC5 208642_s_at Hs.84981 double-strand-break rejoining enzyme -2.3 YY1 201901_s_at Hs.97496 YY1 transcription factor -4.4 YY1 200047_s_at Hs.97496 YY1 transcription factor -3.7 ZDHHC7 218606_at Hs.9725 zinc finger, DHHC domain containing 7 -2.0 ZFP36L2 201368_at Hs.78909 zinc finger protein 36, C3H type-like 2 -11.2 ZFP36L1 211965_at Hs.85155 zinc finger protein 36, C3H type-like 1 -2.5 ZFP36L2 201367_s_at Hs.78909 zinc finger protein 36, C3H type-like 2 -36.8 ZFP36L2 201369_s_at Hs.78909 zinc finger protein 36, C3H type-like 2 -19.1 -1.7 ZFP106 217781_s_at Hs.15220 zinc finger protein 106 -2.8 -1.5 ZNF9 206158_s_at Hs.2110 zinc finger protein 9 -3.4 ZNF148 203318_s_at Hs.355866 zinc finger protein 148 (pHZ-52) -2.3 ZNF161 202173_s_at Hs.223754 zinc finger protein 161 -2.1 ZNF161 202172_at Hs.6557 zinc finger protein 161 -2.7 ZNF200 207338_s_at Hs.88219 zinc finger protein 200 -3.2 ZNF217 203739_at Hs.155040 zinc finger protein 217 -5.0 ZNF238 212774_at Hs.69997 zinc finger protein 238 -8.5 ZNF289 211975_at Hs.256310 zinc finger protein 289, ID1 regulated -3.0 ZNF294 215596_s_at Hs.288773 zinc finger protein 294 -2.4 ZNF313 211678_s_at Hs.10590 zinc finger protein 313 -4.7 -1.5 ZNF313 200867_at Hs.10590 zinc finger protein 313 -13.4 ZNF313 200868_s_at Hs.10590 zinc finger protein 313 -2.4 ZNF350 219266_at Hs.130965 zinc finger protein 350 -3.5

Unknown function Up-regulated (216) ACRV1 207969_x_at Hs.169222 acrosomal vesicle protein 1 2.3 ANKRD12 216563_at Hs.27973 ankyrin repeat domain 12 2.3 ASK 204244_s_at Hs.152759 activator of S phase kinase 3.5 1.8 BAMBI 203304_at Hs.78776 BMP and activin membrane-bound inhibitor homolog 2.5 BEX1 218332_at Hs.334370 brain expressed, X-linked 1 2.3 CDV-1 219372_at Hs.333120 carnitine deficiency-assoc. gene expressed in ventricle 1 2.2 CLDN8 214598_at Hs.162209 claudin 8 3.2 CXorf6 205088_at Hs.20136 chromosome X open reading frame 6 2.7 C5orf13 201310_s_at Hs.413760 chromosome 5 open reading frame 13 2.2 C6.1A 216521_s_at Hs.301927 c6.1A 2.2 C9orf10 210516_at Hs.76666 chromosome 9 open reading frame 10 2.8 C9orf10 200767_s_at Hs.76666 chromosome 9 open reading frame 10 -1.3 1.5 -1.6 -1.7 -1.6 C9orf10 200774_at Hs.76666 chromosome 9 open reading frame 10 -7.5 -1.8 C11ORF4 43934_at Hs.25274 chromosome 11 hypothetical protein ORF4 2.2 C14orf107 220701_at Hs.283057 chromosome 14 open reading frame 107 2.6 C14orf109 213246_at Hs.275352 chromosome 14 open reading frame 109 3.0 1.6 C14orf143 214264_s_at Hs.87819 chromosome 14 open reading frame 143 2.3

43 C17orf1A 215999_at Hs.158313 chromosome 17 open reading frame 1A 2.5 C20orf6 218859_s_at Hs.88820 chromosome 20 open reading frame 6 2.4 C20orf97 218145_at Hs.26802 chromosome 20 open reading frame 97 2.8 C20orf121 219633_at Hs.283869 chromosome 20 open reading frame 121 2.2 1.8 C21orf97 218019_s_at Hs.4746 chromosome 21 open reading frame 97 2.8 DLG3 212729_at Hs.11101 discs, large (Drosophila) homolog 3 2.1 DLG7 203764_at Hs.77695 discs, large homolog 7 (Drosophila) 3.4 DMWD 33768_at Hs.275924 dystrophia myotonica-containing WD repeat motif 2.1 DKFZP586A0522 211424_x_at Hs.288771 DKFZP586A0522 protein 2.3 DKFZP586A0522 209703_x_at Hs.288771 DKFZP586A0522 protein 2.6 DKFZP586L151 213125_at Hs.43658 DKFZP586L151 protein 2.2 -2.3 DKFZp667G2110 213188_s_at Hs.406105 hypothetical protein DKFZp667G2110 2.2 DKFZp761P1010 221696_s_at Hs.24979 hypothetical protein DKFZp761P1010 2.5 1.9 DXS542 222247_at Hs.367752 putative X-linked retinopathy protein 3.3 DXS9928E 203262_s_at Hs.54277 DNA segment on chromosome X 2.2 D6S1101 215810_x_at Hs.278678 Dystonia musculorum of mouse, human homolog of 2.4 ESM1 208394_x_at Hs.41716 endothelial cell-specific molecule 1 2.9 FAM13A1 202972_s_at Hs.177664 family with sequence similarity 13, member A1 2.1 FER1L4 222245_s_at Hs.72222 fer-1-like 4 (C. elegans) 2.5 FLJ10134 219410_at Hs.104800 hypothetical protein FLJ10134 2.9 FLJ10159 218974_at Hs.22505 hypothetical protein FLJ10159 2.5 FLJ10381 220517_at Hs.158370 hypothetical protein FLJ10381 2.0 FLJ10702 217852_s_at Hs.104222 hypothetical protein FLJ10702 2.1 FLJ10726 218314_s_at Hs.268561 hypothetical protein FLJ10726 2.1 -1.7 FLJ10803 213700_s_at Hs.8173 hypothetical protein FLJ10803 4.0 FLJ10849 214293_at Hs.8768 hypothetical protein FLJ10849 3.1 FLJ10858 219502_at Hs.134403 hypothetical protein FLJ10858 2.4 -2.1 FLJ11036 219503_s_at Hs.16740 hypothetical protein FLJ11036 2.7 -1.8 -2.0 FLJ11142 221103_s_at Hs.272244 hypothetical protein FLJ11142 2.8 -1.7 -1.8 FLJ11149 203225_s_at Hs.37558 hypothetical protein FLJ11149 4.9 FLJ11259 218627_at Hs.184465 hypothetical protein FLJ11259 3.0 1.8 FLJ11275 221104_s_at Hs.380421 hypothetical protein FLJ11275 2.4 FLJ12975 206438_x_at Hs.167165 hypothetical protein FLJ12975 4.0 FLJ12985 206557_at Hs.270435 hypothetical protein FLJ12985 2.5 FLJ13195 218994_s_at Hs.213392 hypothetical protein FLJ13195 2.5 1.7 FLJ14106 220348_at Hs.287872 hypothetical protein FLJ14106 2.8 FLJ20069 221569_at Hs.273294 hypothetical protein FLJ20069 2.2 FLJ20152 218532_s_at Hs.82273 hypothetical protein FLJ20152 2.5 FLJ20287 218104_at Hs.26369 hypothetical protein FLJ20287 2.8 1.6 FLJ20581 89977_at Hs.122939 hypothetical protein FLJ20581 2.2 FLJ20604 219133_at Hs.55781 hypothetical protein FLJ20604 2.2 FLJ21168 204665_at Hs.288106 hypothetical protein FLJ21168 2.1 FLJ21415 218867_s_at Hs.120170 hypothetical protein FLJ21415 2.4 FLJ21870 219496_at Hs.130815 hypothetical protein FLJ21870 2.3 FLJ22404 221177_at Hs.287694 hypothetical protein FLJ22404 2.6 FLJ22649 218817_at Hs.42194 hypothetical protein FLJ22649 2.1 -2.3 FLJ22843 220523_at Hs.301143 hypothetical protein FLJ22843 2.8 -1.7 -1.6 -2.1 FLJ23142 219234_x_at Hs.20999 hypothetical protein FLJ23142 2.7 -2.1 FLJ23189 220173_at Hs.287733 hypothetical protein FLJ23189 2.2

