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Compilation of AD-Associated and Non-AD Genes

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Compilation of AD-associated and non-AD genes AD-associated (positives) and non-AD (positives) genes are needed to build a machine learning model. First of all, we performed intensive hand-curation to identify confident AD-associated genes (positives) from various disease genes resources, including AlzGene1, AlzBase2, OMIM3, DisGenet4, DistiLD5, and UniProt6, Open Targets7, GWAS Catalog8, differentially expressed genes (DEGs) in ROSMAP9, and published literature. The curated genes from each resource as well as the corresponding criteria were provided in Table 1 in this file. As the AD-associated genes as well as their reliability vary across these resources, we used a vote strategy and selected only the genes that are present in at least two of the above-described resources to ensure higher reliability. In this way, we collected 147 AD-associated genes (Table 2). Of them, most (n=103, 70%) were associated with AD based on GWAS. Next, we selected a set of non-AD genes, (i.e. negatives), which refer to the genes that have no or minimal association with AD. The main idea of our method for non-AD gene selection was to remove any genes that exhibit potential associations with AD. Let Gp be the set of the 147 collected positives. We then selected a negative gene set GN containing genes that are potentially associated with AD in the following procedure. We first performed a Gene Ontology (GO) enrichment analysis for the positives using PANTHER10 and obtained 737 biological process terms (FDR<0.05). It is reasonable to assume that the genes annotated to these GO terms exhibit a potential association with AD compared with a random baseline because they were annotated to the same GO terms (functions) as the positive genes. In addition, we also collected genes that showed any potential association with AD from the above-described resources. These genes were then combined with the genes annotated to the GO terms, forming a set of genes of potential association with AD, denoted by GS. Next, the negative gene set was then calculated as GN = GA - GS, where GA represents all the genes in the network. By removing the 19471 genes identified in GS from GA (21122 genes), 1651 genes that were not associated with AD were identified and used as non-AD (negatives) genes. Table 1. Resources for compiling AD-associated genes. No. of Resources Genes Filtering Criteria genes PSEN2, HFE, NOS3, PLAU, CALHM1, A2M, PSEN1, OMIM3 All genes associated with AD 12 ADAM10, MPO, ABCA7, APOE, APP APOC1, BCL3, MS4A4A, FRMD4A, GAB2, MTHFD1L, CR1, EPHA1, CLU, PICALM, Genome-wide significant association DistiLD5 19 SORL1, CD33, ABCA7, with AD (p-value < 5.0×10-8) CEACAM16, GLIS3, CD2AP, SRRM4, BCHE, ZNF292 CLU, TNK1, APOE, SOAT1, PVRL2, TRAK2, CHRNB2, TFAM, CTSD, IL33, THRA, IL1RN, IL10, PICALM, STH, IL6, CD33, TFCP2, VLDLR, SORCS1, IL1B, GAB2, ABCA1, CTNNA3, APOC2, IL1A, BIN1, DAPK1, PON1, CST3, CCR2, The top ranked AD genes provided AlzGene11 GAPDHS, IL8, GRN, ECE1, 68 on the AlzGene website. OLR1, TF, LPL, LRP1, HHEX, GAPDH, LDLR, OTC, ARID5B, TNF, TOMM40, EXOC3L2, PGBD1, PRNP, BCAM, CALHM1, UBQLN1, PCK1, NEDD9, SORL1, ADAM10, MME, ENTPD7, FAS, CH25H, APOC1, ACE, CYP19A1, NCAPD2, MTHFR, APOC4, CHAT, CR1 APP, PSEN1, PSEN2, MAPT, APOE, TREM2, PLD3, SORL1, NOTCH3, CLU, PICALM, CR1, ABCA7, BIN1, CD33, CD2AP, MS4A6A, MS4A4E, NME8, Top ranked genes supported by AlzBase2 32 EPHA1, PTK2B, SLC24A4, genetic evidences CELF1, FERMT2, ZCWPW1, INPP5D, HLA-DRB1, HLA- DRB5, MEF2C, TP53INP1, CASS4, IGHV1-67 PSEN1, APP, PSEN2, APOE, Genes associated with AD and score DisGenet12 SORL1, MAPT, BDNF, IL1B, 12 > 0.3 BACE1, ACE, GSK3B, PLAU ADAM10, APOE, APP, MT-ND1, UniProt 6 MT-ND2, PSEN1, PSEN2, All genes associated with AD 8 SORL1 SLC30A6(ZNT6)13, 14, SLC30A4(ZNT4)13, 14, MAOB15, 16, CHRNA717, 18, IGF119, 