Supplementary Tables

Supplemental Table S1. COG treatment protocols pediatric ALL patients.

Treatment protocol Number of patients AALL0031 5 AALL01P2 1 AALL0232 7 AALL0331 2 AALL0433 1 AALL0434 15 AALL0622 1 AALL0631 3 AALL07P1 3 AALL0932 19 AALL1122 4 AALL01131 12 Supplementary Table S2. This table contains the “Rosetta Stone” for the antibody and protein nomenclature (HUGO, MiMI, GeneCards) together with the RPPA staining details, including the primary and secondary antibody dilutions, the R2 scores for antibody validation, catalog number and the antibody source. Functional Protein Name Rosetta Stone RPPA Staining Details Category Functional Effect Common Name RPPA Antibody Huge Name (added MiMI Antibody R2, WB vs. Antibody 2nd Ab Full Name/Description from GeneCards of Mfg Claimed Manufacturer Catalog# Functional Group Name with PTMs) Name Source RPPA Dilution dilution Phosphorylation Target

AKT1 AKT1 AKT1 v-akt murine thymoma viral oncogene homolog 1 AKT1 Cell Signaling 9272 Rabbit > 0.7 200 15000 PI3KAKT

AKT1/AKT2/AKT3 AKT1_2_3.pS473 AKT1 v-akt murine thymoma viral oncogene homolog 1 Activation AKT-P473(Ser) Cell Signaling 9271 Rabbit > 0.7 150 20000 PI3KAKT Phospho Ser473 AKT1/AKT2/AKT3 AKT1_2_3.pT308 AKT1 v-akt murine thymoma viral oncogene homolog 1 Activation AKT-P308(Thr) Cell Signaling 9275 Rabbit > 0.7 200 20000 PI3KAKT Phospho Thr308

ASNS ASNS ASNS asparagine synthetase (glutamine-hydrolyzing) ASNS Sigma HPA029318 Rabbit 0.5-0.7 800 20000 Metabolic

ATF3 ATF3 ATF3 activating transcription factor 3 ATF3 Abcam ab87213 Rabbit > 0.7 500 20000 Autophagy, CREB

BAD BAD BAD BCL2-associated agonist of cell death Bad Cell Signaling 9292 Rabbit > 0.7 100 20000 BH3

BAK1 BAK1 BAK1 BCL2-antagonist/killer 1 Bak Cell Signaling 3814 Rabbit 0.5-0.7 100 20000 BH3

BAX BAX BAX BCL2-associated X protein Bax Cell Signaling 2772 Rabbit > 0.7 200 20000 BH3

BCL2 BCL2 BCL2 B-cell CLL/lymphoma 2 Bcl2 DAKO M0887 Mouse > 0.7 300 20000 BH3

BCL2L1 BCL2L1 BCL2L1 BCL2-like 1 Bcl-XL Cell Signaling 2762 Rabbit > 0.7 200 20000 BH3

BCL2L11 BCL2L11 BCL2L11 BCL2-like 11 (apoptosis facilitator) Bim Epitomics 1036-1 Rabbit > 0.7 200 20000 BH3

BECN1 BECN1 BECN1 beclin 1, autophagy related Beclin-1 Cell Signaling 3738 Rabbit > 0.7 500 20000 Autophagy, CREB

BID BID BID BH3 interacting domain death agonist Bid Cell Signaling 2002 Rabbit 0.5-0.7 300 20000 BH3

BIRC2 BIRC2 BIRC2 baculoviral IAP repeat containing 2 CIAP-1 Upstate 07-759 Rabbit 0.5-0.7 500 20000 IAP

XIAP XIAP BIRC4 X-linked inhibitor of apoptosis XIAP Cell Signaling 2042 Rabbit > 0.7 400 20000 IAP

BIRC5 BIRC5 BIRC5 baculoviral IAP repeat containing 5 Survivin Cell Signaling 2802 Rabbit ? 100 20000 IAP

BMI1 BMI1 BMI1 BMI1 polycomb ring finger oncogene Bmi-1 Cell Signaling 2830 Rabbit 0.5-0.7 200 20000 Histone

BRAF BRAF BRAF v-raf murine sarcoma viral oncogene homolog B Raf-B Santa Cruz sc5284 Mouse 0.5-0.7 200 20000 MEK

BRCA2 BRCA2 BRCA2 BRCA2, DNA Repair Associated BRCA2 CellSignaling 9012 Rabbit 0.5-0.7 100 20000 HIPPO

CASP3 CASP3 CASP3 caspase 3, apoptosis-related cysteine peptidase caspase 3 Cell Signaling 9662 Rabbit 0.5-0.7 1000 20000 ApopOccur

Caspase 3 cleaved CASP3.cl175 CASP3 Cleaved CASP3 caspase 3, apoptosis-related cysteine peptidase Cell Signaling 9664 Rabbit 0.5-0.7 100 20000 ApopOccur Asp175 Caspase 7 cleaved CASP7.cl198 CASP7 Cleaved Asp198 CASP7 caspase 7, apoptosis-related cysteine peptidase Cell Signaling 9491 Rabbit 0.5-0.7 300 20000 ApopOccur Asp198

CASP8 CASP8 CASP8 caspase 8, apoptosis-related cysteine peptidase Caspase 8 Cell Signaling 9746 Mouse ? 1000 20000 ApopOccur

CASP9 CASP9 CASP9 caspase 9, apoptosis-related cysteine peptidase Caspase 9 BD Pharmingen 551246 Mouse 0.5-0.7 150 20000 ApopOccur

Caspase 9 cleaved CASP9.cl315 CASP9 Cleaved Asp315 CASP9 caspase 9, apoptosis-related cysteine peptidase Cell Signaling 9505 Rabbit ? 200 20000 ApopOccur Asp315 Caspase 9 cleaved CASP9.cl330 CASP9 Cleaved Asp330 CASP9 caspase 9, apoptosis-related cysteine peptidase Cell Signaling 9501 Rabbit ? 200 20000 ApopOccur Asp330

CAV1 CAV1 CAV1 caveolin 1, caveolae protein, 22kDa Caveolin-1 Cell Signaling 3238 Rabbit > 0.7 150 20000 Adhesion

CBL CBL CBL Cbl proto-oncogene, E3 ubiquitin protein ligase Cbl-c BD Transduction Lab 610441 Mouse 0.5-0.7 1000 20000 Ubiquitin

CCNB1 CCNB1 CCNB1 cyclin B1 Cyclin B1 Santa Cruz SC245 Mouse > 0.7 150 20000 CellCycle

CCND1 CCND1 CCND1 cyclin D1 Cyclin D1(M-20) Santa Cruz sc718 Rabbit > 0.7 400 20000 CellCycle

CCND3 CCND3 CCND3 cyclin D3 Cyclin D3 Cell Signaling 2936 Mouse > 0.7 150 20000 CellCycle

CCNE1 CCNE1 CCNE1 cyclin E1 Cyclin E Santa Cruz sc-247 Mouse > 0.7 200 20000 CellCycle

CCNE2 CCNE2 CCNE2 cyclin E2 Cyclin E2 Epitomics 1142-1 Rabbit ? 300 20000 CellCycle

CD74 molecule, major histocompatibility complex, CD74 CD74 CD74 CD74 Santa Cruz sc-6262 Mouse 0.5-0.7 150 20000 T-cell class II invariant chain

CDK1 CDK1 CDC2 cyclin-dependent kinase 1 CDC2 Calbiochem cc01 Mouse 0.5-0.7 200 20000 CellCycle

CDK2 CDK2 CDK2 cyclin-dependent kinase 2 CDK2 Santa Cruz SC6248 Mouse > 0.7 200 20000 CellCycle

CDK4 CDK4 CDK4 cyclin-dependent kinase 4 CDK4 Cell Signaling 2906 Mouse > 0.7 200 20000 CellCycle

CDKN1A CDKN1A CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) P21/Waf Cell Signaling 2946 Mouse ? 400 20000 CellCycle

CDKN1B CDKN1B CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) P27 Santa Cruz sc-528 Rabbit > 0.7 250 20000 CellCycle

CDKN1B.pS10 CDKN1B Phospho Ser10 CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) Apoptosis altered P27ps10 Epitomics 2187-1 Rabbit > 0.7 500 20000 CellCycle

CDKN2A CDKN2A CDKN2A cyclin-dependent kinase inhibitor 2A P16 Santa Cruz sc468 Rabbit > 0.7 10000 20000 CellCycle

caseinolytic mitochondrial matrix peptidase CLPP CLPP CLPP CLPP Abcam ab124822 Rabbit > 0.7 1000 20000 Histone proteolytic subunit

CREB1 CREB1 CREB1 cAMP responsive element binding protein 1 CREB Epitomics 1496-1 Rabbit > 0.7 2000 20000 CREB

CREB1.pS133 CREB2 Phospho Ser133 CREB1 cAMP responsive element binding protein 1 Activation CREB-p(ser133) Epitomics 1113-1 Rabbit 0.5-0.7 2000 20000 CREB

catenin (cadherin-associated protein), alpha 1, CTNNA1 CTNNA1 CTNNA1 Catenin-alpha Thermo CA1030 Mouse ? 300 20000 WNT 102kDa catenin (cadherin-associated protein), beta 1, CTNNB1 CTNNB1 CTNNB1 Catenin-beta Cell Signaling 9562 Rabbit > 0.7 150 20000 WNT 88kDa Histone, RPS6, DDX17 DDX17 DDX17 DEAD-Box Helicase 17 DDX17 Abcam ab180190 Rabbit 0.5-0.7 2000 20000 Transcription

DIABLO DIABLO DIABLO blo, IAP-binding mitochondrial protein Smac/Diablo Cell Signaling 2954 Mouse ? 5000 20000 IAP

H00001745- DLX1 DLX1 DLX1 distal-less homeobox 1 DLX1 Abnova Mouse 0.5-0.7 1500 20000 Transcription M01

DUSP6 DUSP6 DUSP6 dual specificity phosphatase 6 DUSP6 Abcam ab76310 Rabbit > 0.7 5000 20000 MEK

EGFR EGFR EGFR Epiidermal growth factor receptor EGFR Santa Cruz sc-03 Rabbit > 0.7 500 20000 mTOR, STP

H00005610- EIF2AK2 EIF2AK2 EIF2AK2 ryotic translation initiation factor 2-alpha kinase 2 PRKR(EIF2AK2) Abnova Mouse 0.5-0.7 10000 20000 Transcription M02 EIF2AK2 Phospho EIF2AK2.pT451 EIF2AK2 ryotic translation initiation factor 2-alpha kinase 2 Activation PRKRpTh451(EIF2AK2) Invitrogen 44-668G Rabbit ? 3000 20000 Transcription Thr451 eukaryotic translation initiation factor 2, subunit 1 EIF2S1 EIF2S1 EIF2S1 elF2 Cell Signaling 9722 Rabbit 0.5-0.7 4000 20000 Transcription alpha, 35kDa eukaryotic translation initiation factor 2, subunit 1 EIF2S1.pS51. EIF2S1 Phospho Ser51 EIF2S1 Stabalizes phospho-eIF2-alpha Cell Signaling 9721 Rabbit > 0.7 200 20000 Transcription alpha, 35kDa

EIF4E EIF4E EIF4E otic translation initiation factor 4E eIF4E Cell Signaling 9742 Rabbit > 0.7 800 20000 Transcription

ELK1.pS383 ELK1 Phospho Ser383 ELK1 ELK1, member of ETS oncogene family Activation ElK(phospho-ser383) Cell Signaling 9181 Rabbit 0.5-0.7 150 20000 MEK, PI3KAKT

v-erb-b2 avian erythroblastic leukemia viral ERBB2 ERBB2 ERBB2 HER2/Erb2 Cell Signaling 2242 Rabbit > 0.7 300 20000 STP oncogene homolog 2 v-erb-b2 avian erythroblastic leukemia viral ERBB2.pY1248 ERBB2 Phospho Tyr1248 ERBB2 Activation HER2(p-Tyr1248) Upstate 06-229 Rabbit 0.5-0.7 2000 20000 STP oncogene homolog 2

IRE1 ERN1 ERN1 Endoplasmic reticulum to nucleus signaling 1 IRE1 Cell Signaling 3294 Rabbit 0.5-0.7 1000 20000 Ubiquitin

FLI1 Fli1 FLI1 Fli-1 proto-oncogene, ETS transcription factor Fli Dennis Watson Rabbit > 0.7 4000 20000 FLI1, Histone

FN1 FN1 FN1 fibronectin 1 Fibronectin Epitomics 1574 Rabbit > 0.7 20000 20000 Adhesion

FKHRL1/FoxO3a (P- FOXO3-phospho FOXO3 forkhead box O3 Inactivation FoxO3a Cell Signaling 9465 Rabbit 0.5-0.7 20000 20000 CellCycle, PI3KAKT Ser 318/321) Ser318/321

FOXO3A FOXO3 FOXO3 forkhead box O3 FoxO3a Cell Signaling 9467 Rabbit 0.5-0.7 500 20000 CellCycle, PI3KAKT

mechanistic target of rapamycin (serine/threonine MTOR.pS2448 MTOR-phospho Ser2448 FRAP1 Activation mTor(p-Ser2448) Cell Signaling 2971 Rabbit 0.5-0.7 200 20000 mTOR kinase) mechanistic target of rapamycin (serine/threonine MTOR MTOR FRAP1 mTor Cell Signaling 2983 Rabbit > 0.7 300 20000 mTOR kinase)