44 FLJ23558 220725_x_at Hs.288552 hypothetical protein FLJ23558 2.3 FLJ23560 219487_at Hs.96322 hypothetical protein FLJ23560 2.3 GAGE4 206640_x_at Hs.251677 G antigen 4 2.3 -1.5 GAGE4 207086_x_at Hs.183199 G antigen 4 2.9 GAGE4 208155_x_at Hs.272484 G antigen 4 2.2 GAL 207466_at Hs.278959 galanin 2.3 GPM6A 209469_at Hs.75819 glycoprotein M6A 3.4 G2 214772_at Hs.432369 G2 protein 2.5 1.8 HCGVIII-1 215985_at Hs.153618 HCGVIII-1 protein 2.2 -2.2 HSHIN1 220669_at Hs.252722 Hin-1 2.0 HSU15552 202776_at Hs.85769 acidic 82 kDa protein mRNA 2.4 KIAA0063 201751_at Hs.3094 KIAA0063 gene product 3.5 KIAA0101 202503_s_at Hs.81892 KIAA0101 gene product 2.1 KIAA0298 213748_at Hs.21560 KIAA0298 gene product 2.3 KIAA0322 210331_at Hs.153685 KIAA0322 protein 2.3 KIAA0391 202713_s_at Hs.154668 KIAA0391 gene product 2.1 KIAA0455 213496_at Hs.13245 KIAA0455 gene product 2.4 KIAA0795 207976_at Hs.22926 KIAA0795 protein 2.3 KIAA0802 213358_at Hs.434101 KIAA0802 protein 2.3 -2.3 KIAA0820 209839_at Hs.33578 KIAA0820 protein 2.1 KIAA0830 212573_at Hs.167115 KIAA0830 protein 2.1 KIAA0847 213922_at Hs.125836 tau-tubulin kinase 2.0 -2.0 -1.8 -2.8 KIAA0857 210879_s_at Hs.24557 KIAA0857 protein 2.1 KIAA0934 212503_s_at Hs.227716 KIAA0934 protein 2.2 KIAA1009 206006_s_at Hs.202276 KIAA1009 protein 2.2 KIAA1041 217310_s_at Hs.26023 KIAA1041 protein 2.1 KIAA1233 213974_at Hs.18705 KIAA1233 protein 2.5 KIAA1473 215532_x_at Hs.232108 KIAA1473 protein 2.0 -1.8 -2.8 LATS1 219813_at Hs.324925 LATS, large tumor suppressor, homolog 1 (Drosophila) 3.2 LAT1-3TM 214984_at Hs.325520 LAT1-3TM protein 3.2 LOC114977 206900_x_at Hs.379241 hypothetical protein BC014148 2.1 LOC161291 213285_at Hs.85335 hypothetical protein LOC161291 2.3 LOC221061 212771_at Hs.66762 hypothetical protein LOC221061 2.2 LOC221810 221910_at Hs.150011 hypothetical protein LOC221810 2.0 LOC221823 215486_at Hs.169284 hypothetical protein LOC221823 2.6 LOC221981 214920_at Hs.288681 hypothetical protein LOC221981 4.1 LOC286440 209733_at Hs.348844 hypothetical protein LOC286440 2.7 LOC56906 219596_at Hs.26815 hypothetical protein from EUROIMAGE 511235 2.5 MAG 217102_at Hs.99987 malignancy-associated protein 2.2 MAGEB2 206218_at Hs.113824 melanoma antigen, family B, 2 2.7 MGC13033 209688_s_at Hs.423808 hypothetical protein MGC13033 2.4 MGC14376 214696_at Hs.417157 hypothetical protein MGC14376 4.1 MGC27165 216318_at Hs.366 hypothetical protein MGC27165 2.0 MGC4771 210723_x_at Hs.326743 hypothetical protein MGC4771 2.2 MPDZ 205079_s_at Hs.169378 multiple PDZ domain protein 2.1 MSTP9 215563_s_at Hs.278657 macrophage stimulating, pseudogene 9 2.5 MTMR8 220537_at Hs.196568 myotubularin related protein 8 2.5 MTSS1 210360_s_at Hs.77694 metastasis suppressor 1 2.1 NICE-4 210500_at Hs.8127 NICE-4 protein 2.3

45 PCM1 209997_x_at Hs.75737 pericentriolar material 1 2.2 PEPP2 220952_s_at Hs.86149 phosphoinositol 3-phosphate-binding protein-2 2.2 PER1 36829_at Hs.68398 period homolog 1 (Drosophila) 2.0 PHTF2 217097_s_at Hs.128653 putative homeodomain transcription factor 2 2.5 PLEKHB2 201410_at Hs.351597 pleckstrin homology domain containing, family B 5.3 1.8 PLEKHB2 201411_s_at Hs.246885 pleckstrin homology domain containing, family B 4.5 1.7 PMS2L5 213893_x_at Hs.397073 postmeiotic segregation increased 2-like 5 2.0 PRIM2A 215708_s_at Hs.74519 primase, polypeptide 2A, 58kDa 3.7 PRO0097 220691_at Hs.278928 PRO0097 protein 2.6 -2.4 PRO0159 220853_at Hs.278931 PRO0159 protein 2.2 PRO0386 220873_at Hs.283049 hypothetical protein PRO0386 2.2 PRO1942 221038_at Hs.406703 hypothetical protein PRO1942 2.9 PRO2012 220883_at Hs.283066 hypothetical protein PRO2012 2.8 PSG3 203399_x_at Hs.390278 pregnancy specific beta-1-glycoprotein 3 2.5 PSG6 208106_x_at Hs.252097 pregnancy specific beta-1-glycoprotein 6 2.4 RTP801 202887_s_at Hs.111244 HIF-1 responsive RTP801 3.5 SAM domain, SH3 domain and nuclear localization SAMSN1 220330_s_at Hs.24633 signals, 1 2.3 SCHIP1 204030_s_at Hs.61490 schwannomin interacting protein 1 3.1 SPRR1B 205064_at Hs.1076 small proline-rich protein 1B (cornifin) 2.6 SSX2IP 203015_s_at Hs.22587 synovial sarcoma, X breakpoint 2 interacting protein 2.1 STMN4 221236_s_at Hs.3815 stathmin-like 4 2.4 TBX6 207684_at Hs.198301 T-box 6 2.3 -1.6 TPRA40 218855_at Hs.6418 seven transmembrane domain orphan receptor 5.3 1.6 TPT1 214327_x_at Hs.401448 tumor protein, translationally-controlled 1 1.8 -2.1 -3.6 -1.8 TP53TG3 220167_s_at Hs.278513 TP53TG3 protein 2.1 ULK2 204063_s_at Hs.151406 unc-51-like kinase 2 (C. elegans) 2.1 WDR3 218882_s_at Hs.33085 WD repeat domain 3 2.4 WSB1 201294_s_at Hs.187991 SOCS box-containing WD protein SWiP-1 2.0 --- 216444_at Hs.406835 FLJ14076 fis, clone HEMBB1001925 2.4 --- 216121_at Hs.306323 DKFZp566O053 2.3 1.6 --- 216730_at Hs.306689 FLJ20908 fis, clone ADSE00417 2.3 --- 215854_at Hs.287459 FLJ11844 fis, clone HEMBA1006665 2.3 --- 217629_at Hs.446662 ESTs 2.3 --- 216791_at Hs.306850 FLJ22796 fis, clone KAIA2544 2.2 --- 216723_at Hs.306520 DKFZp434D179 2.2 1.7 --- 215577_at Hs.287474 FLJ12000 fis, clone HEMBB1001531 2.2 --- 216126_at Hs.255021 FLJ12356 fis, clone MAMMA1002339 2.0 --- 216012_at Hs.159901 Human unidentified mRNA, partial sequence 2.3 --- 222180_at Hs.225729 FLJ14122 fis, clone MAMMA1002033 2.0 --- 214218_s_at Hs.351546 FLJ30298 fis, clone BRACE2003172 2.1 --- 213960_at Hs.13223 cDNA clone EUROIMAGE 51358 2.0 --- 215479_at Hs.157392 FLJ20780 fis, clone COL04256 2.1 --- 211931_s_at Hs.356635 ESTs, Highly similar to D10S102 2.1 --- 216753_at Hs.306773 FLJ21499 fis, clone COL05634 2.1 --- 213657_s_at Hs.323053 clone EUROIMAGE 26539 2.1 --- 215376_at Hs.296713 FLJ12295 fis, clone MAMMA1001818 2.0 --- 222376_at Hs.15833 ESTs, Weakly similar to neuronal thread protein 2.2 --- 212607_at Hs.351021 FLJ30547 fis, clone BRAWH2001439 2.2 --- 217482_at Hs.191158 FLJ11925 fis, clone HEMBB1000354 2.2