20, VEGFA21, 22, ARC23, 24, PPARG25, 26, BCL227, 28, 29, IGF2R30, CASP331, 32, NECTIN2 (PVRL2)33, 34, 35, IGF230, 36, 37, VSNL138, 39, ACHE40, 41, 42, CYP46A143, 44, 45, IDE46, 47, 1. For GWAS studies: p- NPY48, 49, 50, IGF1R20, 51, value<5.0×10-8 Published PM20D152, APBB253, 54, ESR155, 2. For differential gene expression 56 literature 56, 57, PAXIP158, 59, CRH60, 61, studies on AD, the gene which is SOD262, 63, 64, SLC2A465, 66, differentially expressed in at least HMOX167, 68, DPYSL269, 70, two studies were included. INSR71, 72, DHCR2473, 74, 75, RELN76, 77, 78, 79, 80, BAX81, 82, 83, REST84, MEOX285, 86, EIF2AK387, 88, MAN2A189, 90, (ABI3, PLCG2)91, 92, DSG226, 93, MS4A294, 95,PPP1R3796, RELB33, 97, TREML298, (HESX1, ADAMTS4, CLNK, HS3ST1, CNTNAP2, ADAM10, APH1B, KAT8, ABI3, ALPK2, ECHDC3, SCIMP, SUZ12P1)99 p-value<5.0×10-8; from both GWAS- GWAS reported and GWAS-mapped genes 265 catalog https://www.ebi.ac.uk/gwas as provided in the GWAS catalog database. Open Genes with association score with AD 175 Targets7 https://www.opentargets.org/ > 0.5 ROSMAP See ref9 All DEGs with FDR<0.05 2614 Table 2. The list of 147 AD-associated genes. AD-associated genes APOE, SORL1, GAB2, CR1, PICALM, CLU, CD33, ABCA7, ADAM10, CD2AP, BIN1, APOC1, TOMM40, INPP5D, PSEN2, EPHA1, APP, MTHFD1L, CNTNAP2, HLA-DRB1, CASS4, BCAM, ABCA1, PTK2B, MS4A6A, FRMD4A, BCL3, SLC24A4, GLIS3, FERMT2, PSEN1, TREM2, ZCWPW1, EXOC3L2, MS4A4A, ACE, APOC4, BZW2, SUCLG2, APOB, SCIMP, SCARB1, RELB, CRY2, PVRL2, CLASRP, ADAMTS4, MMP3, UBE2L3, PPP1R37, ECHDC3, TCF7L2, IL6R, MS4A2, LIPG, MAN2A1, MAPT, ALDH1A2, ABI3, LILRA5, CELF1, PLCG2, HMGCR, OARD1, APH1B, APOC2, OR4S1, STAT4, MS4A4E, PVR, MT-ND2, HS3ST1, CCR2, VASP, CYP8B1, BLOC1S3, PPP1R13L, NFIC, NKPD1, INSR, CNTNAP5, BCAS3, BCHE, BCL2, NME8, CLPTM1, CLNK, UBQLN1, CLMN, IL1B, TRAPPC6A, VSNL1, SORCS1, PPARG, IGSF23, CRH, PSMA1, CHRNB2, FBXL7, CHRNA7, SPON1, MYO16, CHRNA2, VLDLR, KIR3DL2, KIT, HLA-DRB5, BACE1, HLA- DRA, DSG2, CALHM1, RBFOX1, HFE, PILRA, LRP4, HARBI1, TFCP2, CBLC, DPP10, SYNJ1, CDC25B, ACP2, ACHE, PACSIN3, MADD, ZNF652, GSK3B, PFDN1, RIN3, MARK4, GRIN2A, PDGFRB, MAPK8IP1, GRIN3B, CCRL2, ECE1, SCN1A, HBEGF, CACNA1G, CEACAM16, MMP13, ESR1, ALDH5A1, PLAU, SCN8A, CACNA2D1, MMP12 References 1. 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    Supplementary Table S2. DNA microarray dataset of top 30 differentially expressed genes and housekeeping genes Up-regulated in SI cancer cells Symbol Description Cy5_LG Cy3_MI Ratio(Cy3/Cy5) C9orf135 Uncharacterized protein C9orf135 1.37 307.8 224.3 KIAA1245 Notch homolog 2 N-terminal like protein 1.82 406.8 223.6 APITD1 Centromere protein S (CENP-S) 2.56 560.3 218.7 PPIL6 Peptidyl-prolyl cis-trans isomerase-like 6 1.85 343.0 185.7 MYCBP2 Probable E3 ubiquitin-protein ligase MYCBP2 2.01 332.1 165.6 ANGPTL4 Angiopoietin-related protein 4 precursor 10.26 1500.1 146.3 C10orf79 Novel protein (Fragment) 2.86 415.5 145.5 NP_653323.1 KPL2 protein isoform 2 1.82 257.5 141.6 ZNF345 Zinc finger protein 345 1.58 215.7 136.8 SIX1 Homeobox protein SIX1 1.59 216.1 136.0 KLHL7 Kelch-like protein 7 1.91 254.4 133.3 TBX1 T-box transcription factor TBX1 1.57 209.0 133.1 PAG1 Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 2.19 290.9 133.0 NOL12 Nucleolar protein 12 1.61 203.7 126.5 ZNF606 Zinc finger protein 606 2.12 267.7 126.0 NFKBIE NF-kappa-B inhibitor epsilon 5.28 658.3 124.7 ZMYND10 Zinc finger MYND domain-containing protein 10 6.85 835.5 121.9 hCG_23177 - 14.94 1758.9 117.7 KIF3A Kinesin-like protein KIF3A 1.94 224.9 116.1 Q9C0K3_HUMAN Actin-related protein Arp11 3.38 368.0 108.9 NP_056263.1 DPCD protein 2.61 270.5 103.7 GBP1 Interferon-induced guanylate-binding protein 1 1.46 149.1 102.3 NP_660151.2 NAD(P) dependent steroid dehydrogenase-like 1.35 137.4 101.5 NP_689672.2 CDNA FLJ90761 fis, clone THYRO1000099 3.68 372.5
  • Technical Note, Appendix: an Analysis of Blood Processing Methods to Prepare Samples for Genechip® Expression Profiling (Pdf, 1