GAB2 GAB2 GAB2 GRB2-associated binding protein 2 Gab2 Cell Signaling 3239 Rabbit > 0.7 800 20000 PI3KAKT Tyr452 is a potential GAB2.pY452 GAB2 Phospho Tyr452 GAB2 GRB2-associated binding protein 2 binding site of p85, Gab2-pTyr452 Cell Signaling 3882 Rabbit 0.5-0.7 75 20000 PI3KAKT the regulatory GATA binding protein 1 (globin transcription Differentiation, GATA1 GATA1 GATA1 GATA-1 Cell Signaling 3535 Rabbit > 0.7 2000 20000 factor 1) Transcription Differentiation, GATA3 GATA3 GATA3 GATA binding protein 3 GATA-3 BD Bioscience 558686 Mouse > 0.7 800 20000 Transcription

GRP78 GRP78 GRP78 Heat shock protein family A (Hsp70) member 5 GRP78 BD Transduction Lab 610978 Mouse > 0.7 1000 20000 Heatshock, Ubiquitin

HDAC1 HDAC1 HDAC1 histone deacetylase 1 HDAC1 Imgenex IM-337 Rabbit 0.5-0.7 1000 20000 Histone

HDAC2 HDAC2 HDAC2 histone deacetylase 2 HDAC2 Santa Cruz sc-7899 Rabbit > 0.7 2000 20000 Histone

HDAC3 HDAC3 HDAC3 histone deacetylase 3 HDAC3 Cell Signaling 2632 Rabbit 0.5-0.7 150 20000 Histone

HDAC6 HDAC6 HDAC6 histone deacetylase 6 HDAC6 Cell Signaling 7558 Rabbit > 0.7 20000 20000 Histone

hypoxia inducible factor 1, alpha subunit (basic HIF1A HIF1A HIF1A HIF-1α BD Pharmingen 610959 Mouse 0.5-0.7 75 20000 Hypoxia helix-loop-helix transcription factor)

H3histone HIST3H3 HIST3H3 histone cluster 3, H3 H3histone Active Motif 39163 Rabbit > 0.7 30000 20000 Histone

H3K27Me3 HIST3H3-K27-Me3 HIST3H3 histone cluster 3, H3 , Lysine 27 methylation 3 Repression H3K27Me3 Active Motif 61017 Mouse > 0.7 4000 20000 Histone

H3K4Me2 HIST3H3-K4-Me2 HIST3H3 histone cluster 3, H3 , Lysine 4 methylation 2 Repression H3K4Me2 Active Motif 39141 Rabbit > 0.7 8000 20000 Histone

H3K4Me3 HIST3H3-K4-Me3 HIST3H3 histone cluster 3, H3 , Lysine 4 methylation 3 Repression H3K4Me3 Active Motif 39159 Rabbit 0.5-0.7 10000 20000 Histone HNRNPK HNRNPK HNRPK rogeneous nuclear ribonucleoprotein K hnRNPK Santa Cruz sc-28380 Mouse 0.5-0.7 10000 20000 Histone

HSPB1 HSPB1 HSPB1 heat shock 27kDa protein 1 HSP27 Cell Signaling 2402 Mouse 0.5-0.7 400 20000 Heatshock

IGF1R IGF1R IGF1R insulin-like growth factor 1 receptor IGF-1 receptor beta Cell Signaling 3027 Rabbit 0.5-0.7 1500 20000 STP

IGFBP2 IGFBP2 IGFBP2 insulin-like growth factor binding protein 2, 36kDa IGFBP-2 Cell Signaling 3922 Rabbit > 0.7 150 20000 Adhesion

INPP5D INPP5D INPP5D inositol polyphosphate-5-phosphatase, 145kDa SHIP1 Santa Cruz SC-8425 Mouse 0.5-0.7 50 20000 mTOR

INPPL1 INPPL1 INPPL1 inositol polyphosphate phosphatase-like 1 SHIP2 Cell Signaling 2730 Rabbit > 0.7 200 20000 mTOR

IRS1.pS1101 IRS1 Phospho Ser1101 IRS1 insulin receptor substrate 1 Inhibition IRS-1-p(ser1101) Cell Signaling 2385 Rabbit > 0.7 300 20000 mTOR, TP53

integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 ITGA2 ITGA2 ITGA2 CD49b BD Transduction Lab 611016 Mouse > 0.7 500 20000 Adhesion receptor) integrin, alpha L (antigen CD11A (p180), ITGAL ITGAL ITGAL lymphocyte function-associated antigen 1; alpha CD11a BD Transduction Lab 610826 Mouse > 0.7 500 20000 Adhesion polypeptide) integrin, beta 3 (platelet glycoprotein IIIa, antigen ITGB3 ITGB3 ITGB3 Integrin-beta3 Cell Signaling 4702 Rabbit ? 300 20000 Adhesion CD61)

JUN.pS73 JUN Phospho Ser73 JUN jun proto-oncogene Activation Jun-C-phospho ser73 Cell Signaling 9164 Rabbit > 0.7 150 20000 Transcription

JUNB JUNB JUNB jun B proto-oncogene Jun-B Cell Signaling 3755 Rabbit > 0.7 150 20000 Transcription

KDM1A KDM1A KDM1A lysine (K)-specific demethylase 1A LSD1 Cell Signaling 2184 Rabbit > 0.7 4000 20000 Histone

kinase insert domain receptor (a type III receptor KDR KDR KDR VEGFR2 Cell Signaling 2479 Rabbit > 0.7 1000 20000 Hypoxia tyrosine kinase) v-kit Hardy-Zuckerman 4 feline sarcoma viral KIT KIT KIT Kit-C Epitomics 1522 Rabbit > 0.7 1500 20000 MEK, STP oncogene homolog

LCK LCK LCK lymphocyte-specific protein tyrosine kinase Lck Cell Signaling 2752 Rabbit > 0.7 800 20000 T-cell

LEF1 LEF1 LEF1 lymphoid enhancer-binding factor 1 LEF1 Cell Signaling 2230 Rabbit > 0.7 1500 20000 WNT

LGALS3 LGALS3 LGALS3 lectin, galactoside-binding, soluble, 3 Galectin-3 Santa Cruz sc-32790 Mouse ? 400 20000 T-cell

v-yes-1 Yamaguchi sarcoma viral related LYN LYN LYN Lyn Cell Signaling 2732 Rabbit > 0.7 300 20000 MEK, STP oncogene homolog

MAP2K1 MAP2K1 MAP2K1 mitogen-activated protein kinase kinase 1 MEK Cell Signaling 9122 Rabbit > 0.7 8000 20000 MAPK

MAPK1 MAPK1 MAPK1 mitogen-activated protein kinase 1 Erk2 Santa Cruz Sc-154 Rabbit > 0.7 2000 20000 MAPK

MAPK14 MAPK14 MAPK14 mitogen-activated protein kinase 14 P38 Cell Signaling 9212 Rabbit > 0.7 1000 20000 MAPK

MAPK14.pT180Y182 MAPK14-p180p182 MAPK14 mitogen-activated protein kinase 14 Activation P38p180p182 Cell Signaling 9211 Rabbit > 0.7 200 20000 MAPK

MAPK9 MAPK9 MAPK9 mitogen-activated protein kinase 9 JNK2 Cell Signaling 4672 Rabbit 0.5-0.7 75 20000 MAPK, STAT

MCL1 MCL1 MCL1 myeloid cell leukemia sequence 1 (BCL2-related) MCL1 BD Pharmingen 559027 Mouse > 0.7 100 20000 BH3

MDM2 MDM2 MDM2 MDM2 oncogene, E3 ubiquitin protein ligase MDM2 Santa Cruz sc813 Rabbit 0.5-0.7 8000 20000 TP53

MDM4 MDM4 MDM4 Mdm4 p53 binding protein homolog (mouse) MDM4 Bethly lab A300-287A Rabbit > 0.7 8000 20000 TP53

MET.pY1230_1234_1 MET-phospho C-Met-pTyr MET met proto-oncogene Activation Biosource 44-888G Rabbit > 0.7 500 20000 STP 235 Py1230/1234/1235 1230/1234/1235 MSI2 MSI2 MSI2 Musashi RNA binding protein 2 MSI2 Chemicon MAB10085 Mouse 0.5-0.7 800 20000 RPS6

v-myc avian myelocytomatosis viral oncogene MYC MYC MYC Myc Cell Signaling 9402 Rabbit > 0.7 500 20000 CellCycle, Transcription homolog

NCL NCL NCL nucleolin C23 (nucleolin) Santa Cruz sc8031 Mouse > 0.7 400 20000 FLI1, Histone

NF2 NF2 NF2 neurofibromin 2 (merlin) NF2 Santa Cruz sc332 Rabbit 0.5-0.7 800 20000 Cytoskeletal, HIPPO

NF2.pS518 NF2-phospho ser518 NF2 neurofibromin 2 (merlin) Inactivation pNF2(ser518) Chemicon AB5607 Rabbit ? 800 20000 Cytoskeletal, HIPPO

v-rel avian reticuloendotheliosis viral oncogene RELA RELA NFKB1 NF-kB p65 Cell Signaling 3034 Rabbit 0.5-0.7 800 20000 PKC homolog A NOTCH1 cleaved Notch1-cleaved NOTCH1.cl1744 NOTCH1 notch 1 Activation Cell Signaling 4147 Rabbit > 0.7 600 20000 T-cell val1744 (Val1744)

NOTCH3 NOTCH3 NOTCH3 notch 3 Notch3 Santa Cruz sc5593 Rabbit 0.5-0.7 800 20000 T-cell

nucleophosmin (nucleolar phosphoprotein B23, NPM1.3542 NPM1mut AA3542 NPM1 NPM1.3542 Cell Signaling 3542 Rabbit 0.5-0.7 1000 20000 FLI1 numatrin)

NR4A1 NR4A1 NR4A1 nuclear receptor subfamily 4, group A, member 1 Nur77 Imgenex IMG-528 Rabbit ? 1000 20000 Transcription

NRP1 NRP1 NRP1 neuropilin 1 NRP1(neuropilin) Santa Cruz SC-5307 Mouse ? 75 20000 Cytoskeletal

ODC1 ODC1 ODC1 ornithine decarboxylase 1 ODC Shantz/Lisa Lab ? 800 20000 Metabolic

Private- PARK7 PARK7 PARK7 parkinson protein 7 DJ-1 Dr. Tek Mak Rabbit > 0.7 3000 20000 Autophagy Andreeff

PARP1 PARP1 PARP1 poly (ADP-ribose) polymerase 1 PARP Cell Signaling 9542 Rabbit 0.5-0.7 300 20000 ApopOccur

PARP1.cl214 PARP1-cleaved Asp 214 PARP1 poly (ADP-ribose) polymerase 1 Activation PARP(cleaved Asp214) Cell Signaling 9541 Rabbit > 0.7 150 20000 ApopOccur

PDK1 PDK1 PDK1 pyruvate dehydrogenase kinase, isozyme 1 PDK1 Cell Signaling 3062 Rabbit > 0.7 300 20000 mTOR

PDK1.pS241 PDK1-phospho ser241 PDK1 pyruvate dehydrogenase kinase, isozyme 1 Activation PDK1-p241(Ser) Cell Signaling 3061 Rabbit > 0.7 800 20000 mTOR

phosphotidylinositol-4,5-bisphosphate 3-kinase, PIK3CA PIK3CA PIK3CA PI3 K p110-alpha Epitomics 1683-1 Rabbit 0.5-0.7 400 20000 mTOR catalytic subunit alpha phosphoinositide-3-kinase, regulatory subunit 1 PIK3R1_2 PIK3R1/PIK3R2 PIK3R1 PI3 K p85 Cell Signaling 4292 Rabbit ? 150 20000 mTOR (alpha)

PIM1 PIM1 PIM1 pim-1 oncogene PIM1 Santa Cruz sc-13153 Mouse 0.5-0.7 150 20000 Differentiation

PIM2 PIM2 PIM2 pim-2 oncogene PIM2 Cell Signaling 4730 Rabbit > 0.7 300 20000 Differentiation

peroxisome proliferator-activated receptor PPARG PPARG PPARG PPARγ Santa Cruz sc7273 Mouse > 0.7 150 20000 Differentiation gamma

PRKCA PRKCA PRKCA protein kinase C, alpha PKCα Upstate 05-154 Mouse > 0.7 10000 20000 PKC

PRKCA.pS657 PRKCA-phospho ser657 PRKCA protein kinase C, alpha Activation PKCα-p657(Ser) Upstate 06-822 Rabbit 0.5-0.7 10000 20000 PKC

PRKCB.I PRKCB PRKCB protein kinase C, beta PKCβ I Santa Cruz sc8049 Mouse 0.5-0.7 500 20000 PKC

PRKCD.pS645 PRKCD-phospho Ser645 PRKCD protein kinase C, delta PKCδ-645(Ser) Upstate 07-874 Rabbit > 0.7 400 20000 PKC

