Supplementary Document:

Drug- Modeling in Pediatric T-Cell Acute Lymphoblastic Leukemia Highlights Importance of 6-Mercaptopurine for

Outcome.

Alex H Beesley1, Martin J Firth2, Denise Anderson2, Amy L Samuels1, Jette Ford1 and Ursula R Kees1.

Division of Children’s Leukaemia and Cancer Research1 and Division of Bioinformatics and Biostatistics2, Telethon Institute for Child Health

Research, Centre for Child Health Research, University of Western Australia, Perth, Australia.

1 Supplementary Tables

Table S1 – Top 50 Correlating Probes For Each Drug Used in the 10 Drug Model.

Drug Probe Set Gene Symbol Description Correlation Cytoband 6MP 201384_s_at LOC100133166 /// similar to neighbor of BRCA1 gene 1 /// neighbor of 0.868 17q21.31 NBR1 BRCA1 gene 1 6MP 201383_s_at LOC100133166 /// similar to neighbor of BRCA1 gene 1 /// neighbor of 0.848 17q21.31 NBR1 BRCA1 gene 1 6MP 213180_s_at GOSR2 golgi SNAP receptor complex member 2 0.837 17q21 6MP 205355_at ACADSB acyl-Coenzyme A dehydrogenase, short/branched chain 0.835 10q26.13 6MP 203644_s_at MON1B MON1 homolog B (yeast) 0.828 16q23.1 6MP 218352_at RCBTB1 regulator of condensation (RCC1) and BTB 0.811 13q14 (POZ) domain containing 1 6MP 214140_at SLC25A16 solute carrier family 25 (mitochondrial carrier; Graves 0.799 10q21.3 disease autoantigen), member 16 6MP 219734_at SIDT1 SID1 transmembrane family, member 1 0.795 3q13.2 6MP 204067_at SUOX sulfite oxidase 0.793 12q13.2 6MP 207223_s_at ROD1 ROD1 regulator of differentiation 1 (S. pombe) 0.778 9q32 6MP 202131_s_at RIOK3 RIO kinase 3 (yeast) 0.774 18q11.2 6MP 203353_s_at MBD1 methyl-CpG binding domain protein 1 0.773 18q21 6MP 204568_at KIAA0831 KIAA0831 0.772 14q22.3 6MP 202129_s_at RIOK3 RIO kinase 3 (yeast) 0.763 18q11.2 6MP 213572_s_at SERPINB1 serpin peptidase inhibitor, clade B (ovalbumin), member 1 0.747 6p25 6MP 209155_s_at NT5C2 5'-nucleotidase, cytosolic II 0.737 10q24.32-q24.33 6MP 202663_at WIPF1 WAS/WASL interacting protein family, member 1 0.735 2q31.1 6MP 202804_at ABCC1 ATP-binding cassette, sub-family C (CFTR/MRP), 0.731 16p13.1 member 1 6MP 216812_at ------0.732 --- 6MP 217768_at C14orf166 chromosome 14 open reading frame 166 -0.733 14q22.1 6MP 219800_s_at THNSL1 threonine synthase-like 1 (S. cerevisiae) -0.737 10p12.1

2 6MP 217366_at CTNNA1 catenin (cadherin-associated protein), alpha 1, 102kDa -0.739 5q31 6MP 220062_s_at MAGEC2 melanoma antigen family C, 2 -0.740 Xq27 6MP 215298_at ------0.742 --- 6MP 207320_x_at STAU1 staufen, RNA binding protein, homolog 1 (Drosophila) -0.743 20q13.1 6MP 222052_at C19orf54 chromosome 19 open reading frame 54 -0.743 19q13.2 6MP 219909_at MMP28 matrix metallopeptidase 28 -0.744 17q11-q21.1 6MP 201764_at TMEM106C transmembrane protein 106C -0.745 12q13.1 6MP 214104_at GPR161 G protein-coupled receptor 161 -0.750 1q24.2 6MP 215471_s_at MAP7 microtubule-associated protein 7 -0.751 6q23.3 6MP 210212_x_at LOC100133946 /// similar to mature T-cell proliferations 1 /// mature T-cell -0.753 Xq28 MTCP1 proliferation 1 6MP 219569_s_at TMEM22 transmembrane protein 22 -0.753 3q22.3 6MP 216428_x_at KIR3DX1 killer cell immunoglobulin-like receptor, three domains, -0.758 19q13.42 X1 6MP 220437_at LOC55908 hepatocellular carcinoma-associated gene TD26 -0.759 19p13.2 6MP 209747_at TGFB3 transforming growth factor, beta 3 -0.760 14q24 6MP 220003_at LRRC36 leucine rich repeat containing 36 -0.760 16q22.1 6MP 221157_s_at FBXO24 F-box protein 24 -0.760 7q22 6MP 218075_at AAAS achalasia, adrenocortical insufficiency, alacrimia -0.761 12q13 (Allgrove, triple-A) 6MP 207617_at DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked -0.763 Xp11.3-p11.23 6MP 211441_x_at CYP3A43 cytochrome P450, family 3, subfamily A, polypeptide 43 -0.763 7q21.1 6MP 211431_s_at TYRO3 TYRO3 protein tyrosine kinase -0.766 15q15.1-q21.1 6MP 213651_at INPP5J inositol polyphosphate-5-phosphatase J -0.771 22q11.2-q13.2 6MP 217385_at ------0.771 --- 6MP 202276_at SHFM1 split hand/foot malformation (ectrodactyly) type 1 -0.774 7q21.3-q22.1 6MP 220993_s_at GPR63 G protein-coupled receptor 63 -0.776 6q16.1-q16.3 6MP 213037_x_at STAU1 staufen, RNA binding protein, homolog 1 (Drosophila) -0.784 20q13.1 6MP 215506_s_at DIRAS3 DIRAS family, GTP-binding RAS-like 3 -0.798 1p31 6MP 208098_at OR12D3 /// OR5V1 olfactory receptor, family 12, subfamily D, member 3 /// -0.807 6p22.1 olfactory receptor, family 5, subfamily V, member 1 6MP 216659_at LOC1720 dihydrofolate reductase pseudogene -0.807 2p12 6MP 216619_at GTPBP10 GTP-binding protein 10 (putative) (GTPBP10), transcript -0.856 7q21.13

3 variant 2, mRNA 6TG 204067_at SUOX sulfite oxidase 0.915 12q13.2 6TG 215399_s_at OS9 amplified in osteosarcoma 0.888 12q13 6TG 1729_at TRADD TNFRSF1A-associated via death domain 0.879 16q22 6TG 200743_s_at TPP1 tripeptidyl peptidase I 0.862 11p15 6TG 205639_at AOAH acyloxyacyl hydrolase (neutrophil) 0.840 7p14-p12 6TG 210140_at CST7 cystatin F (leukocystatin) 0.838 20p11.21 6TG 213501_at ACOX1 acyl-Coenzyme A oxidase 1, palmitoyl 0.834 17q24-q25|17q25.1 6TG 204085_s_at CLN5 ceroid-lipofuscinosis, neuronal 5 0.831 13q21.1-q32 6TG 216749_at ------0.827 --- 6TG 208499_s_at DNAJC3 DnaJ (Hsp40) homolog, subfamily C, member 3 0.826 13q32 6TG 218130_at C17orf62 chromosome 17 open reading frame 62 0.825 17q25.3 6TG 200742_s_at TPP1 tripeptidyl peptidase I 0.824 11p15 6TG 205419_at GPR183 G protein-coupled receptor 183 0.822 13q32.3 6TG 213485_s_at ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), 0.821 6p21.1 member 10 6TG 213733_at MYO1F myosin IF 0.821 19p13.3-p13.2 6TG 206342_x_at IDS iduronate 2-sulfatase 0.820 Xq28 6TG 210946_at PPAP2A phosphatidic acid phosphatase type 2A 0.820 5q11 6TG 214196_s_at TPP1 tripeptidyl peptidase I 0.815 11p15 6TG 212144_at UNC84B unc-84 homolog B (C. elegans) 0.814 22q13.1 6TG 204655_at CCL5 chemokine (C-C motif) ligand 5 0.813 17q11.2-q12 6TG 203988_s_at FUT8 fucosyltransferase 8 (alpha (1,6) fucosyltransferase) 0.812 14q24.3 6TG 212777_at SOS1 son of sevenless homolog 1 (Drosophila) 0.811 2p22-p21 6TG 221491_x_at HLA-DRB1 /// HLA- major histocompatibility complex, class II, DR beta 1 /// 0.811 14q24-q31 /// DRB2 /// HLA-DRB3 major histocompatibility complex, class II, DR beta 2 19q13.43 /// 6p21.3 /// HLA-DRB4 /// (pseudogene) /// major histocompatibility complex, class HLA-DRB5 II, DR beta 3 /// major histocompatibility complex, class II, DR beta 4 /// major histocompatibility complex, class II, DR beta 5 6TG 212961_x_at CXorf40A /// chromosome X open reading frame 40A /// chromosome X 0.809 Xq28 CXorf40B open reading frame 40B 6TG 222239_s_at INTS6 integrator complex subunit 6 0.808 13q14.12-q14.2

4 6TG 212184_s_at MAP3K7IP2 mitogen-activated protein kinase kinase kinase 7 0.805 6q25.1-q25.3 interacting protein 2 6TG 209147_s_at PPAP2A phosphatidic acid phosphatase type 2A 0.804 5q11 6TG 201444_s_at ATP6AP2 ATPase, H+ transporting, lysosomal accessory protein 2 0.803 Xp11.4 6TG 214696_at C17orf91 chromosome 17 open reading frame 91 0.803 17p13.3 6TG 218571_s_at CHMP4A chromatin modifying protein 4A 0.803 14q12 6TG 210743_s_at CDC14A CDC14 cell division cycle 14 homolog A (S. cerevisiae) 0.801 1p21 6TG 218193_s_at GOLT1B golgi transport 1 homolog B (S. cerevisiae) 0.801 12p12.1 6TG 205926_at IL27RA interleukin 27 receptor, alpha 0.800 19p13.11 6TG 200620_at TMEM59 transmembrane protein 59 0.799 1p36-p31 6TG 200796_s_at MCL1 myeloid cell leukemia sequence 1 (BCL2-related) 0.799 1q21 6TG 215723_s_at PLD1 phospholipase D1, phosphatidylcholine-specific 0.799 3q26 6TG 201920_at SLC20A1 solute carrier family 20 (phosphate transporter), member 1 0.797 2q11-q14 6TG 206195_x_at GH2 growth hormone 2 -0.798 17q24.2 6TG 217904_s_at BACE1 beta-site APP-cleaving enzyme 1 -0.798 11q23.2-q23.3 6TG 206573_at KCNQ3 potassium voltage-gated channel, KQT-like subfamily, -0.799 8q24 member 3 6TG 220698_at MGC4294 hypothetical protein MGC4294 -0.800 20q13.32 6TG 215755_at ------0.802 --- 6TG 216699_s_at KLK1 kallikrein 1 -0.805 19q13.3 6TG 204756_at MAP2K5 mitogen-activated protein kinase kinase 5 -0.806 15q23 6TG 219264_s_at LOC100134089 /// similar to protein phosphatase 2 (formerly 2A), regulatory -0.809 Xp22.33; Yp11.3 PPP2R3B subunit B, beta /// protein phosphatase 2 (formerly 2A), regulatory subunit B'', beta 6TG 218080_x_at FAF1 Fas (TNFRSF6) associated factor 1 -0.816 1p33 6TG 209014_at MAGED1 melanoma antigen family D, 1 -0.817 Xp11.23 6TG 217589_at RAB40A RAB40A, member RAS oncogene family -0.818 Xq22.1 6TG 203446_s_at OCRL oculocerebrorenal syndrome of Lowe -0.821 Xq25-q26.1 6TG 204763_s_at GNAO1 guanine nucleotide binding protein (G protein), alpha -0.902 16q13 activating activity polypeptide O ARAC 202767_at ACP2 acid phosphatase 2, lysosomal 0.881 11p11.2- p11.11|11p12-p11 ARAC 208315_x_at TRAF3 TNF receptor-associated factor 3 0.845 14q32.32