46 --- 217606_at Hs.196555 DKFZp686P24158 5.7 --- 215643_at Hs.306613 FLJ11740 fis, clone HEMBA1005500 4.6 --- 217695_x_at Hs.343402 ESTs, Weakly similar to hypothetical protein FLJ20489 4.5 --- 214862_x_at Hs.139006 DKFZp564G1162 3.7 --- 215057_at Hs.92683 Homo sapiens clone 161455 3.3 --- 222329_x_at Hs.433051 ESTs, Weakly similar to hypothetical protein FLJ20489 3.2 --- 213929_at Hs.28540 DKFZp586F1223 3.1 1.7 --- 217132_at Hs.137173 Homo sapiens clone 24587 mRNA sequence 3.5 --- 214798_at Hs.205842 DKFZp434L231 3.0 --- 215811_at Hs.275706 Homo sapiens clone GLSH-3 2.9 --- 216529_at Hs.302046 DKFZp564C163 2.9 --- 214053_at Hs.7888 Homo sapiens clone 23736 mRNA sequence 2.9 --- 222328_x_at Hs.283435 FLJ25512 fis, clone CBR06118 2.9 --- 215226_at Hs.321583 FLJ20779 fis, clone COL05077 2.5 --- 222213_x_at Hs.296710 EST, similar to hypothetical protein FLJ20294 2.7 --- 215462_at Hs.421430 FLJ13795 fis, clone THYRO1000107 2.7 --- 216739_at Hs.306684 FLJ20874 fis, clone ADKA02818 2.6 --- 221992_at Hs.347508 FLJ23482 fis, clone KAIA03142 2.6 --- 217548_at Hs.6734 FLJ30690 fis, clone FCBBF2000576 2.6 --- 213832_at Hs.23729 Homo sapiens clone 24405 mRNA sequence 2.4 --- 216722_at Hs.306576 Homo sapiens tumor antigen NA88-A pseudogene 2.4 --- 215143_at Hs.351178 DKFZp586E1120 2.8 -2.6 --- 215284_at Hs.12432 Homo sapiens clone 24407 mRNA sequence 2.4 -1.7 -5.5 --- 217016_x_at Hs.306885 FLJ23172 fis, clone LNG10005 2.3 -1.9 -2.1 -1.5 --- 217541_x_at Hs.228411 DKFZp434A1611 3.2 -2.2 --- 222207_x_at Hs.380443 FLJ20949 fis, clone ADSE01902 2.1 -2.3 -1.6 --- 91816_f_at Hs.123469 ESTs, Weakly similar to LOC51320 2.1 -2.0 --- 208263_at ------2.0 -1.6 -1.7 --- 216374_at ------2.1 -2.0 --- 216453_at ------2.2 -2.0 --- 220874_at ------2.8 -2.4 -3.0 --- 222249_at ------2.1 -1.9 -1.6 --- 215995_x_at ------4.1 -2.1 --- 221137_at ------2.8 --- 216902_s_at ------3.1 --- 216159_s_at ------3.1 --- 217155_at ------3.5 --- 217480_x_at ------2.4 --- 216287_at ------2.4 --- 215755_at ------2.4 --- 217020_at ------2.4 --- 217322_x_at ------2.3 --- 207369_at ------2.3 --- 220859_at ------2.2 --- 215750_at ------2.2 --- 208360_s_at ------2.2 1.6 --- 216821_at ------2.1 --- 220452_x_at ------2.1 --- 216828_at ------2.0

47 --- 215602_at ------2.0 --- 221339_at ------2.0 -- 211641_x_at Hs.153261 -- 2.6 -- 220436_at Hs.212839 -- 2.7 --- 216712_at ------3.0 --- 216582_at ------2.6 --- 216696_s_at ------2.5 --- 211454_x_at ------2.5 -- 216540_at Hs.74647 -- 2.2

Down-regulated (247) BHC80 203278_s_at Hs.106826 BRAF35/HDAC2 complex (80 kDa) -6.2 BM045 218506_x_at Hs.8750 uncharacterized bone marrow protein BM045 -2.9 4.2 CAP350 204373_s_at Hs.92200 centrosome-associated protein 350 -3.3 CGI-27 219065_s_at Hs.20814 C21orf19-like protein -8.0 CGI-32 218970_s_at Hs.16606 CGI-32 protein -6.5 CGI-43 201973_s_at Hs.289112 CGI-43 protein -4.1 CGI-85 218242_s_at Hs.442630 CGI-85 protein -4.2 CGI-127 217783_s_at Hs.184542 yippee protein -2.6 CG005 202258_s_at Hs.23518 hypothetical protein from BCRA2 region -3.4 CG005 221899_at Hs.23518 hypothetical protein from BCRA2 region -2.5 CL25022 217883_at Hs.5324 hypothetical protein CL25022 -2.5 C1orf8 200620_at Hs.416495 chromosome 1 open reading frame 8 -2.6 C1orf24 217966_s_at Hs.48778 chromosome 1 open reading frame 24 -2.9 2.3 C1orf24 217967_s_at Hs.48778 chromosome 1 open reading frame 24 -3.0 2.2 C1orf37 212165_at Hs.17481 chromosome 1 open reading frame 37 -3.1 C1orf38 207571_x_at Hs.10649 chromosome 1 open reading frame 38 -3.3 C1orf38 210785_s_at Hs.10649 chromosome 1 open reading frame 38 -3.7 C2orf6 201297_s_at Hs.196437 chromosome 2 open reading frame 6 -2.0 C2orf6 214812_s_at Hs.196437 chromosome 2 open reading frame 6 -3.4 C4orf8 203600_s_at Hs.325987 chromosome 4 open reading frame 8 -2.1 C5orf5 218518_at Hs.82035 chromosome 5 open reading frame 5 -2.2 C5orf6 218023_s_at Hs.102469 chromosome 5 open reading frame 6 -2.0 C5orf7 201643_x_at Hs.24125 chromosome 5 open reading frame 7 -2.4 C5orf7 210878_s_at Hs.24125 chromosome 5 open reading frame 7 -3.2 C6orf9 204265_s_at Hs.288316 chromosome 6 open reading frame 9 -2.5 C6orf32 209829_at Hs.101359 chromosome 6 open reading frame 32 -2.7 C6orf37 221766_s_at Hs.10784 chromosome 6 open reading frame 37 -9.5 C6orf62 213872_at Hs.7779 chromosome 6 open reading frame 62 -2.9 1.7 C6orf80 209479_at Hs.44468 chromosome 6 open reading frame 80 -4.3 C7orf19 218812_s_at Hs.289053 chromosome 7 open reading frame 19 -4.3 C10orf7 201725_at Hs.82043 chromosome 10 open reading frame 7 -2.1 C11orf10 218213_s_at Hs.90918 chromosome 11 open reading frame 10 -7.6 2.2 C13orf18 44790_s_at Hs.288708 chromosome 13 open reading frame 18 -5.2 C13orf18 219471_at Hs.288708 chromosome 13 open reading frame 18 -3.6 C14orf11 202623_at Hs.433269 chromosome 14 open reading frame 11 -9.9 C14orf108 218139_s_at Hs.106210 chromosome 14 open reading frame 108 -6.0 C14orf116 218031_s_at Hs.60548 chromosome 14 open reading frame 116 -11.9 C14orf117 220494_s_at Hs.103189 chromosome 14 open reading frame 117 -5.0