PTEN PTEN PTEN phosphatase and tensin homolog PTEN Cell Signaling 9552 Rabbit > 0.7 4000 20000 mTOR

PTK2 PTK2 PTK2 protein tyrosine kinase 2 Fak Cell Signaling 3285 Rabbit > 0.7 1000 20000 Adhesion protein tyrosine phosphatase, non-receptor type PTPN11 PTPN11 PTPN11 SHP-2 Epitomics 1590-1 Rabbit 0.5-0.7 800 20000 STP 11

RB1 RB1 RB1 retinoblastoma 1 Rb BD Pharmingen 554136 Mouse > 0.7 1000 20000 CellCycle

RB1-phospho RB1.pS807_811 RB1 retinoblastoma 1 Inactivation Rb (P-Ser807/811) Cell Signaling 9308 Rabbit > 0.7 1000 20000 CellCycle ser807/811 RPTOR independent companion of mTOR complex RICTOR RICTOR RICTOR Rictor Cell Signaling 2114 Rabbit 0.5-0.7 200 20000 mTOR, RPS6 2 RICTOR Phospho RPTOR independent companion of mTOR complex Stimulates binding RICTOR.pT1135 RICTOR Rictor-P1135(Tyr) Cell Signaling 3806 Rabbit > 0.7 2000 20000 mTOR, RPS6 Thr1135 2 with 14-3-3

RPS6 RPS6 RPS6 ribosomal protein S6 S6 Ribosomal protein Cell Signaling 2217 Rabbit > 0.7 2000 20000 RPS6

S6 Ribosomal RPS6-phospho RPS6.pS235_236 RPS6 ribosomal protein S6 Activation protein(phospho- Cell Signaling 2211 Rabbit > 0.7 2000 20000 RPS6 ser235/236 ser235/236) S6 Ribosomal RPS6-phospho RPS6.pS240_244 RPS6 ribosomal protein S6 Activation protein(phospho- Cell Signaling 2215 Rabbit > 0.7 1000 20000 RPS6 ser240/244 ser240/244)

RPS6KB1 RPS6KB1 RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1 p70S6K Cell Signaling 9202 Rabbit > 0.7 250 20000 RPS6

RPS6KB1-phospho RPS6KB1.pT389 RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1 Activation p70S6K(p-thr389) Cell Signaling 9205 Rabbit > 0.7 250 20000 RPS6 thr389

RAPTOR RPTOR RPTOR Regulatory associated protein of mTOR complex 1 Raptor Cell Signaling 2280 Rabbit > 0.7 1000 20000 mTOR, RPS6

SFN SFN SFN stratifin X14.3.3Sigma Upstate 05-632 Mouse 500 20000 TP53

SIRT1 SIRT1 SIRT1 sirtuin 1 SIRT1 Abcam ab32441 Rabbit 0.5-0.7 2000 20000 Histone

SMAD1 SMAD1 SMAD1 SMAD family member 1 smad1 Epitomics 1649-1 Rabbit > 0.7 200 20000 SMAD

SMAD2 SMAD2 SMAD2 SMAD family member 2 SMAD2 Cell Signaling 5339 Rabbit > 0.7 10000 20000 SMAD

Smad2-p SMAD2.pS245 SMAD2.p245 SMAD2 SMAD family member 2 Activation Cell Signaling 3104 Rabbit > 0.7 800 20000 SMAD S245/250/255

SMAD2.pS465 SMAD2.pS465 SMAD2 SMAD family member 2 Activation Smad2-p S465/467 Cell Signaling 3108 Rabbit 0.5-0.7 800 20000 SMAD

SMAD3 SMAD3 SMAD3 SMAD family member 3 SMAD3 Cell Signaling 9523 Rabbit > 0.7 800 20000 SMAD

SMAD4 SMAD4 SMAD4 SMAD family member 4 smad4 Santa Cruz sc7966 Mouse > 0.7 400 20000 SMAD

SMAD5 SMAD5 SMAD5 SMAD family member 5 SMAD5 Epitomics 1682-1 Rabbit 0.5-0.7 2000 20000 SMAD

SMAD5.pS463 SMAD5pS463 SMAD5 SMAD family member 5 Activation Smad5-p S463/465 Epitomics 2224-1 Rabbit > 0.7 1000 20000 SMAD

SMAD6 SMAD6 SMAD6 SMAD family member 6 Smad6 Cell Signaling 9519 Rabbit ? 100 20000 SMAD

SOCS2 SOCS2 SOCS2 suppressor of cytokine signaling 2 SOCS2 Abcam ab92847 Rabbit > 0.7 400 20000 STP

spleen focus forming virus (SFFV) proviral SPI1 SPI1 SPI1 PU.1 Cell Signaling 2258 Rabbit 0.5-0.7 5000 20000 Transcription integration oncogene

SPP1 SPP1 SPP1 secreted phosphoprotein 1 Osteopotin Santa Cruz sc-21742 Mouse 0.5-0.7 200 20000 Adhesion

SQSTM1 SQSTM1 SQSTM1 sequestosome 1 P62 Santa Cruz sc-28359 Mouse 0.5-0.7 200 20000 Autophagy

v-src avian sarcoma (Schmidt-Ruppin A-2) viral SRC SRC SRC Src Upstate 05-184 Mouse > 0.7 2000 20000 SRC oncogene homolog v-src avian sarcoma (Schmidt-Ruppin A-2) viral SRC.pY416 SRC-phospho tyr416 SRC Activation Src(phospho-tyr416) Cell Signaling 2101 Rabbit > 0.7 200 20000 SRC oncogene homolog

SSBP2 SSBP2 SSBP2 single-stranded DNA binding protein 2 SSBP2-I(alpha) Private-Nagarajan Rabbit 0.5-0.7 2000 15000 Differentiation

signal transducer and activator of transcription 1, STAT1 STAT1 STAT1 stat1 Cell Signaling 9172 Rabbit > 0.7 400 20000 STAT 91kDa signal transducer and activator of transcription 1, Stat1(phospho- STAT1.pY701 STAT1-phospho tyr701 STAT1 Activation Cell Signaling 9171 Rabbit ? 200 20000 STAT 91kDa tyr701) signal transducer and activator of transcription 3 STAT3 STAT3 STAT3 Stat3 Upstate 06-596 Rabbit 0.5-0.7 200 20000 STAT (acute-phase response factor) signal transducer and activator of transcription 3 STAT3.pS727 STAT3-phospho ser727 STAT3 Activation Stat3-p727(Ser) Cell Signaling 9134 Rabbit 0.5-0.7 400 20000 STAT (acute-phase response factor) signal transducer and activator of transcription 3 STAT3.pY705 STAT3-phospho tyr705 STAT3 Activation Stat3 p705(Tyr) Cell Signaling 9131 Rabbit > 0.7 400 20000 STAT (acute-phase response factor)

STAT5A_B STAT5A/STAT5B STAT5A signal transducer and activator of transcription 5A Stat5 Cell Signaling 9352 Rabbit > 0.7 400 20000 STAT

STAT5A/STAT5B Stat5(phospho- STAT5A_B.pY694 STAT5A signal transducer and activator of transcription 5A Activation Cell Signaling 9351 Rabbit ? 100 20000 STAT phospho Tyr694 Tyr694) signal transducer and activator of transcription 6, Stat6(phospho- STAT6.pY641 STAT6-phospho tyr641 STAT6 Activation Cell Signaling 9361 Rabbit ? 500 20000 STAT interleukin-4 induced tyr641)

STK11 STK11 STK11 serine/threonine kinase 11 LKB1/STK11 Cell Signaling 3050 Rabbit 0.5-0.7 800 20000 Autophagy

STMN1 STMN1 STMN1 stathmin 1 Stathmin Epitomics 1972-1 Rabbit > 0.7 10000 20000 FLI1

TAZ TAZ TAZ Tafazzin Taz Abcam ab3961 Rabbit > 0.7 2000 20000 HIPPO

TAZ.pS89 TAZ Phospho Ser89 TAZ Tafazzin Inactivation Taz-P89(Ser) Santa Cruz sc-17610-R Rabbit ? 300 20000 HIPPO

TCF4 TCF4 TCF4 transcription factor 4 TCF-4 Santa Cruz sc8632 Goat ? 800 20000 Transcription

TGM2 TGM2 TGM2 transglutaminase 2 TG2 Abcam ab2386 Mouse > 0.7 4000 20000 Adhesion

TNK1 TNK1 TNK1 tyrosine kinase, non-receptor, 1 TNK1 Agent AP7722a Rabbit > 0.7 800 20000 MEK

TP53 TP53 TP53 tumor protein p53 TP53 BD Bioscience 554294 Mouse 0.5-0.7 750 20000 ApopReg, TP53

Blocks MDM2 TP53.pS15 TP53-pS15 TP53 tumor protein p53 TP53(phospho Ser 15) Cell Signaling 9284 Rabbit > 0.7 250 20000 ApopReg, TP53 binding NB100- TRIM24 TRIM24 TRIM24 tripartite motif containing 24 TRIM24 Novus Rabbit ? 2000 20000 Histone, TP53, Ubiquitin 2597

TSC2 TSC2 TSC2 tuberous sclerosis 2 TSC2 Epitomic 1613-1 Rabbit > 0.7 800 20000 Autophagy, mTOR

TSC2.pT1462 TSC2 TSC2 tuberous sclerosis 2 Inactivation TSC2 Cell Signaling 3617 Rabbit > 0.7 500 20000 Autophagy, mTOR

VASP VASP VASP vasodilator-stimulated phosphoprotein VASP Cell Signaling 3112 Rabbit ? 300 20000 Hypoxia

von Hippel-Lindau tumor suppressor, E3 ubiquitin VHL VHL VHL VHL Novus NB100-485 Rabbit 0.5-0.7 4000 20000 Hypoxia protein ligase

WEE1 WEE1 WEE1 WEE1 G2 checkpoint kinase Wee 1 Cell Signaling 4936 Rabbit 0.5-0.7 1000 20000 CellCycle

WTAP WTAP WTAP Wilms tumor 1 associated protein WTAP Sanjay Bansal from UTSA Rabbit > 0.7 20000 20000 CellCycle, FLI1, Histone

XPO1 XPO1 XPO1 exportin 1 (CRM1 homolog, yeast) CRM1 Santa Cruz sc-5595 Rabbit > 0.7 3000 20000 Cytoskeletal

YAP1 YAP1 YAP1 Yes-associated protein 1 YAP Cell Signaling 4912 Rabbit 0.5-0.7 300 20000 ApopReg, HIPPO YAP1 phospho Serine YAP1.p YAP1 Yes-associated protein 1 Inactivation YAP-p(ser127) Cell Signaling 4911 Rabbit 0.5-0.7 1000 20000 ApopReg, HIPPO 127

YES1 YES1 YES1 YES proto-oncogene 1 Yes-1 Abcam ab133314 Rabbit > 0.7 5000 20000 HIPPO, SRC

tyrosine 3-monooxygenase/tryptophan 5- YWHAZ YWHAZ YWHAZ monooxygenase activation protein, zeta 14-3-3-zeta Chemicon AB9746 Rabbit > 0.7 1500 20000 TP53 polypeptide Supplementary Table S3. Protein membership for the 31 defined protein functional groups.