5 ARAC 202495_at TBCC tubulin folding cofactor C 0.843 6pter-p12.1 ARAC 209215_at MFSD10 major facilitator superfamily domain containing 10 0.822 4p16.3 ARAC 212342_at YIPF6 Yip1 domain family, member 6 0.807 Xq12 ARAC 215185_at ------0.800 --- ARAC 43544_at MED16 mediator complex subunit 16 0.784 19p13.3 ARAC 217790_s_at SSR3 signal sequence receptor, gamma (translocon-associated 0.783 3q25.31 protein gamma) ARAC 221545_x_at MED16 mediator complex subunit 16 0.776 19p13.3 ARAC 204149_s_at GSTM4 glutathione S-transferase mu 4 0.775 1p13.3 ARAC 207460_at GZMM granzyme M (lymphocyte met-ase 1) 0.773 19p13.3 ARAC 205078_at PIGF phosphatidylinositol glycan anchor biosynthesis, class F 0.771 2p21-p16 ARAC 207375_s_at IL15RA interleukin 15 receptor, alpha 0.771 10p15-p14 ARAC 33760_at PEX14 peroxisomal biogenesis factor 14 0.771 1p36.22 ARAC 201250_s_at SLC2A1 solute carrier family 2 (facilitated glucose transporter), 0.770 1p35-p31.3 member 1 ARAC 220134_x_at FAM176B family with sequence similarity 176, member B 0.766 1p34.3 ARAC 218282_at EDEM2 ER degradation enhancer, mannosidase alpha-like 2 0.763 20q11.22 ARAC 221218_s_at TPK1 thiamin pyrophosphokinase 1 0.762 7q34-q35 ARAC 210112_at HPS1 Hermansky-Pudlak syndrome 1 0.761 10q23.1-q23.3 ARAC 217881_s_at CDC27 cell division cycle 27 homolog (S. cerevisiae) 0.761 17q12-q23.2 ARAC 221972_s_at SDF4 stromal cell derived factor 4 0.755 1p36.33 ARAC 210321_at GZMH granzyme H (cathepsin G-like 2, protein h-CCPX) 0.754 14q11.2 ARAC 203379_at RPS6KA1 ribosomal protein S6 kinase, 90kDa, polypeptide 1 0.753 1p ARAC 201079_at SYNGR2 synaptogyrin 2 0.749 17q25.3 ARAC 215485_s_at ICAM1 intercellular adhesion molecule 1 0.749 19p13.3-p13.2 ARAC 201078_at TM9SF2 transmembrane 9 superfamily member 2 0.748 13q32.3 ARAC 202121_s_at CHMP2A chromatin modifying protein 2A 0.748 19q ARAC 203057_s_at PRDM2 PR domain containing 2, with ZNF domain 0.745 1p36.21 ARAC 212123_at TCTN3 tectonic family member 3 0.744 10q23.33 ARAC 200681_at GLO1 glyoxalase I 0.743 6p21.3-p21.1 ARAC 213799_s_at PTPRA protein tyrosine phosphatase, receptor type, A 0.743 20p13 ARAC 221648_s_at ------0.740 --- ARAC 217716_s_at SEC61A1 Sec61 alpha 1 subunit (S. cerevisiae) 0.739 3q21.3

6 ARAC 206648_at ZNF571 zinc finger protein 571 -0.739 19q13.12 ARAC 221078_s_at CCDC88A coiled-coil domain containing 88A -0.740 2p16.1 ARAC 211071_s_at MLLT11 myeloid/lymphoid or mixed-lineage leukemia (trithorax -0.746 1q21 homolog, Drosophila); translocated to, 11 ARAC 206700_s_at JARID1D jumonji, AT rich interactive domain 1D -0.751 Yq11|Yq11 ARAC 221507_at TNPO2 transportin 2 -0.758 19p13.13 ARAC 204409_s_at EIF1AY eukaryotic translation initiation factor 1A, Y-linked -0.759 Yq11.222 ARAC 204397_at EML2 echinoderm microtubule associated protein like 2 -0.760 19q13.32 ARAC 201909_at LOC100133662 /// hypothetical protein LOC100133662 /// ribosomal protein -0.769 Yp11.3 RPS4Y1 S4, Y-linked 1 ARAC 221103_s_at WDR52 WD repeat domain 52 -0.773 3q13.2 ARAC 207246_at LOC100130829 /// hypothetical protein LOC100130829 /// zinc finger protein, -0.775 Yp11.3 ZFY Y-linked ARAC 218554_s_at ASH1L ash1 (absent, small, or homeotic)-like (Drosophila) -0.781 1q22 ARAC 207964_x_at IFNA4 interferon, alpha 4 -0.783 9p22 ARAC 210127_at RAB6B RAB6B, member RAS oncogene family -0.789 3q22.1 ARAC 204410_at EIF1AY eukaryotic translation initiation factor 1A, Y-linked -0.802 Yq11.222 ARAC 204763_s_at GNAO1 guanine nucleotide binding protein (G protein), alpha -0.806 16q13 activating activity polypeptide O ARAC 212226_s_at PPAP2B phosphatidic acid phosphatase type 2B -0.818 1pter-p22.1 ARAC 220072_at CSPP1 centrosome and spindle pole associated protein 1 -0.822 8q13.2 DEX 208574_at SOX14 SRY (sex determining region Y)-box 14 0.884 3q22-q23 DEX 200614_at CLTC clathrin, heavy chain (Hc) 0.881 17q11-qter DEX 202433_at SLC35B1 solute carrier family 35, member B1 0.857 17q21.33 DEX 203503_s_at PEX14 peroxisomal biogenesis factor 14 0.856 1p36.22 DEX 208689_s_at RPN2 ribophorin II 0.852 20q12-q13.1 DEX 209503_s_at PSMC5 proteasome (prosome, macropain) 26S subunit, ATPase, 5 0.843 17q23-q25 DEX 213399_x_at RPN2 ribophorin II 0.843 20q12-q13.1 DEX 217039_x_at IGHG1 Immunoglobulin lambda heavy chain 0.839 14q32.33 DEX 208819_at RAB8A RAB8A, member RAS oncogene family 0.828 19p13.1 DEX 221800_s_at C17orf70 chromosome 17 open reading frame 70 0.823 17q25.3 DEX 213491_x_at RPN2 ribophorin II 0.817 20q12-q13.1 DEX 213043_s_at MED24 mediator complex subunit 24 0.813 17q21.1

7 DEX 208803_s_at SRP72 signal recognition particle 72kDa 0.811 4q11 DEX 205331_s_at REEP2 receptor accessory protein 2 0.806 5q31 DEX 201695_s_at NP nucleoside phosphorylase 0.805 14q13.1 DEX 206936_x_at ------0.794 --- DEX 212984_at ATF2 activating transcription factor 2 -0.794 2q32 DEX 222167_at ------0.797 --- DEX 203533_s_at CUL5 cullin 5 -0.798 11q22-q23 DEX 209856_x_at ABI2 abl interactor 2 -0.798 2q33 DEX 211914_x_at NF1 neurofibromin 1 -0.802 17q11.2 DEX 204258_at CHD1 chromodomain helicase DNA binding protein 1 -0.803 5q15-q21 DEX 205559_s_at PCSK5 proprotein convertase subtilisin/kexin type 5 -0.804 9q21.3 DEX 217906_at KLHDC2 kelch domain containing 2 -0.805 14q22.1 DEX 202850_at ABCD3 ATP-binding cassette, sub-family D (ALD), member 3 -0.806 1p22-p21 DEX 205803_s_at TRPC1 transient receptor potential cation channel, subfamily C, -0.807 3q22-q24 member 1 DEX 221103_s_at WDR52 WD repeat domain 52 -0.808 3q13.2 DEX 216557_x_at IGHA1 /// IGHG1 /// immunoglobulin heavy constant alpha 1 /// -0.809 14q32.33 IGHG3 immunoglobulin heavy constant gamma 1 (G1m marker) /// immunoglobulin heavy constant gamma 3 (G3m marker) DEX 212721_at SFRS12 splicing factor, arginine/serine-rich 12 -0.812 5q12.3 DEX 220046_s_at CCNL1 cyclin L1 -0.812 3q25.32 DEX 211565_at SH3GL3 SH3-domain GRB2-like 3 -0.815 15q24 DEX 215221_at ------0.816 --- DEX 208014_x_at RP5-886K2.1 neuronal thread protein AD7c-NTP -0.820 1p36 DEX 54051_at PKNOX1 PBX/knotted 1 homeobox 1 -0.824 21q22.3 DEX 214852_x_at VPS13A vacuolar protein sorting 13 homolog A (S. cerevisiae) -0.826 9q21 DEX 205934_at PLCL1 phospholipase C-like 1 -0.830 2q33 DEX 219700_at PLXDC1 plexin domain containing 1 -0.832 17q21.1 DEX 205802_at TRPC1 transient receptor potential cation channel, subfamily C, -0.834 3q22-q24 member 1 DEX 208046_at HIST1H4A /// histone cluster 1, H4a /// histone cluster 1, H4b /// histone -0.835 12p12.3 /// 1q21 /// HIST1H4B /// cluster 1, H4c /// histone cluster 1, H4d /// histone cluster 6p21.3 /// 6p21.33 ///