48 C14orf138 212870_at Hs.406365 chromosome 14 open reading frame 138 -4.7 C14orf138 218940_at Hs.13056 chromosome 14 open reading frame 138 -7.2 C19orf7 213390_at Hs.72134 chromosome 19 open reading frame 7 -6.4 2.5 C20orf24 217835_x_at Hs.184062 chromosome 20 open reading frame 24 -2.3 C20orf43 217737_x_at Hs.182281 chromosome 20 open reading frame 43 -2.2 C20orf104 209422_at Hs.301055 chromosome 20 open reading frame 104 -8.1 C20orf104 209423_s_at Hs.301055 chromosome 20 open reading frame 104 2.1 1.6 -2.1 C22orf19 209418_s_at Hs.75361 chromosome 22 open reading frame 19 -2.3 C22orf19 209419_at Hs.75361 chromosome 22 open reading frame 19 3.0 -3.7 DJ465N24.2.1 209006_s_at Hs.8084 hypothetical protein dJ465N24.2.1 -3.6 DJ465N24.2.1 209007_s_at Hs.8084 hypothetical protein dJ465N24.2.1 -3.1 DJ971N18.2 201581_at Hs.169358 hypothetical protein DJ971N18.2 -6.3 DKFZP434C171 212886_at Hs.209100 DKFZP434C171 protein -18.0 2.1 DKFZP434D1335 212131_at Hs.8258 DKFZP434D1335 protein -2.8 DKFZP434D1335 212132_at Hs.8258 DKFZP434D1335 protein -2.5 DKFZP434B044 221541_at Hs.262958 hypothetical protein DKFZp434B044 -8.3 DKFZP434J154 202031_s_at Hs.226372 DKFZP434J154 protein -11.4 DKFZP434J154 204710_s_at Hs.226372 DKFZP434J154 protein -2.4 DKFZp564B0769 212179_at Hs.18368 SR rich protein -2.9 DKFZp564B0769 212176_at Hs.18368 SR rich protein -2.2 DKFZP564J157 204031_s_at Hs.63525 DKFZp564J157 protein -4.2 DKFZP564O0523 221596_s_at Hs.21590 hypothetical protein DKFZp564O0523 -7.9 DKFZP566A1524 208092_s_at Hs.4863 hypothetical protein DKFZp566A1524 -2.1 1.5 DKFZP566A1524 209683_at Hs.4863 hypothetical protein DKFZp566A1524 -12.0 2.1 DKFZP566H073 212047_s_at Hs.7158 DKFZP566H073 protein -3.4 DKFZP586O0120 201863_at Hs.4766 DKFZP586O0120 protein -2.2 DKFZp667O2416 212860_at Hs.19066 hypothetical protein DKFZp667O2416 -5.0 DKFZp762C186 91703_at Hs.356684 hypothetical protein DKFZp762C186 -3.6 DKFZp762C186 221755_at Hs.356684 hypothetical protein DKFZp762C186 -14.0 DXYS155E 203624_at Hs.21595 DNA segment on chromosome X and Y -2.5 D1S155E 219939_s_at Hs.69855 NRAS-related gene -2.2 EDRF1 213410_at Hs.227209 erythroid differentiation-related factor 1 -2.2 FAM8A1 203420_at Hs.95260 family with sequence similarity 8, member A1 -2.7 FLJ10154 218067_s_at Hs.179972 hypothetical protein FLJ10154 -2.9 FLJ10276 222200_s_at Hs.333149 hypothetical protein FLJ10276 -4.8 FLJ10290 218134_s_at Hs.25516 hypothetical protein FLJ10290 -2.9 FLJ10350 217943_s_at Hs.177596 hypothetical protein FLJ10350 -3.0 FLJ10404 218920_at Hs.111279 hypothetical protein FLJ10404 -2.2 FLJ10652 218614_at Hs.236844 hypothetical protein FLJ10652 -2.1 FLJ10707 221806_s_at Hs.7187 hypothetical protein FLJ10707 -2.2 2.3 FLJ10856 217743_s_at Hs.108530 hypothetical protein FLJ10856 -2.5 FLJ10898 218659_at Hs.13801 KIAA1685 protein -2.7 FLJ11151 218610_s_at Hs.14992 hypothetical protein FLJ11151 -10.0 FLJ11240 218191_s_at Hs.339833 hypothetical protein FLJ11240 -3.5 FLJ11838 218341_at Hs.72531 hypothetical protein FLJ11838 -2.9 FLJ12150 218154_at Hs.118983 hypothetical protein FLJ12150 -3.6 -1.9 FLJ12168 218466_at Hs.325860 hypothetical protein FLJ12168 -8.0 FLJ12671 212766_s_at Hs.301904 hypothetical protein FLJ12671 -3.9 FLJ13052 208919_s_at Hs.220324 NAD kinase -2.4