Protein Number of Functional Antibodies Antibodies Group CAV1, FN1, IGFBP2, ITGA2, ITGAL, ITGB3, PTK2, Adhesion 9 SPP1, TGM2 BAD, BAK1, BAX, BCL2, BCL2L1, BCL2L11, BID, Apoptosis BH3 8 MCL1 Apoptosis IAP 4 BIRC2, BIRC5, DIABLO, XIAP CASP3, CASP3.cl175, CASP7.cl198, CASP8, Apoptosis 9 CASP9, CASP9.cl315, CASP9.cl330, PARP1, Occurring PARP1.cl214 Apoptosis 4 TP53, TP53.pS15, YAP1, YAP1p Regulating ATF3, BECN1, PARK7, SQSTM1, STK11, TSC2, Autophagy 7 TSC2.pT1462 BRCA2, CCNB1, CCND1, CCND3, CCNE1, CCNE2, CDK1, CDK2, CDK4, CDKN1A, CDKN1B, Cell Cycle 20 CDKN1B.pS10, CDKN2A, FKHRL1, FOXO3A, MYC, RB1, RB1.pS807_811, WEE1, WTAP CREB 4 ATF3, BECN1, CREB1, CREB1.pS133 Cytoskeletal 4 NF2, NF2.pS518, NRP1, XPO1 Differentiation 6 GATA1, GATA3, PIM1, PIM2, PPARG, SSBP2 FLI1 5 FLI1, NCL, NPM1.3542, STMN1, WTAP Heat shock 2 HSPB1, GRP78 BRCA2, NF2, NF2.pS518, TAZ, TAZ.pS89, YAP1, HIPPO 8 YAP1p, YES1 BMI1, CLPP, DDX17, FLI1, H3K4Me2, H3K4Me3, Histone H3K27Me3, HDAC1, HDAC2, HDAC3, HDAC6, 18 modification HIST3H3, HNRNPK, NCL, SIRT1, KDM1A, TRIM24, WTAP Hypoxia 4 HIF1A, KDR, VASP, VHL MAP2K1, MAPK1, MAPK9, MAPK14, MAPK 5 MAPK14.pT180Y182 MEK 6 BRAF, DUSP6, ELK1.pS383, KIT, LYN, TNK1 Metabolic 2 ASNS, ODC1 EGFR, INPP5D, INPPL1, IRS1.pS1101, MTOR, MTOR.pS2448, PDK1, PDK1.pS241, PIK3CA, mTOR 16 PIK3R1_2, PTEN, RICTOR, RICTOR.pT1135, RPTOR, TSC2, TSC2.pT1462 AKT1, AKT1_2_3.pS473, AKT1_2_3.pT308, PI3KAKT 8 ELK1.pS383, FKHRL1, FOXO3A, GAB2, GAB2.pY452 PRKCA, PRKCA.pS657, PRKCB.I, PRKCD.pS645, PKC 5 RELA DDX17, MSI2, RICTOR, RICTOR.pT1135, RPS6, Ribosome 10 RPS6.pS235_236, RPS6.pS240_244, RPS6KB1, RPS6KB1.pT389, RPTOR SMAD1, SMAD2, SMAD2.pS245, SMAD2.pS465, SMAD 9 SMAD3, SMAD4, SMAD5, SMAD5.pS463, SMAD6 SRC 3 SRC, SRC.pY416, YES1 MAPK9, STAT1, STAT1.pY701, STAT3, STAT 9 STAT3.pS727, STAT3.pY705, STAT5A_B, STAT5A_B.pY694, STAT6.pY641 EGFR, ERBB2, ERBB2.pY1248, IGF1R, KIT, LYN, STP Upstream 9 MET.pY1230_1234_1235, PTPN11, SOCS2 T-cell 5 CD74, LCK, LGALS3, NOTCH1.cl1744, NOTCH3 IRS1.pS1101, MDM2, MDM4, SFN, TP53, TP53 8 TP53.pS15, TRIM24, YWHAZ DDX17, DLX1, EIF2AK2, EIF2AK2.pS51, Transcription 15 EIF2AK2.pT451, EIF2S1, EIF4E, GATA1, GATA3, JUN.pS73, JUNB, MYC, NR4A1, SPI1, TCF4 Ubiquitin 4 CBL, ERN1, GRP78, TRIM24 Wnt signaling 3 CTNNA1, CTNNB1, LEF1

Supplementary Table S4. ALL protein constellation membership for the 114 protein clusters.

Constellation Protein cluster 4 ApopRegC3 1 ApopOccurC1 4 AutophagyC4 1 BH3C3 4 CREBC4 1 PI3KAKTC1 4 CytoskeletalC3 1 STATC1 4 HeatshockC1 2 AdhesionC4 4 HIPPOC3 2 CellCycleC1 4 HistoneC4 2 DifferentiationC2 4 HypoxiaC2 2 Fli1C5 4 IAPC3 2 HypoxiaC3 4 MAPKC4 2 MetabolicC2 4 mTORC2 2 PKCC3 4 RibosomeC4 2 SRCC3 4 SMADC3 2 STPC1 4 TP53C4 2 UbiquitinC3 4 TranscriptionC1 2 WntC1 4 UbiquitinC1 2 WntC2 5 AdhesionC3 3 CREBC3 5 ApopOccurC3 3 DifferentiationC3 5 AutophagyC3 3 DifferentiationC4 5 CellCycleC2 3 Fli1C2 5 HeatshockC4 3 Fli1C4 5 HistoneC3 3 IAPC1 5 MEKC2 3 MAPKC3 5 MetabolicC3 3 mTORC3 5 PKCC4 3 TcellC3 5 SMADC2 3 TP53C3 5 SRCC4 3 TranscriptionC3 5 WntC4 3 UbiquitinC4 6 AutophagyC2 6 CREBC5 8 AutophagyC1 6 CytoskeletalC1 8 CREBC2 6 HIPPOC1 8 CytoskeletalC2 6 IAPC2 8 HeatshockC3 6 MAPKC2 8 HIPPOC2 6 MetabolicC4 8 IAPC4 6 mTORC4 8 MAPKC1 6 PI3KAKTC3 8 MEKC3 6 PKCC1 8 MetabolicC1 6 RibosomeC1 8 PKCC2 6 TP53C2 8 RibosomeC3 6 TranscriptionC4 8 SRCC2 7 AdhesionC1 8 STATC2 7 AdhesionC2 8 TranscriptionC2 7 ApopOccurC2 9 ApopRegC1 7 BH3C2 9 HypoxiaC1 7 CREBC1 9 STPC3 7 Fli1C3 10 BH3C1 7 HeatshockC2 10 CellCycleC3 7 HistoneC2 10 DifferentiationC1 7 MEKC1 10 Fli1C1 7 PI3KAKTC2 10 HistoneC1 7 RibosomeC2 10 mTORC1 7 SMADC4 10 SMADC1 7 SRCC1 10 TcellC2 7 STATC3 10 TP53C1 7 STPC2 10 UbiquitinC2 7 TcellC1 10 WntC3 8 ApopRegC2 Supplementary Table S5. T-ALL protein constellation membership for the 114 protein clusters.

Constellation Protein cluster 2 AdhesionC4 1 ApopOccurC1 2 ApopOccurC2 1 ApopOccurC3 2 ApopRegC2 1 AutophagyC1 2 ApopRegC3 1 CREBC2 2 AutophagyC2 1 CREBC3 2 AutophagyC4 1 CREBC5 2 BH3C1 1 CytoskeletalC1 2 BH3C2 1 CytoskeletalC2 2 CellCycleC1 1 DifferentiationC3 2 CREBC1 1 DifferentiationC4 2 CREBC4 1 HeatshockC3 2 CytoskeletalC3 1 HIPPOC1 2 DifferentiationC1 1 HIPPOC2 2 DifferentiaionC2 1 MAPKC1 2 Fli1C1 1 MAPKC3 2 Fli1C3 1 MetabolicC3 2 Fli1C5 1 MetabolicC4 2 HeatshockC1 1 mTORC2 2 HeatshockC2 1 mTORC3 2 HIPPOC3 1 PKCC1 2 HistoneC1 1 PKC4 2 HistoneC2 1 RibosomeC1 2 HistoneC4 1 STATC1 2 HypoxiaC2 1 STATC2 2 HypoxiaC3 1 WntC3 2 IAPC2 1 WntC4 2 IAPC3 2 AdhesionC1 2 MAPKC2 2 AdhesionC2 2 MAPKC4 2 MEKC1 2 UbiquitinC1 2 MEKC3 2 UbiquitinC2 2 MetabolicC1 2 UbiquitinC3 2 MetabolicC2 2 WntC1 2 mTORC1 2 WntC2 2 mTORC4 3 CellCycleC3 2 PI3KAKTC2 3 Fli1C2 2 PI3KAKTC3 3 IAPC4 2 PKCC2 4 AdhesionC3 2 PKCC3 4 ApopRegC1 2 RibosomeC2 4 AutophagyC3 2 RibosomeC4 4 HeatshockC4 2 SMADC1 4 HistoneC3 2 SMADC3 4 RibosomeC3 2 SMADC4 4 SRCC4 2 SRCC1 4 STPC3 2 SRCC2 4 TcellC3 2 SRCC3 4 TP53C3 2 STATC3 4 UbiquitinC4 2 STPC1 5 BH3C3 2 STPC2 5 CellCycleC2 2 TcellC1 5 Fli1C4 2 TcellC2 5 IAPC1 2 TP53C1 5 MEKC2 2 TP53C2 6 HypoxiaC1 2 TP53C4 6 PI3KAKTC1 2 TranscriptionC1 6 SMADC2 2 TranscriptionC2 6 TranscriptionC3 2 TranscriptionC4

Supplementary Table S6. B-ALL protein constellation membership for the 114 protein clusters.

Constellation Protein Cluster 4 ApopRegC1 1 AdhesionC4 4 AutophagyC1 1 CellCycleC1 4 CREBC1 1 DifferentiationC2 4 CREBC2 1 Fli1C5 4 CytoskeletalC2 1 MetabolicC2 4 Fli1C1 1 PKCC3 4 HeatshockC3 1 SRCC3 4 HIPPOC2 1 WntC1 4 HistoneC1 1 WntC2 4 IAPC4 2 BH3C2 4 MAPKC1 2 HeatshockC2 4 MetabolicC1 2 HypoxiaC3 4 mTORC1 2 MEKC1 4 PKCC1 2 RPS6C2 4 RPS6C3 2 SMADC4 4 SRCC2 2 SRCC4 4 TP53C1 2 STPC2 4 TranscriptionC2 2 UbiquitinC4 5 ApopRegC3 3 BH3C1 5 AutophagyC4 3 CellCycleC3 5 CREBC4 3 DifferentiationC1 5 CytoskeletalC3 3 HypoxiaC1 5 HeatshockC1 3 SMADC1 5 HIPPOC3 3 STPC3 5 HistoneC4 3 TcellC2 5 HypoxiaC2 3 UbiquitinC2 5 IAPC3 3 WntC3 5 MAPKC4 4 AdhesionC1 5 mTORC2 5 RPS6C4 7 RPS6C1 5 SMADC3 7 STATC3 5 STPC1 7 TP53C2 5 TP53C4 7 TranscriptionC4 5 TranscriptionC1 8 PKCC4

5 UbiquitinC1 8 SRCC1 6 AdhesionC2 9 CREBC3 6 ApopOccurC1 9 DifferentiationC3 6 BH3C3 9 DifferentiationC4 6 MEKC3 9 mTORC3 6 PI3KAKTC1 9 TcellC3 6 PI3KAKTC2 9 TP53C3 6 PKCC2 9 TranscriptionC3 6 STATC1 10 ApopOccurC3 6 STATC2 10 AutophagyC3 6 TcellC1 10 CellCycleC2 7 AdhesionC3 10 Fli1C2 7 ApopOccurC2 10 Fli1C3 7 ApopRegC2 10 Fli1C4 7 AutophagyC2 10 HistoneC2 7 CREBC5 10 HistoneC3 7 CytoskeletalC1 10 IAPC1 7 HeatshockC4 10 MAPKC3 7 HIPPOC1 10 MEKC2 7 IAPC2 10 MetabolicC3 7 MAPKC2 10 SMADC2 7 MetabolicC4 10 UbiquitinC3 7 mTORC4 10 WntC4 7 PI3KAKTC3

Supplementary Table S7. This table shows all variables considered in the univariate Cox Proportional Hazard Model. Only variables that had sufficient data available were considered in the model. Similar to what has traditionally been done with cytogenetics, the 7 signatures were lumped together into signatures that had a favorable (signature 2, 4), an intermediate (signature 1, 3, and 6), or an unfavorable (signature 5, 7) outcome on survival. None of the variables were significant.

Beta 95% CI for HR Wald test P-value Favorable signatures (2, 4) -1.1 0.35 (0.044-2.7) 1 0.32 Intermediate signatures (1, 3, 6) -0.11 0.9 (0.26-3.1) 0.03 0.86 Unfavorable signatures (5, 7) 0.8 2.2 (0.63-7.9) 1.5 0.21 Age 0.032 1 (0.91-1.2) 0.26 0.61 Sex 0.27 1.3 (0.37-4.6) 0.17 0.68 ALL Type -0.11 0.89 (0.19-4.2) 0.02 0.89 Ethnicity 0.98 2.7 (0.75-9.4) 2.3 0.13 Favorable Cytogenetics -19 3.8e-09 (0-Inf) 0 1 Intermediate Cytogenetics 0.97 2.6 (0.55-13) 1.5 0.23 Unfavorable Cytogenetics 0.043 1 (0.22-5) 0 0.96 CDKN2A mutation 0.9 2.5 (0.61-9.8) 1.6 0.2 High risk group 1.2 3.4 (0.72-16) 2.4 0.12 Intermediate risk group -1 0.36 (0.077-1.7) 1.6 0.2 Low risk group -17 3.8e-08 (0-Inf) 0 1 WBC 0.0015 1 (1-1) 3.3 0.068 Absolute Blast count PB 0.00 1 (1-1) 0.07 0.79 % BM blasts -0.007 0.99 (0.95-1) 0.08 0.78 Platelet count 0.0032 1 (0.99-1) 0.23 0.63