8 HIST1H4C /// 1, H4e /// histone cluster 1, H4f /// histone cluster 1, H4h 6p22-p21.3 HIST1H4D /// /// histone cluster 1, H4i /// histone cluster 1, H4j /// histone HIST1H4E cluster 1, H4k /// histone cluster 1, H4l /// histone cluster 2, H4a /// histone cluster 2, H4b DEX 201959_s_at MYCBP2 MYC binding protein 2 -0.836 13q22 DEX 220719_at FLJ13769 hypothetical protein FLJ13769 -0.840 12q24.31 DEX 221155_x_at ------0.841 --- DEX 206790_s_at NDUFB1 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 1, -0.849 14q32.12 7kDa DEX 212080_at MLL Homo sapiens, clone IMAGE:6062880, mRNA -0.849 11q23 DEX 213929_at ------0.851 --- DEX 216624_s_at MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax -0.851 11q23 homolog, Drosophila) DEX 219317_at POLI polymerase (DNA directed) iota -0.858 18q21.1 DEX 212076_at MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax -0.859 11q23 homolog, Drosophila) DEX 203385_at DGKA diacylglycerol kinase, alpha 80kDa -0.863 12q13.3 DEX 215743_at NMT2 N-myristoyltransferase 2 -0.867 10p13 DNR 214183_s_at TKTL1 transketolase-like 1 0.882 Xq28 DNR 201805_at PRKAG1 protein kinase, AMP-activated, gamma 1 non-catalytic 0.859 12q12-q14 subunit DNR 212669_at CAMK2G calcium/calmodulin-dependent protein kinase II gamma 0.840 10q22 DNR 209645_s_at ALDH1B1 aldehyde dehydrogenase 1 family, member B1 0.837 9p11.1 DNR 200947_s_at GLUD1 glutamate dehydrogenase 1 0.835 10q23.3 DNR 200946_x_at GLUD1 glutamate dehydrogenase 1 0.825 10q23.3 DNR 217466_x_at RPS2 ribosomal protein S2 0.823 16p13.3 DNR 203816_at DGUOK deoxyguanosine kinase 0.815 2p13 DNR 217790_s_at SSR3 signal sequence receptor, gamma (translocon-associated 0.809 3q25.31 protein gamma) DNR 216370_s_at TKTL1 transketolase-like 1 0.802 Xq28 DNR 212971_at CARS cysteinyl-tRNA synthetase 0.797 11p15.5 DNR 205472_s_at DACH1 dachshund homolog 1 (Drosophila) 0.795 13q22 DNR 208315_x_at TRAF3 TNF receptor-associated factor 3 0.792 14q32.32

9 DNR 222240_s_at ISYNA1 inositol-3-phosphate synthase 1 0.790 19p13.11 DNR 209199_s_at MEF2C myocyte enhancer factor 2C 0.787 5q14 DNR 215794_x_at GLUD2 glutamate dehydrogenase 2 0.787 Xq24-q25 DNR 220661_s_at ZNF692 zinc finger protein 692 0.786 1q44 DNR 215044_s_at STAM2 signal transducing adaptor molecule (SH3 domain and 0.785 2q23.3 ITAM motif) 2 DNR 208550_x_at KCNG2 potassium voltage-gated channel, subfamily G, member 2 0.781 18q22-q23 DNR 208143_s_at FAM12A family with sequence similarity 12, member A 0.780 14q11.2 DNR 219360_s_at TRPM4 transient receptor potential cation channel, subfamily M, 0.780 19q13.33 member 4 DNR 219888_at SPAG4 sperm associated antigen 4 0.779 20q11.21 DNR 221797_at C17orf90 chromosome 17 open reading frame 90 0.776 17q25.3 DNR 218389_s_at APH1A anterior pharynx defective 1 homolog A (C. elegans) 0.775 1p36.13-q31.3 DNR 203041_s_at LAMP2 lysosomal-associated membrane protein 2 0.773 Xq24 DNR 211578_s_at RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1 0.773 17q23.1 DNR 216167_at LRRN2 leucine rich repeat neuronal 2 0.771 1q32.1 DNR 201767_s_at ELAC2 elaC homolog 2 (E. coli) 0.770 17p11.2 DNR 202402_s_at CARS cysteinyl-tRNA synthetase 0.770 11p15.5 DNR 204833_at ATG12 ATG12 autophagy related 12 homolog (S. cerevisiae) 0.769 5q21-q22 DNR 221081_s_at DENND2D DENN/MADD domain containing 2D -0.770 1p13.3 DNR 208611_s_at SPTAN1 spectrin, alpha, non-erythrocytic 1 (alpha-fodrin) -0.773 9q33-q34 DNR 212583_at AQR aquarius homolog (mouse) -0.773 15q14 DNR 222236_s_at ASAP3 ArfGAP with SH3 domain, ankyrin repeat and PH domain -0.773 1p36.12 3 DNR 34697_at LRP6 low density lipoprotein receptor-related protein 6 -0.774 12p11-p13 DNR 220180_at CCDC68 coiled-coil domain containing 68 -0.778 18q21 DNR 201344_at UBE2D2 ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, -0.779 5q31.2 yeast) DNR 212294_at GNG12 guanine nucleotide binding protein (G protein), gamma 12 -0.782 1p31.3 DNR 216330_s_at POU6F1 POU class 6 homeobox 1 -0.792 12q13.13 DNR 218735_s_at ZNF544 zinc finger protein 544 -0.796 19q13.43 DNR 220940_at ANKRD36B ankyrin repeat domain 36B -0.798 2q11.2 DNR 216066_at ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1 -0.812 9q31.1

10 DNR 206145_at RHAG Rh-associated glycoprotein -0.816 6p21.1-p11 DNR 210968_s_at RTN4 reticulon 4 -0.827 2p16.3 DNR 222368_at ------0.827 --- DNR 202358_s_at SNX19 sorting nexin 19 -0.830 11q25 DNR 215015_at CCDC64 coiled-coil domain containing 64 -0.846 12q24.23 DNR 208406_s_at GRAP2 GRB2-related adaptor protein 2 -0.857 22q13.2 DNR 208191_x_at PSG4 pregnancy specific beta-1-glycoprotein 4 -0.861 19q13.2 DNR 201343_at UBE2D2 ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, -0.865 5q31.2 yeast) DOX 212669_at CAMK2G calcium/calmodulin-dependent protein kinase II gamma 0.773 10q22 DOX 222140_s_at GPR89A /// GPR89B G protein-coupled receptor 89A /// G protein-coupled 0.762 1q21.1 /// GPR89C receptor 89B /// G protein-coupled receptor 89C DOX 209411_s_at GGA3 golgi associated, gamma adaptin ear containing, ARF 0.752 17q25.1 binding protein 3 DOX 217790_s_at SSR3 signal sequence receptor, gamma (translocon-associated 0.749 3q25.31 protein gamma) DOX 220661_s_at ZNF692 zinc finger protein 692 0.744 1q44 DOX 218389_s_at APH1A anterior pharynx defective 1 homolog A (C. elegans) 0.728 1p36.13-q31.3 DOX 214183_s_at TKTL1 transketolase-like 1 0.726 Xq28 DOX 208315_x_at TRAF3 TNF receptor-associated factor 3 0.721 14q32.32 DOX 217268_at RAB7A RAB7A, member RAS oncogene family 0.712 3q21.3 DOX 222240_s_at ISYNA1 inositol-3-phosphate synthase 1 0.711 19p13.11 DOX 43544_at MED16 mediator complex subunit 16 0.708 19p13.3 DOX 201805_at PRKAG1 protein kinase, AMP-activated, gamma 1 non-catalytic 0.703 12q12-q14 subunit DOX 221761_at ADSS adenylosuccinate synthase 0.698 1cen-q12 DOX 217466_x_at RPS2 ribosomal protein S2 0.696 16p13.3 DOX 203816_at DGUOK deoxyguanosine kinase 0.695 2p13 DOX 203629_s_at COG5 component of oligomeric golgi complex 5 0.693 7q22-q31 DOX 212263_at QKI quaking homolog, KH domain RNA binding (mouse) 0.693 6q26|6q26-q27 DOX 204891_s_at LCK lymphocyte-specific protein tyrosine kinase -0.694 1p34.3 DOX 204955_at SRPX sushi-repeat-containing protein, X-linked -0.699 Xp21.1 DOX 217244_at ------0.699 ---

11 DOX 220402_at P53AIP1 p53-regulated apoptosis-inducing protein 1 -0.701 11q24 DOX 216330_s_at POU6F1 POU class 6 homeobox 1 -0.703 12q13.13 DOX 34697_at LRP6 low density lipoprotein receptor-related protein 6 -0.703 12p11-p13 DOX 206137_at RIMS2 regulating synaptic membrane exocytosis 2 -0.704 8q22.3 DOX 220180_at CCDC68 coiled-coil domain containing 68 -0.705 18q21 DOX 201287_s_at SDC1 syndecan 1 -0.708 2p24.1 DOX 210968_s_at RTN4 reticulon 4 -0.708 2p16.3 DOX 215015_at CCDC64 coiled-coil domain containing 64 -0.710 12q24.23 DOX 218634_at PHLDA3 pleckstrin -like domain, family A, member 3 -0.710 1q31 DOX 205606_at LRP6 low density lipoprotein receptor-related protein 6 -0.713 12p11-p13 DOX 210796_x_at SIGLEC6 sialic acid binding Ig-like lectin 6 -0.713 19q13.3 DOX 207964_x_at IFNA4 interferon, alpha 4 -0.717 9p22 DOX 215964_at ------0.718 --- DOX 58780_s_at FLJ10357 hypothetical protein FLJ10357 -0.718 14q11.2 DOX 207664_at ADAM2 ADAM metallopeptidase domain 2 -0.721 8p11.2 DOX 204584_at L1CAM L1 cell adhesion molecule -0.724 Xq28 DOX 212728_at DLG3 discs, large homolog 3 (Drosophila) -0.726 Xq13.1 DOX 201343_at UBE2D2 ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, -0.736 5q31.2 yeast) DOX 206520_x_at SIGLEC6 sialic acid binding Ig-like lectin 6 -0.740 19q13.3 DOX 218394_at ROGDI rogdi homolog (Drosophila) -0.742 16p13.3 DOX 202812_at GAA glucosidase, alpha; acid -0.746 17q25.2-q25.3 DOX 208406_s_at GRAP2 GRB2-related adaptor protein 2 -0.747 22q13.2 DOX 48106_at SLC48A1 solute carrier family 48 (heme transporter), member 1 -0.747 12q13.11 DOX 210854_x_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, -0.751 Xq28 creatine), member 8 DOX 213424_at KIAA0895 KIAA0895 -0.752 7p14.2 DOX 201344_at UBE2D2 ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, -0.756 5q31.2 yeast) DOX 208611_s_at SPTAN1 spectrin, alpha, non-erythrocytic 1 (alpha-fodrin) -0.784 9q33-q34 DOX 222236_s_at ASAP3 ArfGAP with SH3 domain, ankyrin repeat and PH domain -0.796 1p36.12 3 DOX 206343_s_at NRG1 neuregulin 1 -0.797 8p12