49 FLJ13055 218509_at Hs.6846 hypothetical protein FLJ13055 -6.7 FLJ13213 217828_at Hs.331328 hypothetical protein FLJ13213 -6.8 FLJ13409 220933_s_at Hs.30732 hypothetical protein FLJ13409 -5.1 FLJ13910 212482_at Hs.75277 hypothetical protein FLJ13910 -2.6 FLJ14753 211185_s_at Hs.13453 hypothetical protein FLJ14753 -2.4 FLJ20040 218474_s_at Hs.61960 hypothetical protein FLJ20040 -4.1 FLJ20054 219696_at Hs.101590 hypothetical protein FLJ20054 -5.4 FLJ20073 219691_at Hs.65641 hypothetical protein FLJ20073 -4.8 FLJ20136 218396_at Hs.24817 hypothetical protein FLJ20136 -2.0 FLJ20189 219069_at Hs.29052 hypothetical protein FLJ20189 -7.0 2.5 FLJ20288 208772_at Hs.84045 FLJ20288 protein -4.2 FLJ20274 206555_s_at Hs.268371 hypothetical protein FLJ20274 -17.7 2.0 FLJ20297 207856_s_at Hs.94491 hypothetical protein FLJ20297 -3.3 FLJ20507 219460_s_at Hs.202955 hypothetical protein FLJ20507 -3.9 FLJ20730 218519_at Hs.237480 hypothetical protein FLJ20730 -3.4 FLJ20752 217987_at Hs.101364 hypothetical protein FLJ20752 -2.4 FLJ21016 218107_at Hs.289069 hypothetical protein FLJ21016 -2.5 FLJ21439 203513_at Hs.288872 hypothetical protein FLJ21439 -3.1 FLJ22059 221844_x_at Hs.13323 hypothetical protein FLJ22059 -2.6 FLJ22332 219221_at Hs.111092 hypothetical protein FLJ22332 -2.5 FLJ22635 219359_at Hs.353181 hypothetical protein FLJ22635 -2.0 FLJ22662 218454_at Hs.178470 hypothetical protein FLJ22662 -2.7 FLJ22679 220486_x_at Hs.5472 hypothetical protein FLJ22679 -3.0 FLJ22794 218248_at Hs.19525 hypothetical protein FLJ22794 -2.6 FLJ23091 221958_s_at Hs.250746 hypothetical protein FLJ23091 -15.3 FLJ23360 221064_s_at Hs.161279 hypothetical protein FLJ23360 -4.8 FLJ34588 212410_at Hs.375580 hypothetical protein FLJ34588 -6.5 FLJ90005 213038_at Hs.352358 hypothetical protein FLJ90005 -3.5 FLJ90005 36564_at Hs.352358 hypothetical protein FLJ90005 -2.6 2.1 HEBP2 203430_at Hs.111029 heme binding protein 2 -3.2 -1.5 HEM1 217549_at Hs.446638 hematopoietic protein 1 -10.1 HIS1 202814_s_at Hs.15299 HMBA-inducible -3.6 HSPC016 221791_s_at Hs.397853 hypothetical protein HSPC016 -3.1 HSPC177 219356_s_at Hs.36237 hypothetical protein HSPC177 -5.2 HT011 221804_s_at Hs.267923 uncharacterized hypothalamus protein HT011 -4.0 HYPB 212493_s_at Hs.6947 huntingtin interacting protein B -4.4 H41 212010_s_at Hs.283690 hypothetical protein H41 -2.7 IDN3 212469_at Hs.225767 IDN3 protein -4.5 IDN3 212483_at Hs.225767 IDN3 protein -2.2 IDN3 213918_s_at Hs.225767 IDN3 protein -3.1 JM5 209216_at Hs.21753 JM5 protein -7.2 JM5 209217_s_at Hs.21753 JM5 protein -2.2 KIAA0053 38149_at Hs.1528 KIAA0053 gene product -3.8 KIAA0053 204882_at Hs.1528 KIAA0053 gene product -8.0 2.5 KIAA0073 213483_at Hs.1191 KIAA0073 protein -2.0 KIAA0092 203494_s_at Hs.151791 KIAA0092 gene product -3.6 KIAA0138 32099_at Hs.159384 KIAA0138 gene product -3.8 KIAA0174 200851_s_at Hs.75824 KIAA0174 gene product -3.6 KIAA0205 202651_at Hs.3610 KIAA0205 gene product -7.6

50 KIAA0217 208953_at Hs.78851 KIAA0217 protein -2.5 KIAA0222 203604_at Hs.48450 KIAA0222 gene product -2.8 -1.7 KIAA0232 212441_at Hs.79276 KIAA0232 gene product -3.1 KIAA0240 38892_at Hs.196275 KIAA0240 protein -25.3 KIAA0240 213208_at Hs.196275 KIAA0240 protein -17.0 KIAA0252 212301_at Hs.83419 KIAA0252 protein -2.4 KIAA0256 212450_at Hs.432934 KIAA0256 gene product -6.0 KIAA0317 202128_at Hs.20126 KIAA0317 gene product -2.6 KIAA0342 213261_at Hs.16950 KIAA0342 gene product -8.1 KIAA0349 212756_s_at Hs.15303 ubiquitin ligase E3 alpha-II -7.8 KIAA0399 212601_at Hs.100955 KIAA0399 protein -11.1 KIAA0433 203253_s_at Hs.26179 KIAA0433 protein -2.1 1.5 KIAA0446 32091_at Hs.158286 KIAA0446 gene product -5.5 KIAA0447 217122_s_at Hs.214646 KIAA0447 gene product -4.9 KIAA0513 204546_at Hs.301658 KIAA0513 gene product -5.1 KIAA0528 212943_at Hs.30656 KIAA0528 gene product -3.8 KIAA0540 212443_at Hs.64742 KIAA0540 protein -3.7 KIAA0561 213045_at Hs.173864 KIAA0561 protein -2.4 1.6 KIAA0599 212823_s_at Hs.198037 KIAA0599 protein -4.9 KIAA0625 201965_s_at Hs.154919 KIAA0625 protein -7.1 -1.8 KIAA0625 201964_at Hs.154919 KIAA0625 protein -6.9 KIAA0685 202791_s_at Hs.296406 KIAA0685 gene product -2.7 KIAA0701 213118_at Hs.153293 KIAA0701 protein -9.1 KIAA0804 209553_at Hs.7316 KIAA0804 protein -2.5 KIAA0826 212546_s_at Hs.169600 KIAA0826 protein -2.6 KIAA0870 212975_at Hs.18166 KIAA0870 protein -3.3 KIAA0870 212974_at Hs.18166 KIAA0870 protein -2.1 KIAA0876 212495_at Hs.301011 KIAA0876 protein -9.7 -1.7 KIAA0924 205594_at Hs.190386 KIAA0924 protein -45.2 KIAA0937 212611_at Hs.62264 KIAA0937 protein -2.2 KIAA1012 207305_s_at Hs.42959 KIAA1012 protein -2.3 KIAA1025 212209_at Hs.4084 KIAA1025 protein -4.3 KIAA1025 212207_at Hs.4084 KIAA1025 protein -2.0 KIAA1028 212899_at Hs.129836 KIAA1028 protein -4.2 KIAA1033 212795_at Hs.12144 KIAA1033 protein -3.4 KIAA1039 213280_at Hs.301552 KIAA1039 protein -10.3 -1.5 KIAA1040 212754_s_at Hs.9846 KIAA1040 protein -2.1 KIAA1041 206015_s_at Hs.26023 KIAA1041 protein -2.7 KIAA1049 213311_s_at Hs.227835 KIAA1049 protein -7.7 -1.5 KIAA1076 213153_at Hs.154525 KIAA1076 protein -3.4 KIAA1185 212904_at Hs.268488 KIAA1185 protein -15.6 2.2 KIAA1280 219520_s_at Hs.12913 KIAA1280 protein -3.9 KIAA1536 209002_s_at Hs.156667 KIAA1536 protein -2.4 KIAA1718 221778_at Hs.222707 KIAA1718 protein -4.1 KLHDC2 217906_at Hs.20597 kelch domain containing 2 -2.3 LAPTM5 201720_s_at Hs.79356 Lysosomal-assoc. multispanning membrane protein-5 -3.2 LDB1 35160_at Hs.26002 LIM domain binding 1 -2.1 LOC115207 212192_at Hs.109438 hypothetical protein BC013764 -43.0 -1.6 LOC137886 212934_at Hs.155572 hypothetical protein LOC137886 -3.5