Supplementary Table S8. Protein cluster membership for the leukemic cell lines. Cell line Disease Age ViabilityAdhesionApopOccurApopRegBH3 IAP AutophagyCellCycleCREB CytoskeletalDifferentiationFLI1 HeatshockHIPPO HistoneHypoxiaMAPK MEK MetabolicmTOR PI3KAKTPKC RPS6 SMAD SRC STAT STP TCELL TP53 TranscriptionUbiquitinWNT Blin-1 B-ALL Adult 99.7 − 1 − − 1,2 1 − − − − − − − − − − − − − − − − − − − − − − − − 4 BV173 Pre-B ALL Adult 96.9 − − − − 2 3 − − − − − − − − 3 − − 2 − − − − − − − − − − − 1 − BV173 treated Pre-B ALL Adult 97.2 − − − − 2,4 1 − − − − − − − − 3 − − 2 − − − − − − − − − − − 1 − CCRF-CEM T-ALL Pediatric 99.1 − 1 − 1 1,2,4 1 − 1,2 − − 4 − − − − − − 2 − − − − 2 − − − 2 − − − − Daudi Burkitt's lymphomaPediatric 95.6 − − − 3 1,2 − − − − − − − − − − 4 − − − − − − − − 1 − − − − − 2 GM00131 B-cells Adult 96.6 − 1,2 − 1 1,2 − − − − 2 3 − − − − 4 − − − − − − 4 − − − 2 − − 1 − GM00131 treated B-cells Adult 96 − 1 − 1 1 − − − − − − 1 − − − 4 − − − − − − 4 − − − 2 − − 1 1 HL-60 AML M2 Adult 91 − 1 − − 1,2,4 − − 1,2 − 2 − − − − − − − − − − 3 − 2 − 1 − − − − − − HL-60 AML M2 Adult 96.4 − 1 − − 1,2 − − − − 2 − − − − − − − − − − − − 2 − 1 − − − − − 2 HL-60 TRE TGM2 AML M2 Adult 93.3 − 1,2 − − 2 − − 5 − − − − − − − − − − − 1 − − 2 − 1 − − − − − 2 HL-60 TRE TGM2 controlAML M2 Adult 94.6 − 1 − − 1,2,4 − − − − − − − − − − − − − − − − − 2 − 1 − − − − − 2 HL-60 treated AML M2 Adult 95.4 − 1 − 2 1,2,4 − − − − 2 − − − − − − − − − 1 − − − − 1 − − 1,2 − − − JeKo-1 lymphoma Adult 98.1 − 1 − 3 1,2,4 − − − − − 2 − − − − 4 − − − − − − − − 1 − − − − − 2 Jurkat T-ALL Pediatric 98.6 − 1 − − 2 1,3 − 1,2 − − − − − − − − − 2 − − − − − − − − − − − 1 − Jurkat I9.2 Caspase8 mutT-ALL Pediatric 97.9 − 1 − − 1,2,4 − − 1 − − 4 − − − 3 2 − 2 − − 3 − − 3 − − − − − 1 − Jurkat treated T-ALL Pediatric 96.9 − 1 − − 2,4 − − 1 − − 4 − − − 3 − − 2 − − − − − 2 1 − − − − 1 − K562 CML Adult 96.4 − − − − 1,2,4 − − 1,2 − − − − − − − − − − − − − − − − − − − − − − 1 K562 treated CML Adult 92.5 − − − − 1,2 − − 5 − − − − − − − − − − − − − − − 4 − − − − − 1 1 Kasumi-1 AML M2 Pediatric 93 − 2 − 2 1,2 − − 1 − 2 − − − − 1 − − 2 − − 2 − − − − − − − − − 2 Kasumi-1 treated AML M2 Pediatric 94.4 − 1 − 2 − − − 1 − 2 − − − − − − − 2 − 1 3 − 2 − 1 − − − − − − KBM3 AML M5 Pediatric 96.9 − 1 − − − − − 1 − − − − − − − − − 2 − − − − 2 − 3 − − − − − 2 KBM5 CML Adult 94.3 − 1 − − − − − − − − 1 − − − − − − − − − − − 2 − − − − − − 1 2 KBM5 STI treated, w/o STICML T315I Adult 97.8 − 1 − − − − − − − − − − − − − − − − − 1 − − − − − − − − − − 2 KBM5 STI, w/o STI CML T315I Adult 98.8 − 1 − − 2 − − − − − 1 − − − − − − − − − − − − − − − − − − − 2 KBM5 STI, w/STI CML T315I Adult 97.5 − 1 − − − − − 1 − − − − − − 1 − − − − − − − − − − − − − − − 2 KBM5 treated CML Adult 95.5 − 1 − − 1,2 − − − − − − − − − − − − − − 1 − − − − − − − − − 1 2 KG-1 AML M3 Adult 95.9 − 1 − 1 1 2 − − − − 2 − − − 3 − − 2 − − − − − − − − 2 − − − − KG-1 AML M3 Adult 95.1 − 2 − 1,2 1,2 2 − − − − 2 − − − − − − − − − − − − − − − 2 − − − − KG-1 treated AML M3 Adult 96.6 − 1 − − 1,2 − − 1 − 2 − − − − 1 − − − − − 3 − − 1 1,2 − − − − − 2 KOPTI-K1 (lable:KOPTI) (Teresa label: KOPTI ALL)T-ALL Pediatric 97.2 − 1 − − − 3 − 1 − − 4 − − − 1 − − 2 − − 3 − 2 − − − 2 − − 1 − M-07e AML M7 Pediatric 92 − 1 − − 1,2,4 − − 1 − − − − − − − − − 2 − 1 − − − − − − − − − − − MDSL MDS Adult 94.1 − 1 − − 1,2 − − 1 − − 1 − − − 3 − − 2 − − 3 − − − − − − − − − 2 MINO Mantle Cell LymphomaAdult 94.5 − 2 − − 1,2,4 − − − − 2 − − − − − 4 − − − 1 − − − − − − 1,2 − − − 3 ML-1 AML M3 Adult 95.1 − 1 − − − − − 1 − − − − − − 3 − − − − − − − − − 1 − − − − − 2 ML-1 treated AML M3 Adult 94 − − − 3 1,2,4 − − 1,2 − − − − − − − − − − − 1 − − − − 3 − − − − − 1 ML-2 (AML-ML2) AML M4 Adult 98.4 − − − − − − − − − − − − − − 3 − − − − − − − − − − − − − − − 2 Molm13 AML M5a Pediatric 92 − − − − 1,2 − − 1 − − − 1 1 − − − − − − − − − − − − − 2 − − 1 2 Molm13 P53 K/D AML M5a Pediatric 95.7 − 1 − − 1,2,4 − − 1 − − 1 − − − − 2 − − − 1 − − − 4 − − − 1 − 1 2 Molm13 P53 vector AML M5a Pediatric 96.5 − 1 − − − − − 1 − − 1 − − − − − − − − − − − − − − − − − − 1 2 Molm14 AML M5a Pediatric 98 − 1 − − 2 3 − 1 − 2 1 1 − − − − − − − − − − − − 3 − − − − 1 2 Molm14 AML M5a Pediatric 98 − 1 − − 1,2 − − 1 − − − − − − 1 − − − − − − − − 4 3 − − − − 1 2 Molm14 treated AML M5a Pediatric 98.7 − 1 − − − − − 1 − − − − − − − − − − − 2 − − − − − − − − − 1 2 Molt3 T-ALL Pediatric 93.6 − 1 − 1,2 2 1,3 − − − − 4 − − − − − − 2 − − 2 − − − − − − − − − 4 Molm16 AML, M0 Adult 93.8 − 1 − − 1,2,4 1 − − − − − − − − − − − − − − 2 − − − − − − − − 1 − Molt4 T-ALL Pediatric 94.8 − 1 − − − 3 − − − − 4 − − − − − − 2 − 1 3 − − − − − 2 − − − − MR2 treated AML, M3 Adult 93.1 − 1,2 − − 1,2,4 − − − − − − − − − 1 − − 2 − − − − − − 1 − − − − − 2 MV4-11 AML M5 Pediatric 93 − 1 − − 1,2 − − 1 − − − − − − 3 2 − − − − − − − − 3 − − − − 1 2 MV4-11 IDH1 R132H AML M5 Pediatric 91 − 1,2 − − 1,2 − − 1 − − − − − − − − − 2 − − − − − − − − − − − − 2 MV4-11 IDH1 wt(vector)AML M5 Pediatric 91.1 − 1,2 − − 2 − − 1 − − − − − − − − − − − − − − − − 1 − − − − − 2 MV4-11 treated AML M5 Pediatric 91 − − − − − − − 1 − − − − − − − − − − − − − − − − 3 − − − − 1 2 Nalm6 treated Pre-B ALL Pediatric 98.5 − 1 − − 1,2,4 − − − − − − − − − − − − 2 − − − − − − 1 − 1 − − − 4 NB4 AML M3 Adult 94 − 1,2 − − − − − − − − − − − − − − − 2 − 1 − 1 − − 1 − − − − − 2 OCIAML2 AML M4 Adult 96.2 − 1 − 2 − 2,3 − 1 − − 1 − − − 1,3 − − − − − − − − − 1 − − − − − − OCIAML3 AML M4 Adult 93.6 − 1 − − 1,2,4 − − − − − − − − − − − − − − 1 − − − − − − − − − 1 − OCIAML3 550 TGM2-overexpAML M4 Adult 97 − 1 − − − − − 1 − − − − − − − − − − − − − − − − − − − − − 1 2 OCIAML3 708 ppp2R2A shRNAAML M4 Adult 95.4 − 1 − − 2,4 − − − − − − − − − − − − 2 − − − − − − − − − − − − 2 OCIAML3 709 ppp2R2A shRNAAML M4 Adult 99 − 1 − − 1,2 − − − − − 1 − − − − − − − − − − − − − 1 − − − − − 2 OCIAML3 Bcl2 overexpressionAML M4 Adult 94.3 − 1 − 2 − − − 1 − 2 3 − − − − − − − − − − − − − 1 − − − − − 2 OCIAML3 Bcl2 vector AML M4 Adult 93.9 − 1 − 2 1,2,4 − − − − 2 3 − − − − − − − − − − − − 1 − − − − − − 2 OCIAML3 IDH1 R132H AML M4 Adult 98.5 − 1 − − 1,2 − − − − − 1 − − − − 1 − − − − − − − − 2 − − − − − − OCIAML3 IDH1 wt(vector)AML M4 Adult 94.5 − 1 − − − − − − − − − − − − − 1 − 2 − − − − − − 1 − − − − 1 2 OCIAML3 induxible HIF1a ODD mutAML M4 Adult 99 − 1 − − 1,2,4 − − − − 2 1 − − − 3 1 − 2 − − − − − − 1 − − − − − − OCIAML3 ITD treated AML M4 Adult 95.3 − 1 − − 1 − − 1 − − − − − − 3 − − − − 1 − − − − 1 − − − − − 2 OCIAML3 ITD vec AML M4 Adult 92 − 1 − − 2 − − − − − − − − − − − − 2 − 1 − − − − − − − − − − − OCIAML3 NS for ppp2R2A shRNAAML M4 Adult 97.3 − 1 − − 1,2,4 − − − − − − 1 − − − − − − − − − − − − − − − − − − − OCIAML3 p100SSAA AML M4 Adult 96.9 − 1 − − 1,2 − − 1 − − − − − − − 1 − − − 1 − − − − 1 − − − − 1 2 OCIAML3 P53 shRNA AML M4 Adult 98.2 − 1 − − − − − − − − − − − − − − − − − 1 − − − − − − 2 − − 1 − OCIAML3 P53 vector AML M4 Adult 97 − 1 − − 1 − − − − − − − − − 3 − − − − − − − − − − − − − − 1 − OCIAML3 PI3K active pool #1AML M4 Adult 97.5 − 1 − − 2,4 − − − − − 1 − − − − 1 − − − − − − − − 1 − − − − − − OCIAML3 PI3K wt pool#2 1AAML M4 Adult 99.1 − 1 − − 1,2,4 − − − − − − − − − − − − − − 1 − − − − 1 − − − − − − OCIAML3 Stat5A AML M4 Adult 97.5 − 1 − − 1,2 − − 1 − − 1 − − − − 1 − 2 − − − − − − 1 − − − − 1 2 OCIAML3 stat5A N642H AML M4 Adult 96.4 − 1 3 − 1,2,4 − − − − − 1 − − − − 1 − 2 − 1 − − − − 1 − 2 − − − 2 OCIAML3 stat5A N642H H4FAML M4 Adult 96.3 − 1 − − 1,2,4 − − − − − − 1 − − − 2 − 2 − − − − − − 1 − − − − − 2 OCIAML3 stat5A wt AML M4 Adult 98.9 − 1 − − 1,2,4 − − − − 2 1,3 − − − − − − − − − − − − − 2 − 2 − − − − OCIAML3 TRE TGM2 AML M4 Adult 97.8 − 1 − − 2 − − 1 − − 1 − − − − 2 − − − − − − − − − − − − − − 2 OCIAML3 TRE TGM2 control AML M4 Adult 99 − 1 − − 1,2,4 − − − − − 1 − − − 3 1 − − − − − − − − 1 − − − − − − OCIAML5 AML M4 Adult 98.1 − 1 − − − − − 1 − − 1 − − − − − − 2 − − − − 2 − 1 − − − − − 2 P12 ichikawa T-ALL Pediatric 98.4 − 1 − 2 1,2,4 3 − 1 − − 4 − − − 1 − − 2 − − 3 − 2 − − − − − − − 2 Raji Burkitt's lymphomaPediatric 98.7 − − − 2 1 − − − − − − − − − − 4 − − − − − − − − − − − − − − 2 Raji treated Burkitt's lymphomaPediatric 95.1 − 2 − − 1 − − − − 2 − − − − − − − − − − − − − − − − − − − 1 2 Ramos Burkitt's lymphomaPediatric 94.8 − − − 3 − − − 1 − − − − − − − − − − − − − − − − − − 2 − − 1 3 REH ALL (non-T; non-B)Pediatric 98.2 − 1 − 2 1,2,4 − − 1 − − 4 − − − − 4 − 2 − 1 − − − − − − − − − − − REH PLKO CTGF ALL (non-T; non-B)Pediatric 97 − − − 2 − − − 1 − − 2,4 − − − − − − 2 − − − 3 2 − 1 − − − − − − REH PLKO-NS-shRNA(control)ALL (non-T; non-B)Pediatric 98 − 1 − 2 2,4 − − 1 − − 2,4 − − − − − − 2 − − − − − − − − − − − 1 − REH treated ALL (non-T; non-B)Pediatric 99.1 − 1 − 2 2 − − 1 − − − − − − − − − 2 − 1 − − − − − − − − − 1 − RPMI8226 Myeloma Adult 91.7 − 2 − − 1,2,4 − − 5 − 2 − − − − − − − − − 1 − − − − − − − − − − − RS4:11 Pre-B ALL Adult 97.6 − − − − 1,2 − − − − − 4 − − − − − − − − 1 − − 2 − − − − − − − 4 RS4:11 Treated Pre-B ALL Adult 94.9 − 1 − − 1,2 1 − 1 − 2 2 − − − − 4 − − − 1 − − − − 1 − − − − − 3 SKM1 AML M5 Adult 93.5 − 2 − − − 2 − 1 − 2 − − − − 1 − − 2 − − − − − 1 − − − − − − − SR Large cell immunoblastic lymphoma Pediatric 90 − 2 − − 1,2,4 2 − 1 − 2 − − − − 2 − − − − − − − − 4 − − − − − − 2 TALL-1 T-ALL Adult 96.3 − 1 − 2 − 1,3 − − − − 4 − − − − − − − − − − − − − − − − − − − 3 TF-1 AML M6 Adult 92.7 − 1 − − − − − 1 − − − − − − − − − − − − − − − − − − − − − − − THP-1 AML M5 Pediatric 95.1 − 1 − − 1,2,4 − − 1 − − 1 − − − − − − − − 1 − − − − − − − − − − − U937 AML M5 Adult 92.5 − 1,2 − − 1,2,4 − − − − 2 − − − − − − − 2 − − − − − − 1 − − 1,2 − 1 2 U937 treated AML M5 Adult 95.8 − 2 − − 1 − − − − 2 − − − − − − − 2 − − − − − − − − − − − 1 2 Supplementary Figures