12 DOX 206425_s_at TRPC3 transient receptor potential cation channel, subfamily C, -0.816 4q27 member 3 ASP 210672_s_at C16orf35 chromosome 16 open reading frame 35 0.932 16p13.3 ASP 209432_s_at CREB3 cAMP responsive element binding protein 3 0.923 9pter-p22.1 ASP 205146_x_at APBA3 amyloid beta (A4) precursor protein-binding, family A, 0.877 19p13.3 member 3 ASP 221790_s_at LDLRAP1 low density lipoprotein receptor adaptor protein 1 0.874 1p36-p35 ASP 220892_s_at PSAT1 phosphoserine aminotransferase 1 0.866 9q21.2 ASP 51176_at LOC100131612 /// similar to cofactor required for Sp1 transcriptional 0.863 9q34.1-q34.3 MED27 activation, subunit 8, 34kDa /// mediator complex subunit 27 ASP 221665_s_at EPS8L1 EPS8-like 1 0.853 19q13.42 ASP 210534_s_at B9D1 B9 protein domain 1 0.846 17p11.2 ASP 202022_at ALDOC aldolase C, fructose-bisphosphate 0.842 17cen-q12 ASP 200764_s_at CTNNA1 catenin (cadherin-associated protein), alpha 1, 102kDa 0.840 5q31 ASP 202145_at LY6E lymphocyte antigen 6 complex, E 0.840 8q24.3 ASP 209177_at C3orf60 chromosome 3 open reading frame 60 0.839 3p21.31 ASP 208815_x_at HSPA4 heat shock 70kDa protein 4 0.837 5q31.1-q31.2 ASP 218329_at PRDM4 PR domain containing 4 0.837 12q23-q24.1 ASP 218915_at NF2 neurofibromin 2 (merlin) 0.836 22q12.2 ASP 213399_x_at RPN2 ribophorin II 0.835 20q12-q13.1 ASP 209549_s_at DGUOK deoxyguanosine kinase 0.833 2p13 ASP 204247_s_at CDK5 cyclin-dependent kinase 5 0.832 7q36 ASP 212047_s_at RNF167 ring finger protein 167 0.830 17p13.2 ASP 201002_s_at TMEM189-UBE2V1 TMEM189-UBE2V1 readthrough transcript /// ubiquitin- 0.826 20q13.2 /// UBE2V1 conjugating enzyme E2 variant 1 ASP 216326_s_at HDAC3 histone deacetylase 3 0.823 5q31 ASP 202421_at IGSF3 immunoglobulin superfamily, member 3 0.821 1p13 ASP 211017_s_at NF2 neurofibromin 2 (merlin) 0.817 22q12.2 ASP 221146_at ------0.817 --- ASP 202480_s_at DEDD death effector domain containing 0.816 1q23.3 ASP 218568_at AGK acylglycerol kinase 0.816 7q34 ASP 218455_at NFS1 NFS1 nitrogen fixation 1 homolog (S. cerevisiae) 0.815 20q11.22

13 ASP 202343_x_at COX5B cytochrome c oxidase subunit Vb 0.813 2cen-q13 ASP 200949_x_at RPS20 ribosomal protein S20 -0.811 8q12 ASP 206059_at ZNF91 zinc finger protein 91 -0.811 19p13.1-p12 ASP 218518_at FAM13B1 family with sequence similarity 13, member B1 -0.811 5q31 ASP 214988_s_at SON SON DNA binding protein -0.815 21q22.1- q22.2|21q22.11 ASP 201321_s_at SMARCC2 SWI/SNF related, matrix associated, actin dependent -0.816 12q13-q14 regulator of chromatin, subfamily c, member 2 ASP 211442_x_at CYP3A43 cytochrome P450, family 3, subfamily A, polypeptide 43 -0.818 7q21.1 ASP 209936_at RBM5 RNA binding motif protein 5 -0.825 3p21.3 ASP 213788_s_at NCRNA00094 non-protein coding RNA 94 -0.830 9q34 ASP 210312_s_at IFT20 intraflagellar transport 20 homolog (Chlamydomonas) -0.831 17q11.2 ASP 212209_at MED13L mediator complex subunit 13-like -0.831 12q24.21 ASP 201986_at MED13 mediator complex subunit 13 -0.832 17q22-q23 ASP 202050_s_at ZMYM4 zinc finger, MYM-type 4 -0.834 1p32-p34 ASP 208656_s_at CCNI cyclin I -0.837 4q21.1 ASP 213649_at SFRS7 splicing factor, arginine/serine-rich 7, 35kDa -0.839 2p22.1 ASP 206829_x_at ZNF430 zinc finger protein 430 -0.845 19p12 ASP 218312_s_at ZSCAN18 zinc finger and SCAN domain containing 18 -0.847 19q13.43 ASP 206958_s_at UPF3A UPF3 regulator of nonsense transcripts homolog A (yeast) -0.857 13q34 ASP 220085_at HELLS helicase, lymphoid-specific -0.864 10q24.2 ASP 213517_at PCBP2 poly(rC) binding protein 2 -0.879 12q13.12-q13.13 ASP 214929_s_at KIAA1109 KIAA1109 -0.880 4q27 ASP 209259_s_at SMC3 structural maintenance of 3 -0.882 10q25 ASP 217554_at ------0.896 --- MPRED 220773_s_at GPHN gephyrin 0.915 14q23.3 MPRED 208574_at SOX14 SRY (sex determining region Y)-box 14 0.910 3q22-q23 MPRED 212592_at IGJ immunoglobulin J polypeptide, linker protein for 0.905 4q21 immunoglobulin alpha and mu polypeptides MPRED 217871_s_at LOC284889 /// MIF hypothetical protein LOC284889 /// macrophage migration 0.886 22q11.23 inhibitory factor (glycosylation-inhibiting factor) MPRED 216532_x_at LOC728344 similar to hCG1978918 0.878 6p25.2 MPRED 208708_x_at EIF5 eukaryotic translation initiation factor 5 0.876 14q32.32

14 MPRED 203677_s_at TARBP2 TAR (HIV-1) RNA binding protein 2 0.872 12q12-q13 MPRED 213334_x_at TREX2 /// UCHL5IP three prime repair exonuclease 2 /// UCHL5 interacting 0.872 Xq28 protein MPRED 218403_at TRIAP1 TP53 regulated inhibitor of apoptosis 1 0.872 12q24.31 MPRED 210250_x_at ADSL adenylosuccinate lyase 0.866 22q13.1|22q13.2 MPRED 217949_s_at VKORC1 vitamin K epoxide reductase complex, subunit 1 0.865 16p11.2 MPRED 202433_at SLC35B1 solute carrier family 35, member B1 0.860 17q21.33 MPRED 209503_s_at PSMC5 proteasome (prosome, macropain) 26S subunit, ATPase, 5 0.860 17q23-q25 MPRED 209080_x_at GLRX3 glutaredoxin 3 0.859 10q26 MPRED 221932_s_at GLRX5 glutaredoxin 5 0.859 14q32.13 MPRED 201175_at TXNDC14 thioredoxin domain containing 14 0.857 11cen-q22.3 MPRED 207707_s_at SEC13 SEC13 homolog (S. cerevisiae) 0.857 3p25-p24 MPRED 211882_x_at FUT6 fucosyltransferase 6 (alpha (1,3) fucosyltransferase) 0.856 19p13.3 MPRED 210573_s_at POLR3C polymerase (RNA) III (DNA directed) polypeptide C 0.855 1q21.1 (62kD) MPRED 211662_s_at VDAC2 voltage-dependent anion channel 2 0.855 10q22 MPRED 200818_at ATP5O ATP synthase, H+ transporting, mitochondrial F1 0.854 21q22.1- complex, O subunit q22.2|21q22.11 MPRED 202151_s_at UBAC1 UBA domain containing 1 0.854 9q34.3 MPRED 221923_s_at NPM1 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 0.854 5q35 MPRED 213043_s_at MED24 mediator complex subunit 24 0.849 17q21.1 MPRED 218836_at RPP21 /// TRIM39R ribonuclease P/MRP 21kDa subunit /// TRIM39-like 0.849 6p21.33 protein MPRED 209452_s_at VTI1B vesicle transport through interaction with t-SNAREs 0.848 14q24.1 homolog 1B (yeast) MPRED 208996_s_at POLR2C polymerase (RNA) II (DNA directed) polypeptide C, 0.847 16q13-q21 33kDa MPRED 212087_s_at ERAL1 Era G-protein-like 1 (E. coli) 0.846 17q11.2 MPRED 216769_x_at ------0.845 --- MPRED 216858_x_at ------0.846 --- MPRED 212984_at ATF2 activating transcription factor 2 -0.851 2q32 MPRED 212980_at USP34 ubiquitin specific peptidase 34 -0.853 2p15 MPRED 203791_at DMXL1 Dmx-like 1 -0.859 5q22

15 MPRED 206936_x_at ------0.859 --- MPRED AFFX------0.861 --- M27830_5_at MPRED 204516_at ATXN7 ataxin 7 -0.862 3p21.1-p12 MPRED 215063_x_at LRRC40 leucine rich repeat containing 40 -0.863 1p31.1 MPRED AFFX-CreX------0.863 --- 3_at MPRED 212080_at MLL Homo sapiens, clone IMAGE:6062880, mRNA -0.865 11q23 MPRED 220046_s_at CCNL1 cyclin L1 -0.866 3q25.32 MPRED 220719_at FLJ13769 hypothetical protein FLJ13769 -0.868 12q24.31 MPRED 206323_x_at OPHN1 oligophrenin 1 -0.870 Xq12 MPRED 215743_at NMT2 N-myristoyltransferase 2 -0.873 10p13 MPRED 211914_x_at NF1 neurofibromin 1 -0.877 17q11.2 MPRED 210249_s_at NCOA1 nuclear receptor coactivator 1 -0.882 2p23 MPRED 214683_s_at CLK1 CDC-like kinase 1 -0.882 2q33 MPRED 210491_at ------0.889 --- MPRED 216624_s_at MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax -0.893 11q23 homolog, Drosophila) MPRED 212076_at MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax -0.895 11q23 homolog, Drosophila) MPRED 212079_s_at MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax -0.904 11q23 homolog, Drosophila) MTX 209583_s_at CD200 CD200 molecule 0.922 3q12-q13 MTX 209582_s_at CD200 CD200 molecule 0.908 3q12-q13 MTX 205410_s_at ATP2B4 ATPase, Ca++ transporting, plasma membrane 4 0.856 1q32.1 MTX 219234_x_at SCRN3 secernin 3 0.838 2q31.1 MTX 218740_s_at CDK5RAP3 CDK5 regulatory subunit associated protein 3 0.835 17q21.32 MTX 210407_at PPM1A protein phosphatase 1A (formerly 2C), magnesium- 0.832 14q23.1 dependent, alpha isoform MTX 220253_s_at LRP12 low density lipoprotein-related protein 12 0.825 8q22.2-q23.1 MTX 208386_x_at DMC1 DMC1 dosage suppressor of mck1 homolog, meiosis- 0.822 22q13.1 specific homologous recombination (yeast) MTX 220722_s_at SLC5A7 solute carrier family 5 (choline transporter), member 7 0.821 2q12