51 LOC148936 215555_at Hs.273099 hypothetical protein LOC148936 -17.2 LOC220594 213510_x_at Hs.234573 TL132 protein -2.1 LOC283820 217225_x_at Hs.227823 hypothetical protein LOC283820 -5.0 LOC340318 213360_s_at Hs.295112 hypothetical protein -2.1 LOC51142 217720_at Hs.180859 16.7Kd protein -2.4 LOC51231 221998_s_at Hs.98289 VRK3 for vaccinia related kinase 3 -2.4 LOC58486 218263_s_at Hs.25726 transposon-derived Buster1 transposase-like protein -8.2 LOC90379 91952_at Hs.298553 hypothetical protein BC002926 -2.8 LOC91300 221764_at Hs.388956 hypothetical protein BC012775 -5.9 MAGOH 210092_at Hs.57904 mago-nashi homolog, proliferation-associated -5.0 MAK3P 217745_s_at Hs.288932 likely ortholog of mouse Mak3p homolog -2.1 MGC11061 209551_at Hs.66309 hypothetical protein MGC11061 -2.6 MGC14697 213408_s_at Hs.171625 hypothetical protein MGC14697 -2.3 MGC2718 47083_at Hs.81057 hypothetical protein MGC2718 -2.9 MGC2963 221255_s_at Hs.30011 hypothetical protein MGC2963 -2.7 MGC3035 218037_at Hs.22412 hypothetical protein MGC3035 -2.1 MGC3035 221983_at Hs.22412 hypothetical protein MGC3035 -2.5 MGC3121 218714_at Hs.293629 hypothetical protein MGC3121 -7.4 2.6 MGC3121 45687_at Hs.293629 hypothetical protein MGC3121 -1.1 1.9 MGC3123 218419_s_at Hs.288600 hypothetical protein MGC3123 -2.1 MGC3222 217795_s_at Hs.323193 hypothetical protein MGC3222 -10.9 MGC4368 218130_at Hs.9732 hypothetical protein MGC4368 -13.5 MGC4342 217992_s_at Hs.301342 hypothetical protein MGC4342 -2.8 MGC5466 212129_at Hs.83724 hypothetical protein MGC5466 -8.8 MGC8721 200847_s_at Hs.279921 hypothetical protein MGC8721 -5.4 MLF2 200948_at Hs.79026 myeloid leukemia factor 2 -3.5 -1.5 MO25 217873_at Hs.6406 MO25 protein -5.6 M11S1 200723_s_at Hs.278672 membrane component, chrom. 11, surface marker 1 -2.4 M17S2 201384_s_at Hs.277721 membrane component, chrom. 17, surface marker 2 -3.0 M17S2 201383_s_at Hs.277721 membrane component, chrom. 17, surface marker 2 -2.4 NDP52 210817_s_at Hs.154230 nuclear domain 10 protein -2.5 NIFU 209075_s_at Hs.9908 nitrogen fixation cluster-like -3.5 NOC4 218057_x_at Hs.173162 neighbor of COX4 -5.4 NPD009 209460_at Hs.283675 NPD009 protein -13.1 NUMB 207545_s_at Hs.78890 numb homolog (Drosophila) -2.4 NUMB 209073_s_at Hs.78890 numb homolog (Drosophila) -2.7 PCNP 217816_s_at Hs.71618 PEST-containing nuclear protein -5.8 PCNX 213159_at Hs.55947 pecanex homolog (Drosophila) -5.1 PCTP 218676_s_at Hs.285218 phosphatidylcholine transfer protein -22.9 2.2 PHC2 200919_at Hs.165263 polyhomeotic-like 2 (Drosophila) -2.5 PREI3 202918_s_at Hs.107942 preimplantation protein 3 -2.8 PRO2198 219999_at Hs.116459 hypothetical protein PRO2198 -3.5 -1.8 PRO2730 201934_at Hs.194110 hypothetical protein PRO2730 -4.6 PUM2 201493_s_at Hs.6151 pumilio homolog 2 (Drosophila) -2.2 RPAC2 218258_at Hs.106127 likely ortholog of mouse RNA polymerase 1-3 -3.2 PTD008 217780_at Hs.108969 PTD008 protein -8.3 2.3 RTN3 219549_s_at Hs.252831 reticulon 3 -4.9 RW1 212507_at Hs.75912 likely ortholog of mouse Rw1 -2.7 SEL1L 202061_s_at Hs.181300 sel-1 suppressor of lin-12-like (C. elegans) -2.6

52 SMAP 201784_s_at Hs.78050 small acidic protein -12.0 SMP1 217766_s_at Hs.107979 small membrane protein 1 -2.7 SP192 217877_s_at Hs.169854 hypothetical protein SP192 -3.3 SSA2 210438_x_at Hs.554 Sjogren syndrome antigen A2 -6.6 SSA2 212852_s_at Hs.554 Sjogren syndrome antigen A2 -2.5 SSB3 46256_at Hs.7247 SPRY domain-containing SOCS box protein SSB-3 -2.4 SSFA2 202506_at Hs.351355 sperm specific antigen 2 -2.0 SWAP70 209307_at Hs.153026 SWAP-70 protein -2.6 S164 212031_at Hs.180789 S164 protein -5.4 TACC1 200911_s_at Hs.173159 transforming, acidic coiled-coil containing protein 1 -4.1 TAGLN2 210978_s_at Hs.406504 transgelin 2 -3.4 TDE2 208671_at Hs.146668 tumor differentially expressed 2 -3.1 TEB4 201737_s_at Hs.380875 similar to S. cerevisiae SSM4 -2.9 TM6SF1 209525_at Hs.341203 transmembrane 6 superfamily member 1 -2.7 TM6SF1 219892_at Hs.341203 transmembrane 6 superfamily member 1 -2.4 UBQLN2 215884_s_at Hs.4552 ubiquilin 2 -2.3 VMP1 220990_s_at Hs.166254 likely ortholog of rat vacuole membrane protein 1 -8.5 WBSCR5 221581_s_at Hs.56607 Williams-Beuren syndrome chromosome region 5 -8.7 WBSCR5 211768_at Hs.56607 Williams-Beuren syndrome chromosome region 5 1.3 -2.1 WBSCR20A 213773_x_at Hs.272820 Williams Beuren syndrome chromosome region 20A -2.2 XTP2 211946_s_at Hs.69559 HBxAg transactivated protein 2 -2.1 13CDNA73 204072_s_at Hs.181304 hypothetical protein CG003 -4.9 --- 214753_at Hs.110630 Human BRCA2 region, mRNA sequence CG006 -6.6 --- 216109_at Hs.306803 FLJ21695 fis, clone COL09653 -9.3 --- 212888_at Hs.325625 FLJ33775 fis, clone BRSSN2000498 -7.1 --- 216782_at Hs.306863 FLJ23026 fis, clone LNG01738 -4.5 --- 212708_at Hs.184779 DKFZp586B1922 -5.0 --- 213165_at Hs.323748 Homo sapiens clone CDABP0086 mRNA sequence -4.8 --- 201648_at Hs.406107 Human HepG2 partial cDNA, clone hmd3f07m5 -3.4 --- 43511_s_at Hs.22483 Homo sapiens mRNA; cDNA DKFZp762M127 -2.3 --- 222111_at Hs.61773 FLJ11648 fis, clone HEMBA1004405 -2.3 --- 214665_s_at Hs.356550 FLJ20088 fis, clone COL03869 -2.9 --- 212829_at Hs.57079 FLJ13267 fis, clone OVARC1000964 -2.9 --- 212608_s_at Hs.188882 Homo sapiens clone 23872 mRNA sequence -2.9 --- 216176_at Hs.306802 FLJ21690 fis, clone COL09538 -2.7 --- 202615_at Hs.356786 DKFZp686D0521 -2.4 --- 212177_at Hs.414993 ESTs, Moderately similar to SR rich protein -2.2 --- 212547_at Hs.6580 Homo sapiens clone 23718 mRNA sequence -2.1 --- 217529_at Hs.440667 ESTs, Moderately similar to FLJ20489 -3.3 --- 39891_at Hs.323053 Homo sapiens cDNA clone EUROIMAGE 26539 -2.5 2.2 --- 220712_at ------2.7 --- 217202_s_at ------2.8 --- 215558_at ------2.6

A. phagocytophilum and/or S. aureus (fold change between 1.5 & 2.0) Up-regulated (68) AK2 205996_s_at Hs.294008 adenylate kinase 2 1.1 1.5 ARIH1 201879_at Hs.181461 ubiquitin-conjugating enzyme E2 binding protein 1.4 1.7 CANX 208853_s_at Hs.155560 calnexin 1.0 1.6 1.6