A Low Expression High Expression

A A A A A A F F F F F

S S S Pr ior Pathw ay Meta-Galaxy S S D Know ledge Analy s is Analy s is F C C C D C C S D D D D S S S S S C X X X X X X

Proteins PFG Protein Clusters Constellations

Clusters Correlations Correlations Survival Survival B. Pathway Analysis Clinical

Patients Survival Analysis & Clinical Correlations Time Progeny Proteins Proteins Clustering

PC1 PC1 Pediatric ALL CD34+

Principle Component Analysis

PC2 Cluster 1 Cluster 2 Cluster 3

Network Analysis

Clusters C. Meta-Galaxy Analysis Correlations Correlations Survival Survival Clinical Clinical

Signatures Patients

Survival Analysis & Clusters Clusters Co-Clustering Constellations Clinical Correlations Time

P P P P P P

P P P P

P P P P P Over Expressed Protein Presence Under Expressed Protein Absence Drug Target P P P P Discovery P P P P P

P P P P

Supplementary Fig. S1. Computational work flow. A) Overall work flow; B) Pathway analysis for each Protein Functional Group (PFG); C) Meta-galaxy analysis and target identification. A B

Co-occurrence Probability Matrix FLI1, K=5

Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10 Y11 Y12 Y13 Y14 Y15 Y16 Y17 Y18 Y19 Y20 Y21 Y22 Y23 Y24 Y25 Y26 Y27 Y28 Y29 Y30 Y31 Y32 Y33 Y34 Y35 Y36 Y37 Y38 Y39 Y40 Y41 Y42 Y43 Y44 Y45 Y46 Y47 Y48 Y49 Y50 Y1 0.6 0.6 0.7 0.6 0.6 0.6 0.6 0.5 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Y2 0.6 0.6 0.5 0.6 0.6 0.5 0.6 0.5 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Y3 0.6 0.6 0.6 0.7 0.6 0.7 0.6 0.6 0.8 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.3 0.2 0.3 0.6 0.1 0.0 0.2 0.3 Y4 0.7 0.5 0.6 0.7 0.7 0.6 0.7 0.6 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Y5 0.6 0.6 0.7 0.7 0.6 0.6 0.6 0.6 0.7 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.3 0.3 0.2 0.2 0.2 0.2 Y6 0.6 0.6 0.6 0.7 0.6 0.6 0.6 0.6 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.2 0.3 0.3 0.3 0.3 0.3 0.3 0.3 C Y7 0.6 0.5 0.7 0.6 0.6 0.6 0.6 0.6 0.6 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.3 0.2 0.3 0.2 0.2 1 Y8 0.6 0.6 0.6 0.7 0.6 0.6 0.6 0.6 0.7 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.3 0.3 0.3 0.3 0.2 0.1 0.6 0.2 0.0 0.1 Y9 0.5 0.5 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.2 0.2 0.3 0.3 0.3 Y10 0.6 0.6 0.8 0.6 0.7 0.6 0.6 0.7 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.3 0.2 0.2 Y11 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.7 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.0 0.1 0.0 0.0 0.1 0.0 Y12 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.7 0.5 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 Y13 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.6 0.5 0.6 0.7 0.6 0.6 0.6 0.6 0.5 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y14 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.6 0.6 0.6 0.6 0.7 0.6 0.6 0.6 0.6 0.2 0.3 0.2 0.3 0.3 0.3 0.3 0.2 0.3 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.0 0.0 0.0 0.1 0.0 0.1 0.1 0.1 0.0 0.2 0.8 0.1 0.0 Y15 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.7 0.6 0.7 0.7 0.6 0.6 0.6 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 Y16 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.6 0.7 0.7 0.7 0.7 0.7 0.7 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.0 0.1 0.0 0.0 0.1 0.1 C Y17 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.6 0.6 0.7 0.7 0.6 0.6 0.7 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.1 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 2 Y18 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.6 0.6 0.6 0.7 0.6 0.6 0.6 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.1 0.1 Y19 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.6 0.6 0.6 0.7 0.6 0.6 0.7 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 Y20 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.6 0.6 0.5 0.6 0.6 0.7 0.7 0.6 0.7 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.2 0.0 0.1 0.8 0.0 Y21 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.7 0.7 0.7 0.6 0.8 0.7 0.7 0.8 0.7 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y22 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.3 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.7 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y23 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.7 0.8 0.7 0.8 0.7 0.8 0.7 0.8 0.8 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y24 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.7 0.8 0.7 0.8 0.8 0.7 0.7 0.8 0.8 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y25 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.6 0.8 0.8 0.8 0.7 0.7 0.7 0.8 0.8 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.3 0.1 0.0 0.0 0.7 Y26 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.8 0.8 0.7 0.8 0.7 0.8 0.7 0.8 0.7 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 C3 Y27 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.3 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.7 0.8 0.8 0.7 0.7 0.8 0.7 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y28 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.1 0.7 0.8 0.7 0.7 0.7 0.7 0.7 0.8 0.8 0.1 0.2 0.1 0.1 0.2 0.2 0.1 0.1 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y29 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.8 0.8 0.8 0.8 0.8 0.8 0.7 0.8 0.8 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y30 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.3 0.3 0.2 0.3 0.3 0.2 0.2 0.2 0.3 0.2 0.7 0.8 0.8 0.8 0.8 0.7 0.7 0.8 0.8 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y31 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.8 0.8 0.8 0.8 0.9 0.9 0.8 0.8 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y32 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.8 0.8 0.8 0.8 0.9 0.9 0.8 0.9 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y33 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.8 0.8 0.8 0.7 0.8 0.9 0.9 0.8 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y34 0.2 0.2 0.2 0.1 0.2 0.1 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.8 0.8 0.8 0.8 0.8 0.8 0.9 0.8 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Color legend Y35 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.2 0.1 0.2 0.2 0.2 0.2 0.1 0.2 0.1 0.1 0.8 0.8 0.7 0.8 0.8 0.8 0.8 0.8 0.7 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y36 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.9 0.9 0.8 0.8 0.8 0.8 0.8 0.9 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 C4 Y37 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.9 0.9 0.9 0.8 0.8 0.8 0.8 0.8 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y38 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.8 0.8 0.9 0.9 0.8 0.8 0.8 0.8 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Y39 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.8 0.9 0.8 0.8 0.8 0.9 0.8 0.8 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y40 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.8 0.8 0.8 0.8 0.7 0.8 0.8 0.8 0.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y41 0.2 0.3 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 Y42 0.3 0.3 0.2 0.3 0.2 0.3 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.7 0.6 0.7 0.7 0.7 0.7 Y43 0.3 0.3 0.2 0.3 0.3 0.2 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.1 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 Y44 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.1 0.1 0.1 0.0 0.0 0.1 0.0 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.7 0.6 0.7 0.6 0.6 0.7 Y45 0.3 0.3 0.2 0.3 0.3 0.3 0.3 0.3 0.3 0.2 0.0 0.0 0.1 0.0 0.1 0.0 0.0 0.1 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.7 0.6 0.7 0.7 0.7 0.7 Y46 0.3 0.3 0.2 0.3 0.3 0.3 0.3 0.3 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.6 0.7 0.6 0.6 0.7 0.7 0.7 0.6 C5 Y47 0.3 0.3 0.2 0.3 0.2 0.3 0.2 0.3 0.2 0.2 0.0 0.1 0.1 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.6 0.6 Y48 0.3 0.3 0.3 0.3 0.2 0.3 0.3 0.3 0.3 0.3 0.0 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.6 0.7 0.7 0.7 0.7 0.6 Y49 0.3 0.3 0.2 0.3 0.2 0.3 0.2 0.3 0.3 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.6 0.7 0.7 0.6 0.7 0.7 Y50 0.3 0.3 0.3 0.3 0.2 0.3 0.2 0.2 0.3 0.2 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.7 0.7 0.7 0.7 0.6 0.6 0.6 0.7

C D

Co-occurrence Probability Matrix ApopOccur, K=3

Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10 Y11 Y12 Y13 Y14 Y15 Y16 Y17 Y18 Y19 Y20 Y21 Y22 Y23 Y24 Y25 Y26 Y27 Y28 Y29 Y30 Y1 0.7 0.7 0.7 0.8 0.7 0.7 0.7 0.8 0.7 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 Y2 0.7 0.7 0.7 0.8 0.7 0.7 0.7 0.8 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.3 0.2 0.3 0.3 0.3 0.3 0.2 0.2 Y3 0.7 0.7 0.8 0.8 0.7 0.7 0.7 0.7 0.8 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.3 0.3 0.3 0.2 0.2 0.7 0.1 0.2 Y4 0.7 0.7 0.8 0.7 0.7 0.7 0.7 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.3 0.2 0.3 0.3 0.2 0.3 0.3 0.3 0.2 Y5 0.8 0.8 0.8 0.7 0.8 0.7 0.8 0.8 0.8 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.1 Y6 0.7 0.7 0.7 0.7 0.8 0.7 0.7 0.8 0.8 0.2 0.2 0.2 0.1 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 C1 Y7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.3 0.3 0.3 0.3 0.3 0.2 0.2 Y8 0.7 0.7 0.7 0.7 0.8 0.7 0.7 0.7 0.7 0.1 0.2 0.2 0.1 0.2 0.1 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.1 0.9 0.0 Y9 0.8 0.8 0.7 0.7 0.8 0.8 0.7 0.7 0.8 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Y10 0.7 0.7 0.8 0.7 0.8 0.8 0.7 0.7 0.8 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.3 0.2 0.3 0.2 0.2 0.2 Y11 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.9 0.9 0.9 0.9 0.9 0.9 0.8 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y12 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.9 0.8 0.9 0.9 0.9 0.9 0.9 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y13 0.2 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.2 0.1 0.9 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.9 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.1 0.0 Y14 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.9 0.9 0.8 0.8 0.9 0.9 0.9 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.8 Y15 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.2 0.1 0.9 0.9 0.8 0.8 0.8 0.9 0.8 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y16 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.9 0.9 0.8 0.9 0.8 0.9 0.9 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 C2 Y17 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.9 0.9 0.8 0.9 0.9 0.9 0.8 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y18 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.8 0.9 0.8 0.9 0.8 0.9 0.8 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Y19 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.1 0.1 0.9 0.9 0.8 0.9 0.9 0.9 0.9 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 Y20 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.9 0.9 0.9 0.9 0.9 0.9 0.9 0.9 0.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Color legend Y21 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 Y22 0.2 0.2 0.2 0.3 0.1 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 Y23 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Y24 0.2 0.2 0.2 0.3 0.1 0.2 0.3 0.2 0.2 0.2 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.7 0.8 0.8 0.8 Y25 0.2 0.3 0.2 0.3 0.2 0.2 0.3 0.2 0.2 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.7 0.8 0.7 0.8 Y26 0.2 0.3 0.3 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.7 0.8 0.8 0.8 C3 Y27 0.3 0.3 0.3 0.3 0.2 0.2 0.3 0.3 0.2 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.7 0.7 0.7 0.8 0.7 0.8 Y28 0.2 0.3 0.3 0.3 0.2 0.2 0.3 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.7 0.8 Y29 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.8 0.8 0.8 0.8 0.7 0.8 0.7 0.7 0.8 Y30 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8

C1 C2 C3

Supplementary Fig. S2. The co-occurrence probability matrices are shown for the PFG ‘‘FLI1’’ (A-B) and ‘‘Apoptosis Occurring’’ (C-D). Matrices show the measure of stability used in the Progeny Clustering algorithm. This clustering method first assigns cluster membership to the full data set and then validates the clusters by constructing progenies out of the existing ones by taking features independently. Each matrix (A, C) represents the result for the optimal number of clusters and shows the average cluster results (iteration = 100, repeat = 10) of all mixed progenies that were generated. A matrix entry is 1 if two progenies are in the same cluster, and 0 if they are in a different cluster. For each cluster 10 progenies were generated, which are denoted as Y. If the cluster quality was higher the classification region is shown in darker red. False classification regions that contain progenies from different initial clusters are shown in blue. B and D show the median probability scores of all progenies within a given protein cluster. For instance, the median of the probability scores in FLI1 is 0.7 (range 0.6-0.8) and the median of the probability scores in Apoptosis Occurring is 0.8 (range 0.7-0.9), suggesting quite robust clustering.