16 MTX 38069_at CLCN7 chloride channel 7 0.815 16p13 MTX 204307_at KIAA0329 KIAA0329 0.814 14q32.31 MTX 205798_at IL7R interleukin 7 receptor 0.812 5p13 MTX 208382_s_at DMC1 DMC1 dosage suppressor of mck1 homolog, meiosis- 0.810 22q13.1 specific homologous recombination (yeast) MTX 215532_x_at ZNF492 zinc finger protein 492 0.809 19p12 MTX 200626_s_at MATR3 matrin 3 0.808 5q31.2 MTX 215782_at RAB40AL RAB40A, member RAS oncogene family-like 0.807 Xq22.2 MTX 202759_s_at AKAP2 /// PALM2 /// A kinase (PRKA) anchor protein 2 /// paralemmin 2 /// 0.803 9q31-q33 PALM2-AKAP2 PALM2-AKAP2 readthrough transcript MTX 220157_x_at PLEKHA8 /// pleckstrin homology domain containing, family A 0.802 12q /// 7p21-p11.2 PLEKHA9 (phosphoinositide binding specific) member 8 /// pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 9 MTX 204861_s_at NAIP NLR family, apoptosis inhibitory protein 0.800 5q13.1 MTX 214153_at ELOVL5 ELOVL family member 5, elongation of long chain fatty 0.800 6p21.1-p12.1 acids (FEN1/Elo2, SUR4/Elo3-like, yeast) MTX 202760_s_at PALM2-AKAP2 PALM2-AKAP2 readthrough transcript 0.797 9q31-q33 MTX 206545_at CD28 CD28 molecule 0.797 2q33 MTX 217529_at ORAI2 ORAI calcium release-activated calcium modulator 2 0.795 7q22.1 MTX AFFX------0.794 --- M27830_5_at MTX 205674_x_at FXYD2 FXYD domain containing ion transport regulator 2 0.793 11q23 MTX 211861_x_at CD28 CD28 molecule 0.793 2q33 MTX 201085_s_at SON SON DNA binding protein 0.792 21q22.1- q22.2|21q22.11 MTX 207237_at KCNA3 potassium voltage-gated channel, shaker-related subfamily, 0.791 1p13.3 member 3 MTX 219470_x_at CCNJ cyclin J 0.791 10pter-q26.12 MTX 221484_at B4GALT5 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, -0.798 20q13.1-q13.2 polypeptide 5 MTX 203565_s_at MNAT1 menage a trois homolog 1, cyclin H assembly factor -0.800 14q23 (Xenopus laevis) MTX 209095_at DLD dihydrolipoamide dehydrogenase -0.800 7q31-q32 17 MTX 219322_s_at WDR8 WD repeat domain 8 -0.804 1p36.3 MTX 215983_s_at UBXN8 UBX domain protein 8 -0.806 8p12-p11.2 MTX 203925_at GCLM glutamate-cysteine ligase, modifier subunit -0.809 1p22.1 MTX 212175_s_at AK2 adenylate kinase 2 -0.809 1p34 MTX 205195_at AP1S1 adaptor-related protein complex 1, sigma 1 subunit -0.813 7q22.1 MTX 204919_at PRR4 proline rich 4 (lacrimal) -0.815 12p13 MTX 208308_s_at GPI glucose phosphate isomerase -0.818 19q13.1 MTX 219275_at PDCD5 programmed cell death 5 -0.828 19q12-q13.1 MTX 207130_at ZMYND8 zinc finger, MYND-type containing 8 -0.831 20q13.12 MTX 215772_x_at SUCLG2 succinate-CoA ligase, GDP-forming, beta subunit -0.834 3p14.1 MTX 212459_x_at SUCLG2 succinate-CoA ligase, GDP-forming, beta subunit -0.837 3p14.1 MTX 218654_s_at MRPS33 mitochondrial ribosomal protein S33 -0.837 7q32-q34 MTX 203857_s_at PDIA5 protein disulfide isomerase family A, member 5 -0.842 3q21.1 MTX 219053_s_at VPS37C vacuolar protein sorting 37 homolog C (S. cerevisiae) -0.844 11q12.2 MTX 203259_s_at HDDC2 HD domain containing 2 -0.848 6q13-q24.3 MTX 214835_s_at SUCLG2 succinate-CoA ligase, GDP-forming, beta subunit -0.877 3p14.1 MTX 202472_at MPI mannose phosphate isomerase -0.899 15q22-qter MTX 203790_s_at HRSP12 heat-responsive protein 12 -0.904 8q22 VCR 201805_at PRKAG1 protein kinase, AMP-activated, gamma, non-catalytic 0.871 12q12-q14 subunit VCR 212121_at TCTN3 tectonic family member 3 0.852 10q23.33 VCR 220358_at BATF3 basic leucine zipper transcription factor, ATF-like 3 0.849 1q32.3 VCR 210321_at GZMH granzyme H (cathepsin G-like 2, protein h-CCPX) 0.822 14q11.2 VCR 218797_s_at SIRT7 sirtuin (silent mating type information regulation 2 0.822 17q25 homolog) 7 (S. cerevisiae) VCR 205418_at FES feline sarcoma oncogene 0.821 15q26.1 VCR 222239_s_at INTS6 integrator complex subunit 6 0.815 13q14.12-q14.2 VCR 213052_at PRKAR2A Testis mRNA for the RII-alpha subunit of cAMP 0.809 3p21.3-p21.2 dependent protein kinase VCR 204702_s_at NFE2L3 nuclear factor (erythroid-derived 2)-like 3 0.808 7p15-p14 VCR 214786_at MAP3K1 mitogen-activated protein kinase kinase kinase 1 0.808 5q11.2 VCR 205035_at CTDP1 CTD (carboxy-terminal domain, RNA polymerase II, 0.796 18q23 polypeptide A) phosphatase, subunit 1

18 VCR 201410_at PLEKHB2 pleckstrin homology domain containing, family B, member 0.792 2q21.1 2 VCR 213628_at CLCC1 chloride channel CLIC-like 1 0.790 1p13.3 VCR 212669_at CAMK2G calcium/calmodulin-dependent protein kinase II gamma 0.785 10q22 VCR 209338_at TFCP2 transcription factor CP2 0.779 12q13 VCR 213116_at NEK3 NIMA (never in mitosis gene a)-related kinase 3 0.778 13q14.13 VCR 200975_at PPT1 palmitoyl-protein thioesterase 1 0.776 1p32 VCR 201707_at PEX19 peroxisomal biogenesis factor 19 0.776 1q23.2 VCR 214869_x_at GAPVD1 GTPase activating protein and VPS9 domains 1 0.776 9q33.3 VCR 212342_at YIPF6 Yip1 domain family, member 6 0.767 Xq12 VCR 209716_at CSF1 colony stimulating factor 1 (macrophage) 0.766 1p21-p13 VCR 212123_at TCTN3 tectonic family member 3 0.766 10q23.33 VCR 215185_at ------0.765 --- VCR 212024_x_at FLII flightless I homolog (Drosophila) 0.761 17p11.2 VCR 202401_s_at SRF serum response factor (c-fos serum response element- 0.760 6p21.1 binding transcription factor) VCR 202389_s_at HTT huntingtin 0.759 4p16.3 VCR 208838_at CAND1 cullin-associated and neddylation-dissociated 1 -0.760 12q14 VCR 221599_at C11orf67 chromosome 11 open reading frame 67 -0.761 11q14.1 VCR 214629_x_at RTN4 reticulon 4 -0.762 2p16.3 VCR 211071_s_at MLLT11 myeloid/lymphoid or mixed-lineage leukemia (trithorax -0.765 1q21 homolog, Drosophila); translocated to, 11 VCR 212721_at SFRS12 splicing factor, arginine/serine-rich 12 -0.765 5q12.3 VCR 202831_at GPX2 glutathione peroxidase 2 (gastrointestinal) -0.772 14q24.1 VCR 220854_at ------0.775 --- VCR 220977_x_at EPB41L5 erythrocyte membrane protein band 4.1 like 5 -0.775 2q14.2 VCR 213239_at PIBF1 progesterone immunomodulatory binding factor 1 -0.777 13q22.1 VCR 207394_at ZNF137 zinc finger protein 137 -0.778 19q13.4 VCR 217244_at ------0.780 --- VCR 207973_x_at ACRV1 acrosomal vesicle protein 1 -0.781 11q23-q24 VCR 218033_s_at SNN stannin -0.781 16p13 VCR 206195_x_at GH2 growth hormone 2 -0.785 17q24.2 VCR 201225_s_at SRRM1 serine/arginine repetitive matrix 1 -0.792 1p36.11

19 VCR 205705_at ANKRD26 ankyrin repeat domain 26 -0.792 10pter-q22.1 VCR 207073_at CDKL2 cyclin-dependent kinase-like 2 (CDC2-related kinase) -0.794 4q21.1 VCR 206786_at HTN3 histatin 3 -0.798 4q13 VCR 202952_s_at ADAM12 ADAM metallopeptidase domain 12 -0.802 10q26.3 VCR 207605_x_at ZNF117 zinc finger protein 117 -0.821 7q11.21 VCR 204165_at WASF1 WAS protein family, member 1 -0.822 6q21-q22 VCR 217589_at RAB40A RAB40A, member RAS oncogene family -0.822 Xq22.1 VCR 217885_at IPO9 importin 9 -0.822 1q32.1 VCR 205739_x_at ZNF107 zinc finger protein 107 -0.823 7q11.2

20 Table S2 – Drug-Gene Correlations for Associated with Canonical Pathways of Multi-Drug Resistance, Detoxification and Metabolism (light shading p<0.01, dark shading with bold p<0.001).