    Technical Note, Appendix: an Analysis of Blood Processing Methods to Prepare Samples for Genechip® Expression Profiling (Pdf, 1

    Appendix 1: Signature genes for different blood cell types. Blood Cell Type Source Probe Set Description Symbol Blood Cell Type Source Probe Set Description Symbol Fraction ID Fraction ID Mono- Lympho- GSK 203547_at CD4 antigen (p55) CD4 Whitney et al. 209813_x_at T cell receptor TRG nuclear cytes gamma locus cells Whitney et al. 209995_s_at T-cell leukemia/ TCL1A Whitney et al. 203104_at colony stimulating CSF1R lymphoma 1A factor 1 receptor, Whitney et al. 210164_at granzyme B GZMB formerly McDonough (granzyme 2, feline sarcoma viral cytotoxic T-lymphocyte- (v-fms) oncogene associated serine homolog esterase 1) Whitney et al. 203290_at major histocompatibility HLA-DQA1 Whitney et al. 210321_at similar to granzyme B CTLA1 complex, class II, (granzyme 2, cytotoxic DQ alpha 1 T-lymphocyte-associated Whitney et al. 203413_at NEL-like 2 (chicken) NELL2 serine esterase 1) Whitney et al. 203828_s_at natural killer cell NK4 (H. sapiens) transcript 4 Whitney et al. 212827_at immunoglobulin heavy IGHM Whitney et al. 203932_at major histocompatibility HLA-DMB constant mu complex, class II, Whitney et al. 212998_x_at major histocompatibility HLA-DQB1 DM beta complex, class II, Whitney et al. 204655_at chemokine (C-C motif) CCL5 DQ beta 1 ligand 5 Whitney et al. 212999_x_at major histocompatibility HLA-DQB Whitney et al. 204661_at CDW52 antigen CDW52 complex, class II, (CAMPATH-1 antigen) DQ beta 1 Whitney et al. 205049_s_at CD79A antigen CD79A Whitney et al. 213193_x_at T cell receptor beta locus TRB (immunoglobulin- Whitney et al. 213425_at Homo sapiens cDNA associated alpha) FLJ11441 fis, clone Whitney et al. 205291_at interleukin 2 receptor, IL2RB HEMBA1001323, beta mRNA sequence Whitney et al.
  • Insurance and Advance Pay Test Requisition

    Insurance and Advance Pay Test Requisition

    Insurance and Advance Pay Test Requisition (2021) For Specimen Collection Service, Please Fax this Test Requisition to 1.610.271.6085 Client Services is available Monday through Friday from 8:30 AM to 9:00 PM EST at 1.800.394.4493, option 2 Patient Information Patient Name Patient ID# (if available) Date of Birth Sex designated at birth: 9 Male 9 Female Street address City, State, Zip Mobile phone #1 Other Phone #2 Patient email Language spoken if other than English Test and Specimen Information Consult test list for test code and name Test Code: Test Name: Test Code: Test Name: 9 Check if more than 2 tests are ordered. Additional tests should be checked off within the test list ICD-10 Codes (required for billing insurance): Clinical diagnosis: Age at Initial Presentation: Ancestral Background (check all that apply): 9 African 9 Asian: East 9 Asian: Southeast 9 Central/South American 9 Hispanic 9 Native American 9 Ashkenazi Jewish 9 Asian: Indian 9 Caribbean 9 European 9 Middle Eastern 9 Pacific Islander Other: Indications for genetic testing (please check one): 9 Diagnostic (symptomatic) 9 Predictive (asymptomatic) 9 Prenatal* 9 Carrier 9 Family testing/single site Relationship to Proband: If performed at Athena, provide relative’s accession # . If performed at another lab, a copy of the relative’s report is required. Please attach detailed medical records and family history information Specimen Type: Date sample obtained: __________ /__________ /__________ 9 Whole Blood 9 Serum 9 CSF 9 Muscle 9 CVS: Cultured 9 Amniotic Fluid: Cultured 9 Saliva (Not available for all tests) 9 DNA** - tissue source: Concentration ug/ml Was DNA extracted at a CLIA-certified laboratory or a laboratory meeting equivalent requirements (as determined by CAP and/or CMS)? 9 Yes 9 No 9 Other*: If not collected same day as shipped, how was sample stored? 9 Room temp 9 Refrigerated 9 Frozen (-20) 9 Frozen (-80) History of blood transfusion? 9 Yes 9 No Most recent transfusion: __________ /__________ /__________ *Please contact us at 1.800.394.4493, option 2 prior to sending specimens.