A B

● ● 2011 ● ● < 24 4 ● 2012 4 ● >= 24 ● ●●●● ● ●●●● ● ● 2013 ● ●● ● ●● ● ● ● ● 2014 ● ● ● ● ● ● ● ● ● ● ● ● ● ● 2 ● 2 ● ●● ●● ●● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ●● 0 ● ●● ● 0 ● ●● ● ● ● ● ● ● ● ● ● ● ●

PC2 ● PC2 ● ● ● ● ● ● ● 2 ● ● 2 ● ● − ● − ● ● ● ● ● ● ● ● ● ● ● 4 4 − − ● ● ● ● ● ● ● ● ● ● ● ● 6 6

− ● − ●

−5 0 5 10 −5 0 5 10

PC1 PC1

Supplementary Fig. S3. Principal component analysis for the year of collection (2011 vs. 2012 vs. 2013 vs. 2014) (A), and for the processing time of the leukemic samples (<24h vs. ≥24h) (B). From here no separation between the samples was observed based on one of the variables.

A B

Sample 6 Sample ● pediatric ALL ●

BCL2 SPI1 RPS6.pS235_236 CD34+ ERN1 JUN.pS73 ALL GRP78 CDK4 STAT1.pY701 ● CTNNB1 SMAD2.pS465 4 ● CD74 SQSTM1 CD34+ HSPB1 BIRC5 ● CTNNA1 VHL LYN CDKN1A FN1 ● SMAD1 PRKCA.pS657 ITGB3

TGM2 5 KIT 2 ● TAF4 FOXO3A GATA1 NR4A1 LCK PRKCA CBL SRC.pY416 ● LEF1 ●●● CDKN1B.pS10 PARP1.cl214 ● CASP3.cl175 CASP7.cl198 0 STAT1 ● SRC PTK2 VASP KDR ● ● GATA3 ● CCND3 SIRT1 BCL2L11 ● ● NOTCH3 ● GAB2.pY452 ● H3K27Me3 ● CDKN1B ● ● PIK3CA −2 ● DUSP6 ● ● CDKN2A PC2 SMAD5 ● ● CAV1 IGFBP2 ITGA2 ● ● SFN ● ● ● ● 0 ● ATF3 ● ● ● EGFR ● ●● HIF1A ● CCNE1 ● ● CCNB1 ● ● ODC1 −4 ● ● CDK2 ● ● HDAC1 ● ● ● MSI2 ●● HDAC3 ● STAT3 ● ● ●● ● RPS6KB1.pT389 ● JUNB ●●●● ● IRS1.pS1101 ● MTOR.pS2448 YWHAZ PRKCB.I ● ASNS ● LGALS3 CASP9 PRKCD.pS645 ● BAK1 TP53 RB1.pS807_811 CASP3 ● STMN1 ● PARK7 STK11 NF2 BECN1 MTOR EIF2AK2 MAPK14 BID HDAC6 5 AKT1

EIF2S1 − EIF4E WTAP NPM1.3542 RPS6KB1 NCL RPS6 BRCA2 HDAC2 SMAD4 TAZ.pS89 H3K4Me3 ELK1.pS383 TRIM24 ITGAL DIABLO KDM1A STAT5A_B MYC WEE1 −5 0 5 10 IGF1R RICTOR.pT1135 TAZ CCNE2 PPARG MET.pY1230_1234_1235 YAP1p EIF2AK2.pT451 CLPP YES1 NF2.pS518 PC1 PIM2 XIAP TP53.pS15 RPTOR ERBB2.pY1248 INPP5D SMAD5.pS463 ERBB2 YAP1 NOTCH1.cl1744 CASP8 STAT6.pY641 TSC2.pT1462 MCL1 DLX1 BIRC2 NRP1 CCND1 PIM1 SMAD6 SOCS2 CDK1 SPP1 CREB1.pS133 SMAD3 AKT1_2_3.pT308 STAT5A_B.pY694 STAT3.pY705 STAT3.pS727 MAPK14.pT180Y182 AKT1_2_3.pS473 RPS6.pS240_244 SMAD2.pS245 PTEN PARP1 SSBP2 GAB2 PIK3R1_2 BMI1 FLI1 MDM4 XPO1 BAD HNRNPK DDX17 TNK1 SMAD2 EIF2AK2.pS51 RB1 PDK1.pS241 PDK1 MAPK1 MAP2K1 FKHRL1 BRAF RICTOR PTPN11 MAPK9 RELA INPPL1 TSC2 HIST3H3 CREB1 H3K4Me2 BCL2L1 BAX CASP9.cl330 CASP9.cl315 MDM2

Supplementary Fig. S4. (A) Unsupervised hierarchical clustering and (B) principal component analysis plot for the CD34+ cells (black) and the pediatric ALL patient samples (red) clearly distinguish the healthy subjects from the cohort of pediatric ALL patients. A B

Cluster 6 Cluster LEF1 CDKN1B.pS10 LCK SRC.pY416 C1 PARP1.cl214 CASP3.cl175 CASP7.cl198 GATA3 4 CCND3 C2 SIRT1 BCL2L11 NOTCH3 PRKCA STAT1 LEF1 H3K27Me3 C3 CDKN1B.pS10 CDKN1B LCK PIK3CA SRC.pY416 6 CDKN2A 2 PARP1.cl214 CBL CASP3.cl175 DUSP6 CASP7.cl198 IGF1R C4 GATA3 RICTOR.pT1135 CCND3 TAZ SIRT1 NRP1 BCL2L11 SMAD5.pS463 NOTCH3 MCL1 PRKCA C5 STAT1 BIRC2 H3K27Me3 4 DLX1 0 CDKN1B PIM2 PIK3CA XIAP CDKN2A NF2.pS518 CBL ERBB2.pY1248 DUSP6 INPP5D C6 IGF1R MET.pY1230_1234_1235 RICTOR.pT1135 TP53.pS15 TAZ JUNB NRP1 IRS1.pS1101 SMAD5.pS463 RPS6KB1.pT389 −2 MCL1 2 C7 BIRC2 INPPL1 DLX1 MTOR.pS2448 PIM2 YWHAZ XIAP PRKCB.I NF2.pS518 CASP8 ERBB2.pY1248 HDAC3 INPP5D STAT3 MET.pY1230_1234_1235 YAP1p TP53.pS15 CLPP JUNB 0 EIF2AK2.pT451 −4 IRS1.pS1101 CCNE2 RPS6KB1.pT389 PPARG INPPL1 YAP1 MTOR.pS2448 YWHAZ ERBB2 PRKCB.I RPTOR CASP8 SMAD6 HDAC3 YES1 STAT3 SOCS2 YAP1p CCND1 CLPP −2 PIM1 EIF2AK2.pT451 CDK1 CCNE2 SPP1 PPARG PDK1.pS241 YAP1 PDK1 ERBB2 MAPK1 RPTOR SMAD6 MAP2K1 YES1 FKHRL1 SOCS2 BRAF CCND1 RICTOR PIM1 −4 PTPN11 CDK1 MAPK9 SPP1 RELA PDK1.pS241 BCL2L1 PDK1 BAX MAPK1 CASP9.cl330 MAP2K1 CASP9.cl315 FKHRL1 MDM2 BRAF RICTOR HIST3H3 PTPN11 CREB1 MAPK9 H3K4Me2 RELA FLI1 BCL2L1 MDM4 BAX XPO1 CASP9.cl330 BAD CASP9.cl315 TSC2 MDM2 HNRNPK HIST3H3 DDX17 CREB1 TNK1 H3K4Me2 SMAD2 FLI1 EIF2AK2.pS51 MDM4 XPO1 RB1 BAD GAB2.pY452 TSC2 PTEN HNRNPK PARP1 DDX17 SSBP2 TNK1 GAB2 SMAD2 PIK3R1_2 EIF2AK2.pS51 MAPK14.pT180Y182 RB1 AKT1_2_3.pS473 GAB2.pY452 RPS6.pS240_244 PTEN SMAD2.pS245 PARP1 NOTCH1.cl1744 SSBP2 GAB2 STAT5A_B.pY694 PIK3R1_2 STAT3.pY705 MAPK14.pT180Y182 STAT3.pS727 AKT1_2_3.pS473 AKT1_2_3.pT308 RPS6.pS240_244 CREB1.pS133 SMAD2.pS245 SRC NOTCH1.cl1744 PTK2 STAT5A_B.pY694 SMAD3 STAT3.pY705 VASP STAT3.pS727 KDR AKT1_2_3.pT308 GATA1 CREB1.pS133 NR4A1 SRC KIT PTK2 SMAD3 TAF4 VASP GRP78 KDR BIRC5 GATA1 CTNNA1 NR4A1 HSPB1 KIT VHL TAF4 CTNNB1 GRP78 SMAD2.pS465 BIRC5 JUN.pS73 CTNNA1 CDK4 HSPB1 STAT1.pY701 VHL BCL2 CTNNB1 SMAD2.pS465 SPI1 JUN.pS73 RPS6.pS235_236 CDK4 FN1 STAT1.pY701 FOXO3A BCL2 SMAD1 SPI1 PRKCA.pS657 RPS6.pS235_236 ITGB3 FN1 TGM2 FOXO3A ITGA2 SMAD1 SFN PRKCA.pS657 ATF3 ITGB3 EGFR TGM2 HIF1A ITGA2 SFN STAT6.pY641 ATF3 TSC2.pT1462 EGFR ASNS HIF1A TP53 STAT6.pY641 CCNB1 TSC2.pT1462 ODC1 ASNS BAK1 TP53 CASP9 CCNB1 PARK7 ODC1 STK11 BAK1 LGALS3 CASP9 BID PARK7 STK11 PRKCD.pS645 LGALS3 ERN1 BID CCNE1 PRKCD.pS645 SQSTM1 ERN1 CDK2 CCNE1 HDAC1 SQSTM1 MSI2 CDK2 SMAD5 HDAC1 CAV1 MSI2 IGFBP2 SMAD5 ITGAL CAV1 MYC IGFBP2 ITGAL WEE1 MYC CD74 WEE1 LYN CD74 CDKN1A LYN RB1.pS807_811 CDKN1A CASP3 RB1.pS807_811 STMN1 CASP3 NCL STMN1 RPS6KB1 NCL NF2 RPS6KB1 RPS6 NF2 BECN1 RPS6 MTOR BECN1 MTOR EIF2AK2 EIF2AK2 HDAC6 HDAC6 AKT1 AKT1 EIF2S1 EIF2S1 EIF4E EIF4E MAPK14 MAPK14 DIABLO DIABLO KDM1A KDM1A STAT5A_B STAT5A_B BMI1 BMI1 NPM1.3542 NPM1.3542 WTAP WTAP BRCA2 BRCA2 HDAC2 HDAC2 SMAD4 SMAD4 TAZ.pS89 TAZ.pS89 H3K4Me3 H3K4Me3 ELK1.pS383 ELK1.pS383 TRIM24 TRIM24

Supplementary Fig. S5. (A) Unsupervised hierarchical clustering for all proteins and ALL patients. (B) The Progeny Clustering algorithm (in combination with k-means).