Gene Symbol Probe ID MPRED DEX ASP MTX DNR DOX ARAC VCR 6MP 6TG ABCB9 214209_s_at 0.490.44 0.76 -0.61 0.27 0.12 0.32 0.29 -0.48 -0.07 ABCC1 202805_s_at -0.35 -0.04 -0.33 0.52 0.19 0.330.17 0.33 0.68 0.74 ABCC1 202804_at -0.08 0.23 -0.10 0.35 0.34 0.420.33 0.60 0.73 0.79 ABCC10 215873_x_at -0.01 0.28 0.22 0.15 0.33 0.290.28 0.66 0.54 0.65 ABCC10 213485_s_at -0.15 0.20 0.19 0.10 0.17 0.180.40 0.54 0.56 0.82 ABCC3 208161_s_at 0.75 0.46 0.41 -0.61 0.32 0.12 0.13 0.03 -0.45 -0.51 ABCC9 208562_s_at 0.14-0.13 0.41 -0.55 -0.17 -0.32-0.19 -0.24 -0.69 -0.56 ABCC9 208561_at 0.71 0.64 0.20 -0.47 0.28 0.26 0.15 0.18 -0.29 -0.22 ABTB2 213497_at -0.47 -0.63 -0.28 0.53 -0.47 -0.44 -0.66 -0.54 -0.01 -0.23 ACLY 210337_s_at 0.75 0.74 0.57 -0.43 0.35 0.24 0.34 0.31 -0.21 0.21 ACLY 201128_s_at 0.80 0.76 0.60 -0.42 0.39 0.27 0.38 0.38 -0.16 0.22 ACLY 201127_s_at 0.72 0.73 0.63 -0.42 0.56 0.39 0.44 0.48 -0.04 0.32 AIF 205512_s_at 0.69 0.57 0.66 -0.54 0.46 0.24 0.30 0.33 -0.22 0.08 AKT2 211453_s_at -0.74 -0.60 -0.40 0.48 -0.37 -0.16 -0.25 -0.34 -0.02 -0.15 AKT3 212609_s_at -0.70 -0.68 -0.41 0.70 -0.30 -0.16 -0.35 -0.20 0.35 -0.05 AKT3 212607_at -0.61 -0.48 -0.22 0.66 -0.31 -0.15 -0.14 -0.10 0.35 0.14 ALDH18A1 217791_s_at 0.75 0.54 0.48 -0.39 0.47 0.34 0.22 0.18 -0.37 -0.26 ALDH1A1 212224_at 0.06 -0.22 0.24 0.04 -0.23 -0.39-0.51 -0.47 -0.56 -0.70 ALDH1A2 207015_s_at -0.28 -0.27 -0.11 0.75 -0.10 -0.01 -0.37 -0.15 0.17 -0.01 ALDH1A2 207016_s_at -0.17 -0.13 0.03 0.64 0.01 0.07 -0.22 -0.03 0.13 0.00 ALDH1B1 209645_s_at 0.350.49 0.36 -0.36 0.84 0.69 0.58 0.65 0.20 0.27 ALDH2 201425_at 0.10-0.38 -0.02 -0.04 -0.51 -0.67 -0.70 -0.71 -0.48 -0.61 ALDH3A1 205623_at 0.44 0.27 0.56 -0.69 0.32 0.11 0.18 0.26 -0.40 -0.20 ALDH3A2 210544_s_at -0.14 -0.20 0.09 0.18 -0.65 -0.66 -0.22 -0.27 0.00 0.02 ALDH3A2 202054_s_at 0.60 0.64 0.50 -0.39 0.22 0.07 0.36 0.47 0.07 0.30 ALDH3B1 211004_s_at -0.58 -0.41 -0.69 0.67 -0.41 -0.20 -0.30 -0.32 0.35 0.05 AOX1 205082_s_at 0.13-0.15 0.13 -0.19 -0.05 -0.11-0.12 -0.10 -0.27 -0.45 AOX1 205083_at 0.250.08 0.20 -0.05 -0.20 -0.16-0.23 -0.22 -0.61 -0.53 ARF 200065_s_at 0.340.50 0.45 -0.63 0.56 0.43 0.71 0.49 0.02 0.44

21 ARF 208750_s_at 0.340.54 0.39 -0.52 0.48 0.40 0.67 0.44 0.09 0.54 ASNS 205047_s_at 0.070.17 0.71 -0.35 0.38 0.27 0.52 0.28 -0.30 0.09 ATR 209902_at 0.03-0.31 -0.31 -0.01 -0.09 -0.13-0.40 -0.37 -0.23 -0.70 ATR 209903_s_at -0.45 -0.59 -0.65 0.59 -0.29 -0.17 -0.50 -0.34 0.24 -0.24 BCL2L11 222343_at 0.65 0.35 0.35 -0.38 0.38 0.17 -0.09 0.04 -0.36 -0.34 BCL2L11 208536_s_at 0.69 0.41 0.26 -0.48 0.28 0.17 0.01 0.08 -0.36 -0.30 BCL2L14 221241_s_at -0.03 -0.31 -0.35 0.36 -0.56 -0.47 -0.71 -0.62 -0.23 -0.44 BID 204493_at 0.400.06 0.02 -0.12 -0.09 -0.19-0.45 -0.35 -0.52 -0.64 BIK 205780_at 0.69 0.46 0.45 -0.28 0.08 -0.13 0.01 -0.03 -0.25 -0.09 BOK 221454_at 0.66 0.46 0.51 -0.64 0.38 0.25 0.29 0.25 -0.40 -0.24 BRCA2 214727_at -0.37 -0.52 -0.43 0.42 -0.57 -0.44 -0.64 -0.59 -0.22 -0.37 BRCA2 208368_s_at -0.50 -0.49 -0.67 0.52 -0.44 -0.26 -0.49 -0.51 0.01 -0.27 CASP4 209310_s_at -0.43 -0.17 -0.67 0.20 -0.11 0.05 0.08 0.06 0.60 0.39 CASP6 211464_x_at -0.57 -0.45 -0.62 0.71 -0.46 -0.23 -0.37 -0.28 0.40 0.09 CASP8 213373_s_at -0.45 -0.14 -0.25 0.17 -0.14 -0.110.16 0.29 0.64 0.55 CASP9 203984_s_at 0.130.41 0.14 -0.35 0.37 0.290.46 0.69 0.42 0.48 CCND1 208711_s_at 0.58 0.69 0.42 -0.54 0.35 0.32 0.65 0.44 -0.02 0.24 CDA 205627_at 0.450.31 0.31 -0.11 0.01 -0.03-0.10 -0.04 -0.30 -0.36 CHEK2 (CHK2) 210416_s_at 0.74 0.64 0.65 -0.55 0.60 0.44 0.46 0.35 -0.38 -0.23 cIAP2 210538_s_at -0.19 0.18 0.08 -0.12 0.19 0.240.44 0.55 0.38 0.66 CYP1A2 207608_x_at -0.61 -0.57 -0.77 0.62 -0.44 -0.25 -0.39 -0.39 0.42 0.09 CYP1B1 202436_s_at -0.18 0.16 0.38 -0.22 0.06 0.070.58 0.46 0.26 0.66 CYP1B1 202437_s_at -0.17 0.18 0.39 -0.22 0.07 0.080.58 0.45 0.23 0.68 CYP1B1 202435_s_at -0.20 0.17 0.37 -0.15 0.07 0.100.59 0.46 0.29 0.71 CYP2A13 216334_s_at 0.330.41 0.28 0.08 0.65 0.56 0.38 0.58 0.44 0.46 CYP2A6 207244_x_at -0.37 -0.62 -0.44 0.21 -0.38 -0.33-0.55 -0.66 -0.27 -0.60 CYP2A6 211295_x_at -0.26 -0.46 -0.64 0.28 -0.60 -0.47 -0.63 -0.55 -0.14 -0.59 CYP2A6 /// CYP2A13 / 207718_x_at -0.45 -0.51 -0.28 0.34 -0.72 -0.56 -0.56 -0.58 -0.28 -0.37 CYP2B6 206755_at -0.53 -0.53 -0.46 0.61 -0.66 -0.41 -0.51 -0.48 -0.01 -0.17 CYP2C19 /// CYP2C9 216661_x_at 0.00 -0.26 -0.34 0.20 -0.32 -0.33 -0.55 -0.39 -0.16 -0.64 CYP2C8 208147_s_at 0.80 0.72 0.38 -0.30 0.33 0.26 0.20 0.20 -0.27 -0.17 CYP2F1 207913_at 0.74 0.55 0.35 -0.58 0.12 0.08 0.21 0.05 -0.48 -0.32 CYP3A4 205999_x_at 0.67 0.50 0.40 -0.38 0.14 0.07 0.03 -0.02 -0.50 -0.31

22 CYP3A4 205998_x_at -0.70 -0.54 -0.56 0.58 -0.46 -0.21 -0.29 -0.28 0.22 -0.06 CYP3A43 211440_x_at 0.400.06 0.02 -0.20 -0.09 -0.12-0.30 -0.46 -0.65 -0.73 CYP3A43 211441_x_at 0.600.18 0.33 -0.44 -0.07 -0.20-0.14 -0.48 -0.76 -0.66 CYP3A43 211442_x_at -0.31 -0.41 -0.82 0.56 -0.24 -0.04 -0.41 -0.52 0.24 -0.10 CYP3A7 211843_x_at 0.71 0.49 0.42 -0.65 0.19 0.03 0.09 0.02 -0.46 -0.43 CYP4F8 210576_at -0.28 -0.39 -0.64 0.25 -0.30 -0.21 -0.37 -0.35 0.30 -0.10 DCK 203302_at -0.67 -0.69 -0.65 0.40 -0.46 -0.24 -0.31 -0.46 0.08 -0.13 DGUOK 209549_s_at 0.64 0.70 0.83 -0.61 0.70 0.48 0.63 0.66 -0.19 0.19 DGUOK 203816_at 0.380.57 0.53 -0.36 0.81 0.69 0.70 0.55 -0.02 0.26 DHFR 202534_x_at -0.30 -0.50 -0.66 0.53 -0.29 -0.14 -0.59 -0.54 -0.01 -0.50 DHFR 202532_s_at -0.43 -0.55 -0.69 0.64 -0.55 -0.36 -0.69 -0.60 0.04 -0.39 ERCC1 203719_at 0.66 0.43 0.56 -0.60 0.33 0.16 0.26 -0.04 -0.63 -0.22 ERCC2 (XPD) 213468_at 0.60 0.47 0.37 -0.59 0.67 0.52 0.45 0.27 -0.15 0.06 FAS 204781_s_at 0.240.56 0.38 -0.31 0.40 0.360.63 0.66 0.30 0.71 FPGS 202945_at 0.65 0.49 0.25 -0.67 0.20 0.06 0.11 0.06 -0.50 -0.38 GLUD1 200947_s_at 0.67 0.59 0.48 -0.51 0.84 0.68 0.43 0.49 -0.15 0.07 GLUD1 200946_x_at 0.72 0.66 0.49 -0.52 0.83 0.67 0.46 0.51 -0.10 0.13 GLUD2 215794_x_at 0.66 0.60 0.45 -0.53 0.79 0.65 0.47 0.47 -0.11 0.14 GMPS 214431_at 0.75 0.51 0.62 -0.56 0.51 0.29 0.19 0.09 -0.57 -0.32 GPX1 200736_s_at 0.62 0.65 0.44 -0.41 0.50 0.28 0.41 0.33 -0.01 0.16 GPX2 202831_at -0.35 -0.59 -0.58 0.27 -0.77 -0.62 -0.60 -0.77 -0.16 -0.47 HK2 202934_at 0.67 0.68 0.63 -0.66 0.48 0.29 0.50 0.63 -0.10 0.15 HOXA9 209905_at 0.440.04 0.06 -0.26 -0.18 -0.24-0.32 -0.32 -0.52 -0.67 IGJ 212592_at 0.90 0.78 0.60 -0.64 0.33 0.13 0.27 0.15 -0.42 -0.17 IL10 207433_at -0.27 0.14 0.25 -0.05 0.02 0.100.54 0.49 0.37 0.76 IL7R 205798_at -0.63 -0.67 -0.47 0.81 -0.36 -0.22 -0.59 -0.26 0.28 -0.04 IMPREDH1 204169_at 0.68 0.54 0.72 -0.57 0.33 0.11 0.35 0.26 -0.34 -0.06 IMPREDH2 201892_s_at 0.73 0.52 0.40 -0.40 0.49 0.32 0.14 0.22 -0.31 -0.28 MCL1 214056_at -0.26 0.04 0.02 0.08 -0.14 -0.110.26 0.31 0.49 0.64 MCL1 200798_x_at -0.06 0.26 0.10 -0.08 0.03 0.050.44 0.35 0.40 0.70 MCL1 200797_s_at -0.12 0.23 0.11 -0.18 0.14 0.190.56 0.47 0.38 0.71 MCL1 200796_s_at -0.08 0.28 0.19 -0.11 0.25 0.270.59 0.56 0.46 0.80 MLL 212076_at -0.90 -0.86 -0.66 0.61 -0.72 -0.53 -0.52 -0.55 0.15 -0.13