53 CES1 209616_s_at Hs.76688 carboxylesterase 1 1.1 1.9 1.7 CHST2 203921_at Hs.8786 carbohydrate sulfotransferase 2 1.4 1.5 CMAH 205518_s_at Hs.24697 CMP-N-acetylneuraminate monooxygenase 1.1 1.6 DARS 201624_at Hs.125453 aspartyl-tRNA synthetase 1.5 1.7 FACL3 201661_s_at Hs.268012 fatty-acid-Coenzyme A ligase, long-chain 3 1.2 1.7 -1.7 HMGCL 202772_at Hs.831 3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase 1.0 1.6 HMGCS1 221750_at Hs.77910 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 1.0 1.5 PCOLN3 201933_at Hs.183138 procollagen (type III) N-endopeptidase -1.9 1.5 -1.6 1.6 PEX6 320_at Hs.301636 peroxisomal biogenesis factor 6 1.8 1.6 PIGA 205281_s_at Hs.51 phosphatidylinositol glycan, class A 1.9 1.7 PMAIP1 204285_s_at Hs.96 phorbol-12-myristate-13-acetate-induced protein 1 1.0 1.9 1.7 PSMA6 208805_at Hs.410276 proteasome subunit, alpha type, 6 1.4 1.5 1.6 2.2 PSMD12 202352_s_at Hs.4295 proteasome 26S subunit, non-ATPase, 12 -1.3 1.5 SERPINE2 212190_at Hs.21858 serine (or cysteine) proteinase inhibitor, clade E 2.3 1.9 -2.3 SIAH1 202981_x_at Hs.295923 seven in absentia homolog 1 (Drosophila) -1.2 1.5 SIAT4A 208322_s_at Hs.301698 sialyltransferase 4A 1.1 1.5 1.5 SPG20 212526_at Hs.118087 spastic paraplegia 20, spartin 1.2 1.6 SSR2 200652_at Hs.74564 signal sequence receptor, beta -1.0 1.5 101F6 209665_at Hs.149443 putative tumor suppressor 101F6 -1.3 1.6 BIGM103 209267_s_at Hs.284205 BCG-induced gene in monocytes, clone 103 1.5 1.6 1.6 CAMKK2 212252_at Hs.108708 calcium/calmodulin-dependent prot. kinase kinase 2, β 1.3 1.6 CD59 200985_s_at Hs.278573 CD59 antigen p18-20 1.1 1.6 1.6 DDEF1 221039_s_at Hs.10669 development and differentiation enhancing factor 1 -1.1 1.7 1.6 G3BP2 208841_s_at Hs.433496 Ras-GAP SH3 domain-binding protein 2 -1.1 1.6 GMFB 202543_s_at Hs.151413 glia maturation factor, beta 1.4 1.9 -1.7 IL7R 205798_at Hs.362807 interleukin 7 receptor -1.4 1.5 1.6 PIASY 212881_at Hs.105779 protein inhibitor of activated STAT protein PIASy -1.1 -1.6 1.6 RI58 203595_s_at Hs.27610 retinoic acid- and interferon-inducible protein (58kD) -1.4 1.5 TRA@ 215769_at Hs.74647 T cell receptor alpha locus 1.5 1.7 TRAF6 205558_at Hs.90957 TNF receptor-associated factor 6 1.3 1.5 FBS1 218255_s_at Hs.77735 fibrosin 1 1.4 1.5 1.6 CAPN7 203356_at Hs.377946 calpain 7 -1.3 1.8 ITGAM 205786_s_at Hs.172631 CD11b antigen -1.2 1.5 2.1 ITGB1 211945_s_at Hs.287797 CD29 antigen 1.2 1.6 1.5 LAMP1 201551_s_at Hs.150101 lysosomal-associated membrane protein 1 1.3 3.2 1.6 1.8 LIM 203243_s_at Hs.154103 LIM protein -1.1 1.6 SLK 206875_s_at Hs.105751 Ste20-related serine/threonine kinase 1.1 1.6 1.8 sparc/osteonectin, cwcv & kazal-like domains SPOCK2 202523_s_at Hs.74583 proteoglycan 1.3 1.6 CASP4 209310_s_at Hs.74122 caspase 4, apoptosis-related cysteine protease 1.1 2.2 MT1G 204745_x_at Hs.433391 metallothionein 1G 1.2 1.6 OGFR 211512_s_at Hs.67896 opioid growth factor receptor -1.1 1.5 1.6 UGCG 204881_s_at Hs.432605 UDP-glucose ceramide glucosyltransferase 1.3 1.6 1.5 1.8 1.8 BTG2 201236_s_at Hs.75462 BTG family, member 2 -1.1 2.0 PREB 217861_s_at Hs.279784 prolactin regulatory element binding 1.0 1.7 PRPF4B 202127_at Hs.198891 PRP4 pre-mRNA processing factor 4 homolog B (yeast) -1.2 1.5 PDX1 203067_at Hs.351622 E3-binding protein 1.2 1.6 SFRS6 206108_s_at Hs.6891 splicing factor, arginine/serine-rich 6 -1.1 1.7 TRIP-Br2 202656_s_at Hs.77293 transcriptional regulator -1.2 1.9 1.7 1.6 TRIP-Br2 202657_s_at Hs.77293 transcriptional regulator -1.3 2.2 1.7

54 NPAT 209798_at Hs.89385 nuclear protein, ataxia-telangiectasia locus 1.7 1.8 hnRNPA3: 211933_s_at Hs.249247 heterogeneous nuclear ribonucleoprotein A3 1.6 1.7 hnRNPA3: 211932_at Hs.249247 heterogeneous nuclear ribonucleoprotein A3 1.4 -1.7 ZFX 207920_x_at Hs.2074 zinc finger protein, X-linked 1.4 1.5 C21orf91 220941_s_at Hs.49391 chromosome 21 open reading frame 91 1.2 1.8 FLJ20038 218823_s_at Hs.72071 hypothetical protein FLJ20038 1.4 1.5 OSTM1 218196_at Hs.163724 osteopetrosis associated transmembrane protein 1 1.3 1.9 KIAA0103 203584_at Hs.154387 KIAA0103 gene product 1.4 1.8 KIAA0415 209912_s_at Hs.229950 KIAA0415 gene product 1.0 1.6 1.7 KIAA0592 212929_s_at Hs.439367 KIAA0592 protein -1.1 1.9 -1.6 1.7 MGC8902 201103_x_at Hs.323463 hypothetical protein MGC8902 1.3 1.5 PHF11 221816_s_at Hs.279799 PHD finger protein 11 -1.4 1.5 WAC 217742_s_at Hs.70333 WW domain-cont. adapter with a coiled-coil region -1.1 1.8 FLJ20811 214749_s_at Hs.83530 hypothetical protein FLJ20811 1.6 1.5 --- 214186_s_at Hs.132807 Homo sapiens MHC class I mRNA fragment 1.1 1.8 --- 212847_at Hs.22370 Homo sapiens mRNA; cDNA DKFZp564O0122 1.3 1.9 --- 217637_at Hs.285050 FLJ30824 fis, clone FEBRA2001698 2.3 1.6 -1.8 --- 215604_x_at ------1.0 1.7 -2.2 1.7