23 MLL 216624_s_at -0.89 -0.85 -0.54 0.56 -0.56 -0.43 -0.40 -0.41 0.25 -0.11 MVP 202180_s_at -0.15 0.19 0.33 -0.25 0.07 0.100.57 0.44 0.20 0.67 MYC 202431_s_at 0.480.23 0.41 -0.74 0.32 0.14 0.17 0.10 -0.44 -0.30 MYCN 209757_s_at -0.08 0.04 -0.39 0.71 0.13 0.23 -0.14 0.14 0.58 0.23 NAIP 204860_s_at -0.33 -0.40 -0.64 0.71 -0.39 -0.19 -0.51 -0.51 0.13 -0.18 NAIP 204861_s_at -0.53 -0.50 -0.65 0.80 -0.39 -0.15 -0.46 -0.45 0.16 -0.12 NDUFA3 218563_at 0.64 0.39 0.56 -0.36 0.13 -0.06 -0.08 -0.16 -0.61 -0.37 NDUFA5 201304_at -0.25 -0.53 -0.17 -0.05 -0.49 -0.53-0.45 -0.74 -0.46 -0.52 NDUFA7 202785_at 0.400.22 0.64 -0.46 0.35 0.15 0.12 -0.02 -0.65 -0.38 NDUFA8 218160_at 0.70 0.51 0.72 -0.51 0.38 0.06 0.11 0.25 -0.33 -0.14 NDUFA9 208969_at 0.76 0.51 0.62 -0.43 0.45 0.19 0.14 0.18 -0.27 -0.12 NDUFAB1 202077_at 0.70 0.44 0.68 -0.49 0.35 0.15 0.18 0.17 -0.38 -0.12 NDUFAF1 204125_at 0.78 0.68 0.69 -0.58 0.38 0.17 0.29 0.41 -0.23 0.12 NDUFB1 206790_s_at -0.82 -0.85 -0.42 0.33 -0.75 -0.67 -0.48 -0.58 0.02 -0.11 NDUFB2 218200_s_at 0.68 0.42 0.56 -0.52 0.15 0.00 0.13 0.02 -0.47 -0.25 NDUFB2 218201_at 0.69 0.42 0.62 -0.57 0.18 0.03 0.18 0.01 -0.53 -0.22 NDUFB3 203371_s_at 0.510.34 0.68 -0.38 0.06 -0.08 0.07 0.09 -0.42 -0.09 NDUFB4 218226_s_at 0.620.48 0.68 -0.31 0.34 0.14 0.06 0.13 -0.45 -0.18 NDUFB5 203621_at 0.610.55 0.49 -0.66 0.60 0.35 0.33 0.37 -0.25 -0.02 NDUFC1 203478_at 0.520.31 0.73 -0.35 0.09 -0.06 0.08 0.02 -0.58 -0.28 NDUFS2 201966_at 0.620.54 0.59 -0.64 0.60 0.34 0.44 0.43 -0.11 0.08 NDUFS3 201740_at 0.70 0.40 0.42 -0.42 0.32 0.13 0.07 0.07 -0.27 -0.19 NDUFS4 209303_at 0.77 0.63 0.41 -0.47 0.54 0.36 0.29 0.39 -0.05 0.06 NDUFS5 201757_at 0.73 0.45 0.58 -0.52 0.22 0.03 0.17 0.02 -0.49 -0.26 NDUFS7 211752_s_at 0.77 0.58 0.66 -0.52 0.58 0.31 0.22 0.25 -0.35 -0.17 NDUFS8 203190_at 0.77 0.54 0.56 -0.38 0.40 0.20 0.13 0.24 -0.27 -0.08 NDUFS8 203189_s_at 0.65 0.43 0.36 -0.33 0.27 0.14 0.08 0.08 -0.23 -0.08 NF1 212676_at -0.75 -0.71 -0.48 0.55 -0.65 -0.44 -0.36 -0.58 -0.02 -0.20 NF1 211914_x_at -0.88 -0.80 -0.59 0.59 -0.57 -0.40 -0.43 -0.48 0.15 -0.19 NF1 212678_at -0.69 -0.62 -0.52 0.48 -0.42 -0.22 -0.25 -0.40 0.01 -0.13 NF1 204323_x_at -0.84 -0.68 -0.59 0.61 -0.47 -0.27 -0.30 -0.39 0.21 -0.06 NF1 211094_s_at -0.70 -0.55 -0.42 0.66 -0.36 -0.20 -0.31 -0.29 0.16 -0.03 NF1 211095_at -0.26 -0.21 -0.64 0.06 0.12 0.33 0.03 -0.07 0.16 0.01

24 NF1 210631_at -0.41 -0.28 -0.40 0.66 -0.30 -0.10 -0.25 -0.01 0.32 0.24 OAZIN 201772_at -0.28 -0.15 -0.39 0.71 -0.24 -0.10 -0.21 -0.28 0.40 0.27 Omi-HtrA2 211152_s_at 0.380.50 0.66 -0.25 0.65 0.55 0.46 0.61 -0.20 0.14 Omi-HtrA2 203089_s_at 0.40 0.64 0.67 -0.44 0.71 0.62 0.71 0.69 -0.09 0.41 P53AIP1 220402_at -0.39 -0.45 -0.55 0.22 -0.72 -0.70 -0.49 -0.47 0.18 -0.18 PARP1 208644_at 0.72 0.68 0.49 -0.62 0.63 0.48 0.59 0.42 -0.17 0.09 PDCD5 219275_at 0.72 0.59 0.69 -0.83 0.41 0.23 0.44 0.29 -0.42 0.01 PIK3C2B 204484_at -0.67 -0.65 -0.44 0.35 -0.48 -0.44 -0.40 -0.47 0.00 -0.25 PIK3C3 215394_at -0.61 -0.67 -0.48 0.45 -0.64 -0.56 -0.54 -0.59 0.02 -0.29 PIK3CD 203879_at 0.110.36 -0.09 -0.07 0.22 0.280.48 0.41 0.51 0.70 PRDX2 215067_x_at -0.84 -0.67 -0.65 0.77 -0.40 -0.19 -0.33 -0.20 0.47 0.09 PRDX4 201923_at 0.610.36 0.58 -0.65 0.43 0.24 0.19 0.24 -0.45 -0.14 PRDX6 200844_s_at 0.510.18 0.28 -0.31 0.09 0.01-0.02 -0.42 -0.66 -0.49 PRDX6 200845_s_at 0.03-0.23 -0.13 0.07 -0.34 -0.31-0.29 -0.73 -0.43 -0.45 RAD23A 201046_s_at 0.77 0.59 0.65 -0.53 0.61 0.45 0.31 0.28 -0.54 -0.19 RAD23A 201039_s_at 0.67 0.58 0.77 -0.47 0.31 0.19 0.32 0.31 -0.45 0.03 RARS 201330_at 0.80 0.68 0.52 -0.62 0.59 0.46 0.34 0.37 -0.37 0.00 RIPK2 209545_s_at 0.330.36 0.03 -0.26 0.64 0.51 0.25 0.53 0.32 0.15 RIPK5 211514_at -0.37 -0.33 -0.10 0.17 -0.73 -0.65 -0.32 -0.27 0.03 -0.03 RIPX 210251_s_at -0.46 -0.66 -0.46 0.39 -0.63 -0.50 -0.64 -0.72 -0.31 -0.62 RIPX 213939_s_at -0.43 -0.65 -0.57 0.39 -0.66 -0.52 -0.67 -0.74 -0.27 -0.62 RIPX 203724_s_at -0.40 -0.63 -0.46 0.24 -0.52 -0.42-0.55 -0.65 -0.33 -0.60 RIPX 213430_at -0.61 -0.74 -0.54 0.30 -0.59 -0.43 -0.52 -0.70 -0.28 -0.52 RRM2 209773_s_at 0.520.39 0.65 -0.51 0.28 0.13 0.14 0.19 -0.44 -0.09 SMAC 219350_s_at 0.75 0.57 0.52 -0.61 0.60 0.39 0.32 0.33 -0.26 -0.02 SOD1 200642_at 0.69 0.44 0.57 -0.60 0.34 0.20 0.29 0.12 -0.41 -0.09 SOD2 215223_s_at 0.72 0.68 0.45 -0.40 0.67 0.51 0.40 0.47 0.00 0.16 SOD2 216841_s_at 0.64 0.69 0.25 -0.11 0.50 0.44 0.37 0.41 0.19 0.30 TNFAIP8 208296_x_at -0.48 -0.38 -0.42 0.69 -0.23 -0.17 -0.37 -0.22 0.27 -0.13 TNFAIP8 210260_s_at -0.54 -0.43 -0.43 0.73 -0.27 -0.20 -0.33 -0.26 0.34 -0.08 TNFRSF11A 207037_at -0.24 0.14 0.34 -0.15 0.12 0.160.59 0.51 0.31 0.72 TNFRSF17 206641_at 0.21 0.28 0.45 -0.64 0.11 0.04 0.49 0.19 -0.35 -0.20 TNFRSF21 218856_at 0.02 -0.31 -0.06 0.22 -0.10 -0.21-0.55 -0.40 -0.32 -0.68