Down-regulated (80) ALAS1 205633_s_at Hs.78712 aminolevulinate, delta-, synthase 1 -3.0 -1.5 ANXA7 201366_at Hs.386741 annexin A7 -1.9 -1.7 RPS11 200031_s_at Hs.182740 ribosomal protein S11 -1.7 -1.6 ADSL 202144_s_at Hs.75527 adenylosuccinate lyase 1.1 -1.7 -1.6 AHCY 200903_s_at Hs.172673 S-adenosylhomocysteine hydrolase 1.2 -1.7 SLC30A9 202614_at Hs.270956 solute carrier family 30 (zinc transporter), member 9 1.4 -1.6 -1.5 EEF1A1 204892_x_at Hs.422118 eukaryotic translation elongation factor 1 alpha 1 1.3 -1.7 EGLN2 220956_s_at Hs.324277 egl nine homolog 2 (C. elegans) -1.4 -2.2 -1.6 ETFA 201931_at Hs.169919 electron-transfer-flavoprotein, alpha polypeptide 1.5 -1.6 -1.6 FABP5 202345_s_at Hs.408061 fatty acid binding protein 5 1.0 -1.6 -2.0 -1.7 -2.2 SLC12A9 220371_s_at Hs.119178 solute carrier family 12, member 9 1.1 -1.6 GLRX2 219933_at Hs.5054 glutaredoxin 2 -1.0 -1.6 -1.5 LYPLA2 215566_x_at Hs.283655 lysophospholipase II 1.4 -1.6 MAN1A1 221760_at Hs.25253 mannosidase, alpha, class 1A, member 1 -1.1 -2.0 RAB33B 221014_s_at Hs.183690 RAB33B, member RAS oncogene family -1.4 -1.9 -1.9 -1.8 RPL18A 200869_at Hs.337766 ribosomal protein L18a -1.4 -1.7 RPL3 201217_x_at Hs.119598 ribosomal protein L3 -1.0 -1.5 RPL39 208695_s_at Hs.300141 ribosomal protein L39 -1.4 -1.6 RPL5 213080_x_at Hs.180946 ribosomal protein L5 1.1 -1.5 RPL13 212191_x_at Hs.431392 ribosomal protein L13 -1.3 -1.5 RPS17 212578_x_at Hs.5174 ribosomal protein S17 -1.1 -1.6 RPS18 201049_s_at Hs.275865 ribosomal protein S18 -1.2 -1.8 RPS6KA3 203843_at Hs.173965 ribosomal protein S6 kinase, 90kDa, polypeptide 3 1.1 -1.5 SEC23B 201582_at Hs.173497 Sec23 homolog B (S. cerevisiae) -1.3 -1.8 2.5 TNKS 202561_at Hs.131814 ADP-ribose polymerase 1.3 -1.7 -1.8 UBE2N 201524_x_at Hs.75355 ubiquitin-conjugating enzyme E2N 1.0 -1.6 VAMP2 201557_at Hs.25348 vesicle-associated membrane prot. 2 (synaptobrevin 2) -1.2 -1.6 CDC16 202717_s_at Hs.1592 CDC16 cell division cycle 16 homolog (S. cerevisiae) 1.1 -1.5 GMCL 218458_at Hs.243122 germ cell-less homolog (Drosophila) 1.0 1.9 -1.6 -2.0

55 RAD1 204461_x_at Hs.7179 RAD1 homolog (S. pombe) 1.0 -1.9 STIM1 202764_at Hs.74597 stromal interaction molecule 1 -1.4 -1.9 UNC84B 212144_at Hs.406612 unc-84 homolog A (C. elegans) -3.8 -1.5 DNAH9 210345_s_at Hs.284259 dynein, axonemal, heavy polypeptide 9 1.5 1.6 -1.7 DLGAP4 202570_s_at Hs.177425 disks large associated protein 4 1.0 -3.2 2.2 DOK1 216835_s_at Hs.103854 docking protein 1, 62kDa -1.4 -1.6 -1.6 PDPK1 32029_at Hs.154729 3-phosphoinositide dependent protein kinase-1 1.3 -1.6 PRKAR2A 204842_x_at Hs.365523 protein kinase, cAMP-dependent, regulatory, type II, α 1.2 -1.8 TLR6 207446_at Hs.227105 toll-like receptor 6 -1.3 -1.7 CIB1 201953_at Hs.10803 calcium and integrin binding 1 (calmyrin) -1.9 -1.8 CRSP3 218846_at Hs.29679 cofactor required for Sp1 transcriptional activation, 3 -1.4 -1.7 H2AFX 205436_s_at Hs.147097 H2A histone family, member X -1.2 -1.8 NSEP1 208628_s_at Hs.74497 nuclease sensitive element binding protein 1 -1.2 -1.7 -1.6 MBTPS1 201620_at Hs.75890 membrane-bound transcription factor protease, site 1 -1.4 -1.6 RNPC1 212430_at Hs.236361 RNA-binding region (RNP1, RRM) containing 1 1.4 -1.7 SNRPG 205644_s_at Hs.77496 small nuclear ribonucleoprotein polypeptide G -1.4 -1.5 1.6 THG-1 208104_s_at Hs.102447 TSC-22-like -1.3 -1.6 -1.9 ZBTB7 222082_at Hs.104640 zinc finger and BTB domain containing 7 1.4 -1.8 ZNF281 218401_s_at Hs.59757 zinc finger protein 281 1.1 -1.8 -1.5 ZNF36 214670_at Hs.356344 zinc finger protein 36 (KOX 18) -1.2 -1.6 CASC3 207842_s_at Hs.83422 cancer susceptibility candidate 3 -5.9 -1.6 2.1 C14orf147 212460_at Hs.353161 chromosome 14 open reading frame 147 2.3 1.8 -1.9 C21orf66 218515_at Hs.283771 chromosome 21 open reading frame 66 -1.0 -1.7 FLJ20502 218351_at Hs.23956 hypothetical protein FLJ20502 -1.3 -1.6 -1.6 FLJ20559 219147_s_at Hs.98135 hypothetical protein FLJ20559 -1.0 -1.7 FLJ20989 218187_s_at Hs.169615 hypothetical protein FLJ20989 1.3 -3.7 FLJ21588 215684_s_at Hs.334686 ASC-1 complex subunit P100 -1.0 -1.8 -1.7 FLJ22169 202492_at Hs.323363 hypothetical protein FLJ22169 -1.0 -1.6 GL004 219137_s_at Hs.7045 GL004 protein -1.0 -1.6 -1.7 KIAA0140 203206_at Hs.156016 KIAA0140 gene product -1.4 1.6 -1.5 KIAA0143 212149_at Hs.84087 KIAA0143 protein 1.1 -1.5 KIAA0191 212704_at Hs.12413 KIAA0191 protein 1.1 -1.8 -1.6 KIAA0853 212402_at Hs.136102 KIAA0853 protein -1.8 -1.5 KIAA0930 217118_s_at Hs.13255 KIAA0930 protein -1.0 -1.8 -1.7 KIAA1240 213387_at Hs.62576 KIAA1240 protein 1.3 -1.5 -1.7 KIAA1466 222139_at Hs.147710 KIAA1466 protein -1.1 -1.7 -1.7 LIN7C 219399_at Hs.91393 lin-7 homolog C (C. elegans) 1.5 -2.0 LOC54499 208715_at Hs.93832 putative membrane protein 1.5 -1.7 -1.6 LOC56267 209472_at Hs.180378 hypothetical protein 669 1.2 -1.6 LUC7L2 220099_s_at Hs.7194 LUC7-like 2 (S. cerevisiae) -1.1 -1.5 MGC17528 212615_at Hs.8182 hypothetical protein MGC17528 -1.1 -1.6 1.7 PC326 217908_s_at Hs.279882 PC326 protein -1.7 -1.7 PRO2037 220702_at Hs.283067 hypothetical protein PRO2037 -1.1 -1.5 2.1 --- 213694_at Hs.425559 Homo sapiens mRNA; cDNA DKFZp566L033 1.2 -1.6 -1.5 --- 215063_x_at Hs.283862 Homo sapiens mRNA; cDNA DKFZp547B026 1.5 -1.6 --- 215963_x_at Hs.381031 ESTs, Weakly similar to S34195 ribosomal protein L3 -1.1 -1.5 --- 217336_at ------1.0 -1.8 --- 211074_at ------1.0 -1.7 1.5 1.7 1.5 --- 221419_s_at ------1.3 -1.7

56 --- 217436_x_at ------1.6 -1.9 -1.5 1.9

Genes were identified as differentially expressed as compared to unstimulated neutrophils if 1) genes were called “Present” by MAS5 (Affymetrix) in 2 of 3 individuals tested, 2) average fold-change in gene expression was at least 1.5-fold for A. phagocytophilum-stimulated PMNs and/or 2.0-fold for those stimulated with S. aureus, and 3) genes were significantly increased or decreased at the level of P ≤ 0.05

(unpaired Student’s t-test, red or green text) in one of the times or treatments.