25 TNFRSF4 214228_x_at -0.13 0.25 0.38 -0.24 0.28 0.31 0.69 0.61 0.32 0.76 TNFRSF9 207536_s_at -0.21 0.16 0.43 -0.20 0.12 0.150.60 0.49 0.20 0.64 TNFSF11 211153_s_at 0.090.27 0.65 -0.44 0.13 0.08 0.50 0.42 -0.13 0.33 TNFSF12 205611_at -0.09 0.24 0.23 -0.21 0.20 0.210.51 0.58 0.37 0.64 TNFSF4 207426_s_at -0.45 -0.53 -0.28 0.49 -0.45 -0.38 -0.64 -0.44 -0.18 -0.43 TNIP1 207196_s_at 0.140.50 0.21 -0.33 0.42 0.41 0.65 0.65 0.34 0.69 TNIP2 218335_x_at 0.450.55 0.71 -0.68 0.32 0.14 0.58 0.54 -0.10 0.33 TNIP2 48531_at 0.440.61 0.56 -0.52 0.31 0.22 0.64 0.54 0.07 0.55 TOP2A 201292_at -0.24 -0.40 -0.68 0.41 -0.47 -0.30 -0.58 -0.53 0.04 -0.44 TPMT 203671_at -0.32 -0.16 0.23 -0.07 0.05 -0.050.08 0.18 -0.07 -0.03 TPMT 203672_at 0.380.47 0.39 -0.37 0.27 0.190.31 0.25 -0.16 0.30 TRADD 1729_at -0.20 0.22 0.19 0.00 0.28 0.300.58 0.72 0.63 0.88 TRAF3 208315_x_at 0.54 0.71 0.66 -0.45 0.79 0.72 0.85 0.69 0.00 0.47 TRIAP1 218403_at 0.87 0.78 0.53 -0.54 0.53 0.33 0.36 0.42 -0.08 0.07 UGT1A10 207126_x_at -0.29 -0.32 -0.36 0.30 -0.66 -0.60 -0.41 -0.37 0.13 -0.30 XO (XDH) 210301_at 0.55 0.37 0.13 -0.22 0.11 0.05 -0.09 -0.03 -0.31 -0.41

26 Table S3 –Details of Ingenuity Pathway Analysis for Individual Drugs, Drug Pairs, Genes of the 10 Drug Model, and the GC-MTX Reciprocity Index (data represent p-value and number of molecules (#) associated with significant sub-pathways).

Specific Sub- ARA GC- Master Pathway GCs # TPs # ACs # VCR # MTX # ASP # # Model # # Pathway C MTX Antioxidant Gluathione 1.01 4 pathways Metabolism E-02 Calcium Signalling Calcium Signalling 1.89E- 10 02 Cancer Cancer 1.48 114 1.63 172 1.56 175 1.02 45 4.29 42 1.02 33 1.75 28 9.06E- 101 E-03 E-04 E-07 E-02 E-03 E-02 E-03 04 Cancer Cell cycle, cancer, 9.08 13 death E-05 Cancer Molecular Mech. of 2.00 27 Cancer E-05 Cell Death Apoptosis signalling 1.78 9 E-03 Cell Death Cell Death 2.00 80 1.89 155 1.01 144 1.33 61 2.72 16 6.22E- 109 1.47 154 E-03 E-06 E-04 E-03 E-02 04 E-04 Cell Death Death Receptor 2.67 8 Signalling E-03 Cell Death TNFR1 Signalling 1.36 8 E-04 Cell Growth and Cell Cycle 1.30 12 4.29 23 7.82 7 1.62 82 Proliferation E-02 E-03 E-03 E-03 Cell Growth and Cell Growth and 2.33 159 3.69 62 1.75 21 1.07 31 Proliferation Proliferation E-07 E-05 E-03 E-03 Cellular function Cell to cell signalling 6.89 31 and Maintenance and interaction E-04 Cellular function Cellular Movement 5.03 11 3.71 36 and Maintenance E-05 E-03 Cellular function Phospholipid 2.49 7 and Maintenance degradation E-03 Differentiation/ Cell morphology 1.75 14 Development E-03 Differentiation/ Cellular Assembly & 1.98 31 7.87E- 58 6.50 61 Development Organization E-04 04 E-04 Differentiation/ Cellular Development 1.43 92 1.75 14 4.92 118 Development E-04 E-03 E-03

27 Differentiation/ Organismal 4.9268 Development Development E-03 Differentiation/ Skeletal and Muscular 1.47 38 Development System Development E-06 Differentiation/ Tissue Development 2.33 20 Development E-03 DNA Replication, DNA Replication, 1.48 10 2.20 34 4.29 7 8.70 3 1.07 31 Recombination, Recombination, E-04 E-04 E-03 E-04 E-03 Repair Repair DNA Replication, Nucleic Acid 3.81 9 7.15 11 Recombination, Metabolism E-03 E-04 Repair DNA Replication, Purine Metabolism 2.37 24 Recombination, E-03 Repair Drug Metabolism Cytochrome P450 8.104 Panel E-03 Drug Metabolism Drug metabolism 5.25 7 E-03 Drug Metabolism Xenobiotic 2.86 24 Metabolism E-05 Signalling Estrogen Receptor Estrogen Receptor 2.4515 Signalling Signalling E-04 Gene Expression 6.77 75 1.21 114 2.31 24 7.41 99 2.28E- 8 3.92 142 E-04 E-06 E-03 E-04 06 E-06 Gene Expression Transcription 1.25 21 E-07 Genetic Disorder Genetic Disorder 1.12 303 3.81 21 1.28 11 E-04 E-03 E-02 Haematological B-cell activating 2.08 7 System factor signalling E-04 Haematological B-cell development 3.20 6 System E-03 Haematological Haematological 6.10 43 8.52 21 4.29 19 2.66E- 30 System Disorder E-03 E-03 E-03 03 Haematological Haematological 1.43 33 1.70 28 2.66E- 19 System System Development E-04 E-03 03 and Function Hypoxia-inducible Hypoxia-inducible 1.23 11

28 Factor Signalling Factor Signalling E-04 Immune Responses IL-1 Signalling 6.50 12 E-05 Immune Responses IL-8 Signalling 2.82 16 E-04 Immune Responses Infectious Disease 1.87 38 3.33E- 52 9.37 95 E-04 03 E-07 Immune Responses Inflammatory 1.16 20 2.99 28 Responses E-03 E-04 Immune Responses Role of PKR in 7.96 7 interferon Induction E-04 and antiviral response Immune Responses Role of RIG1-like 2.51 7 4.69 5 Receptors in antiviral E-04 E-03 innate Immunity MAPK Signalling Erk5 Signalling 2.08E- 7 03 MAPK Signalling LPS-Stimulated 1.89 7 MAPK Signalling E-03 Metabolism Amino Acid 2.31 3 5.07E- 5 4.92 38 Metabolism E-03 04 E-03 Metabolism Carbohydrate 3.39 24 2.67 18 3.26 9 Metabolism E-03 E-03 E-03 Metabolism Energy Production 3.90 3 1.75 6 4.11 14 E-04 E-02 E-03 Metabolism Glycolysis/ 2.67 10 Gluconeogenesis E-03 Metabolism Lipid Metabolism 1.41 24 2.35 7 8.80 21 4.92 16 E-02 E-02 E-03 E-03 Metabolism Metabolic Disease 1.86 14 E-02 Metabolism Mitochondrial 7.04 15 Dysfunction E-03 Metabolism Oxidative 2.18 16 Phosphorylation E-03 Metabolism Polyamine Regulation 5.16 18 in colon cancer E-08 Metabolism PPARa/RXRa 1.65 16 9.01 12 3.02E- 9 Activation E-04 E-03 02 Molecular Molecular Transport 2.67 24 1.89 31 5.65 41

29 Transport E-03 E-04 E-04 Post-Translational Post-Translational 1.09 69 1.75 11 1.98E- 16 1.13 76 Modification Modification E-04 E-03 04 E-04 Post-Translational Protein 5.16 29 Modification Ubiquitination E-08 Protein Synthesis EIF2 Pathway 2.50 9 4.29 16 E-04 E-07 Protein Synthesis Protein Synthesis 2.17 60 E-07 Protein Synthesis Regulation of eIF4 & 3.4615 p70S6K Signalling E-05 Protein Synthesis Synthesis of Protein 5.20 43 E-04 RNA Trafficking RNA Trafficking 1.89 8 E-04 RNA-post RNA-post 3.37 8 7.43 33 transcriptional transcriptional E-04 E-05 modification modification Small Molecule Small Molecule 2.31 43 7.15 31 1.75 40 5.07E- 36 2.68 65 Biochem Biochem E-03 E-04 E-03 04 E-04

30 Table S4. Ten Drug Model Prediction Accuracies Across Different Cohorts

Cohort Platform N Acc PPV NPV Sens Spec P-value CCG-1961 HG-U133Plus2 50 78 76 79 73 82 <0.0005 POG-8704† HG-U133A 41 76 77 75 59 88 <0.005 POG-9404† HG-U133Plus2 44 75 67 77 43 90 <0.05

N, cohort size; Acc, Accuracy; PPV, Positive Predicted Value; NPV, Negative Predicted Value; Sens, Sensitivity; Spec, Specificity (all model performances given as %); P-value, Fisher’s Exact Test of model performance; † Microarray data downloaded from Winter et al (2007).

31 Table S5 – Logistic Regression Models Used to Predict Patient Outcome in Each T-ALL Cohort. Each drug variable in the equation represents its individual resistance score, equivalent to predicted IC50, calculated from patient microarray data using cell line drug-gene modelling.

Cohort Logistic Regression Model

CCG-1961 Relapse/non-relapse probability = -0.4389 + -0.2198*DNR + -0.8597*MPRED + -0.1183*VCR + -0.2704*ASP + -0.3694*ARAC + 0.1703*DEX + 0.7415*MTX +1.3888*6MP + 0.2030*6TG +-0.6082 *DOX

POG-8704 Relapse/non-relapse probability = -0.38758 + -1.76394*DNR + 0.62645*MPRED + 0.3848*VCR + -0.50941 *ASP + 1.67697 *ARAC + 0.70506*DEX +0.75118 *MTX + -1.22382 *6MP +-0.02327 *6TG +0.37029*DOX

POG-9404 Relapse/non-relapse probability = -1.13325 + 0.06879*DNR + 0.38953*MPRED + 0.75943*VCR + -1.06401*ASP + -1.86376 *ARAC + 0.44688 *DEX + 1.38195*MTX + -0.12170*6MP + -0.06479*6TG + -0.04820*DOX

32 Supplementary Figures

Figure S1 – Resistant Subgroups Within (A) POG-8704 and (B) POG-9404 Cohorts. Hierarchical clustering was performed using the drug contribution profiles of each individual specimen correctly predicted as relapse by the 10-drug model.

A B

Subgroup B Subgroup B Subgroup A Subgroup A

33