Protein Expression Signature

ALL−Type Gender Age Risk Group CNS N=16 S6 S7 N=4 Cytogenetics Ethnicity SNP Ethnicity CDKN2A S1 S2 S3 S4 S5 S6 S7

ApopOccurC1ApopOccurC1 BH3C3BH3C3 ApopOccurC1PI3KAKTC1PI3KAKTC1 C1 STATC1STATC1 BH3C3AdhesionC4AdhesionC4 CellCycleC1CellCycleC1 PI3KAKTC1DifferentiationC2DifferentiationC2 STATC1Fli1C5Fli1C5 HypoxiaC3HypoxiaC3 AdhesionC4MetabolicC2MetabolicC2 PKCC3PKCC3 C2 CellCycleC1SRCC3SRCC3 DifferentiationC2STPC1STPC1 UbiquitinC3UbiquitinC3 Fli1C5WntC1WntC1 WntC2WntC2 HypoxiaC3CREBC3CREBC3 DifferentiationC3DifferentiationC3 MetabolicC2DifferentiationC4DifferentiationC4 PKCC3Fli1C2Fli1C2 Fli1C4Fli1C4 SRCC3IAPC1IAPC1 MAPKC3MAPKC3 C3 STPC1mTORC3mTORC3 UbiquitinC3TcellC3TcellC3 TP53C3TP53C3 WntC1TranscriptionC3TranscriptionC3 UbiquitinC4UbiquitinC4 WntC2ApopRegC3ApopRegC3 AutophagyC4AutophagyC4 CREBC3CREBC4CREBC4 CytoskeletalC3CytoskeletalC3 DifferentiationC3 Cluster Group Functional Protein HeatshockC1HeatshockC1 DifferentiationC4HIPPOC3HIPPOC3 HistoneC4HistoneC4 Fli1C2HypoxiaC2HypoxiaC2 Fli1C4IAPC3IAPC3 C4 MAPKC4MAPKC4 IAPC1mTORC2mTORC2 RPS6C4RPS6C4 MAPKC3SMADC3SMADC3 mTORC3TP53C4TP53C4 TranscriptionC1TranscriptionC1 C4 TcellC3UbiquitinC1UbiquitinC1 AdhesionC3AdhesionC3 TP53C3ApopOccurC3ApopOccurC3 AutophagyC3AutophagyC3 TranscriptionC3CellCycleC2CellCycleC2 HeatshockC4HeatshockC4 UbiquitinC4HistoneC3HistoneC3 C5 ApopRegC3MEKC2MEKC2 MetabolicC3MetabolicC3 AutophagyC4PKCC4PKCC4 SMADC2SMADC2 CREBC4SRCC4SRCC4 CytoskeletalC3WntC4WntC4 AutophagyC2AutophagyC2 HeatshockC1CREBC5CREBC5 CytoskeletalC1CytoskeletalC1 HIPPOC3HIPPOC1HIPPOC1 IAPC2IAPC2 HistoneC4MAPKC2MAPKC2 HypoxiaC2MetabolicC4MetabolicC4 C6 mTORC4mTORC4 N=16 IAPC3PI3KAKTC3PI3KAKTC3 PKCC1PKCC1 MAPKC4RPS6C1RPS6C1 TP53C2TP53C2 mTORC2TranscriptionC4TranscriptionC4 RPS6C4AdhesionC1AdhesionC1 AdhesionC2AdhesionC2 SMADC3ApopOccurC2ApopOccurC2 BH3C2BH3C2 Protein Constellation Constellation Protein TP53C4CREBC1CREBC1 TranscriptionC1Fli1C3Fli1C3 HeatshockC2HeatshockC2 UbiquitinC1HistoneC2HistoneC2 MEKC1MEKC1 C7 AdhesionC3PI3KAKTC2PI3KAKTC2 RPS6C2RPS6C2 ApopOccurC3SMADC4SMADC4 AutophagyC3SRCC1SRCC1 STATC3STATC3 CellCycleC2STPC2STPC2 TcellC1TcellC1 HeatshockC4ApopRegC2ApopRegC2 HistoneC3AutophagyC1AutophagyC1 CREBC2CREBC2 MEKC2CytoskeletalC2CytoskeletalC2 HeatshockC3HeatshockC3 MetabolicC3HIPPOC2HIPPOC2 IAPC4IAPC4 PKCC4MAPKC1MAPKC1 SMADC2MEKC3MEKC3 C8 MetabolicC1MetabolicC1 SRCC4PKCC2PKCC2 RPS6C3RPS6C3 WntC4SRCC2SRCC2 STATC2STATC2 AutophagyC2TranscriptionC2TranscriptionC2 CREBC5ApopRegC1ApopRegC1 HypoxiaC1HypoxiaC1 C9 CytoskeletalC1STPC3STPC3 BH3C1BH3C1 HIPPOC1CellCycleC3CellCycleC3 IAPC2DifferentiationC1DifferentiationC1 Fli1C1Fli1C1 MAPKC2HistoneC1HistoneC1 mTORC1mTORC1 MetabolicC4SMADC1SMADC1 C10 TcellC2TcellC2 mTORC4TP53C1TP53C1 PI3KAKTC3UbiquitinC2UbiquitinC2 PKCC1WntC3WntC3 RPS6C1 TP53C2 TranscriptionC4 AdhesionC1 AdhesionC2 ApopOccurC2 BH3C2 CREBC1 Fli1C3 HeatshockC2 HistoneC2 MEKC1 PI3KAKTC2 RPS6C2 SMADC4 SRCC1 Example 1: Constellation 4, signatureSTATC3 7 STPC2 TcellC1 ApopRegC2 AutophagyC1 CREBC2 CytoskeletalC2 HeatshockC3 HIPPOC2 IAPC4 MAPKC1 MEKC3 MetabolicC1 - Expected frequency C4: 107 /PKCC2 (16 x 73) X 100% = 9% RPS6C3 SRCC2 STATC2 TranscriptionC2 - Expected number C4 / S7: 0.09ApopRegC1 x (16 x 4) = 6 HypoxiaC1 STPC3 BH3C1 CellCycleC3 DifferentiationC1 - Observed number C4 / S7: 64Fli1C1 HistoneC1 mTORC1 SMADC1 TcellC2 TP53C1 UbiquitinC2 WntC3 2 2 > Equation: |(64 – 6)| / 6 = 560 Σ = |(Observedi – Expectedi)| / Expectedi 2 Σ = |(Oi – Ei)| / Ei Example 2: Constellation 4, signature 6

- Expected frequency C4: 107 / (16 x 73) X 100% = 9% - Expected number C4 / S6: 0.09 x (16 x 16) = 23 - Observed number C4 / S6: 0

> Equation: |(0 – 23)|2 / 23 = 23

Supplementary Fig. S6. Optimization calculation meta-galaxy pediatric ALL. Protein Expression Signature S1 S2 S3 S4 S5 S6

AdhesionC4 AdhesionC4 CellCycleC1 CellCycleC1 DifferentiationC2AdhesionC4 DifferentiationC2 CellCycleC1Fli1C5 Fli1C5 DifferentiationC2MetabolicC2 MetabolicC2 C1 PKCC3 PKCC3 SRCC3Fli1C5 SRCC3 MetabolicC2WntC1 WntC1 WntC2 WntC2 BH3C2PKCC3 BH3C2 SRCC3HeatshockC2 HeatshockC2 HypoxiaC3 HypoxiaC3 MEKC1WntC1 MEKC1 WntC2RPS6C2 RPS6C2 SMADC4 SMADC4 C2 SRCC4BH3C2 SRCC4 HeatshockC2STPC2 STPC2 UbiquitinC4 UbiquitinC4 BH3C1HypoxiaC3 BH3C1 MEKC1CellCycleC3 CellCycleC3 RPS6C2DifferentiationC1 DifferentiationC1 HypoxiaC1 HypoxiaC1 SMADC1SMADC4 SMADC1 C3 SRCC4STPC3 STPC3 TcellC2 TcellC2 UbiquitinC2STPC2 UbiquitinC2 UbiquitinC4WntC3 WntC3 AdhesionC1 AdhesionC1 ApopRegC1BH3C1 ApopRegC1 CellCycleC3AutophagyC1 AutophagyC1 CREBC1 CREBC1 CREBC2DifferentiationC1 CREBC2 HypoxiaC1CytoskeletalC2 CytoskeletalC2 Fli1C1 Fli1C1 HeatshockC3SMADC1 Protein Func,onal Group Cluster HeatshockC3 STPC3HIPPOC2 HIPPOC2 TcellC2HistoneC1 HistoneC1 C4 IAPC4 IAPC4 MAPKC1UbiquitinC2 MAPKC1 WntC3MetabolicC1 MetabolicC1 mTORC1 mTORC1 PKCC1AdhesionC1 PKCC1 ApopRegC1RPS6C3 RPS6C3 SRCC2 SRCC2 TP53C1AutophagyC1 TP53C1 CREBC1TranscriptionC2 TranscriptionC2 ApopRegC3 ApopRegC3 AutophagyC4CREBC2 AutophagyC4 CytoskeletalC2CREBC4 CREBC4 CytoskeletalC3 CytoskeletalC3 HeatshockC1Fli1C1 HeatshockC1 HeatshockC3HIPPOC3 HIPPOC3 HIPPOC2HistoneC4 HistoneC4 HypoxiaC2 HypoxiaC2 IAPC3HistoneC1 IAPC3 C5 IAPC4MAPKC4 MAPKC4 mTORC2 mTORC2 RPS6C4MAPKC1 RPS6C4 MetabolicC1SMADC3 SMADC3 STPC1 STPC1 TP53C4mTORC1 TP53C4 PKCC1TranscriptionC1 TranscriptionC1 UbiquitinC1 UbiquitinC1 AdhesionC2RPS6C3 AdhesionC2 SRCC2ApopOccurC1 ApopOccurC1 BH3C3 BH3C3 MEKC3TP53C1 MEKC3 PI3KAKTC1TranscriptionC2 PI3KAKTC1 ApopRegC3PI3KAKTC2 PI3KAKTC2 C6 PKCC2 PKCC2 STATC1AutophagyC4 STATC1 CREBC4STATC2 STATC2

Protein Constella3on TcellC1 TcellC1 AdhesionC3CytoskeletalC3 AdhesionC3 HeatshockC1ApopOccurC2 ApopOccurC2 ApopRegC2 ApopRegC2 AutophagyC2HIPPOC3 AutophagyC2 HistoneC4CREBC5 CREBC5 CytoskeletalC1 CytoskeletalC1 HeatshockC4HypoxiaC2 HeatshockC4 IAPC3HIPPOC1 HIPPOC1 IAPC2 IAPC2 MAPKC2MAPKC4 MAPKC2 MetabolicC4mTORC2 MetabolicC4 C7 RPS6C4mTORC4 mTORC4 PI3KAKTC3 PI3KAKTC3 RPS6C1SMADC3 RPS6C1 STPC1STATC3 STATC3 TP53C2 TP53C2 TranscriptionC4TP53C4 TranscriptionC4 TranscriptionC1PKCC4 PKCC4 UbiquitinC1SRCC1 SRCC1 C8 CREBC3 CREBC3 AdhesionC2DifferentiationC3 DifferentiationC3 DifferentiationC4 DifferentiationC4 mTORC3ApopOccurC1 mTORC3 BH3C3TcellC3 TcellC3 C9 TP53C3 TP53C3 TranscriptionC3MEKC3 TranscriptionC3 ApopOccurC3PI3KAKTC1 ApopOccurC3 PI3KAKTC2AutophagyC3 AutophagyC3 CellCycleC2 CellCycleC2 Fli1C2PKCC2 Fli1C2 STATC1Fli1C3 Fli1C3 Fli1C4 Fli1C4 HistoneC2STATC2 HistoneC2 TcellC1HistoneC3 HistoneC3 C10 IAPC1 IAPC1 MAPKC3AdhesionC3 MAPKC3 ApopOccurC2MEKC2 MEKC2 MetabolicC3 MetabolicC3 SMADC2ApopRegC2 SMADC2 AutophagyC2UbiquitinC3 UbiquitinC3 CREBC5WntC4 WntC4 CytoskeletalC1 HeatshockC4 HIPPOC1 IAPC2 MAPKC2 MetabolicC4 mTORC4 Supplementary Fig. S7. Meta-galaxy analysis restricted to B-ALLPI3KAKTC3 cases. To test RPS6C1 STATC3 TP53C2 whether significant new protein signatures would appear when theTranscriptionC4 analysis was PKCC4 SRCC1 restricted to B-ALL cases only, the ‘Meta-galaxy’ analysis was performedCREBC3 on B-ALL DifferentiationC3 DifferentiationC4 mTORC3 only. Each vertical patient column consists of 31 out of the 114 proteinTcellC3 clusters. Each TP53C3 TranscriptionC3 ApopOccurC3 row represents a protein cluster. Clustering enabled recognition of 10AutophagyC3 constellations CellCycleC2 Fli1C2 and 6 signatures. Blue boxes are positive for protein clusters membershipFli1C3 and yellow Fli1C4 HistoneC2 HistoneC3 boxes are negative for protein cluster membership. No significant differencesIAPC1 were MAPKC3 MEKC2 MetabolicC3 observed from the analysis performed on all samples. SMADC2 UbiquitinC3 WntC4 Supplementary Fig. S8. Significantly changed protein targets identified for each signature and each constellation. Color represent the median expression.

Signature 1

BCL2L1 BCL2L11 CASP3.cl175CASP7.cl198CASP9.cl315CASP9.cl330 CBL CCND3 CCNE2 CDKN1B CDKN1B.pS10 CDKN2A CREB1 DDX17 DUSP6

EIF2AK2.pS51 FKHRL1 GATA3 H3K27Me3 H3K4Me2 HNRNPK LCK LEF1 MAP2K1 MAPK1 MDM2 MDM4 NF2.pS518 NOTCH3 PARP1.cl214

PDK1 PDK1.pS241 PIK3CA PIM2 PTPN11 RB1 SIRT1 SMAD2 SRC.pY416 SSBP2 STMN1 TAZ TRIM24 XIAP

ASNS ATF3 BCL2 BECN1 BIRC5 CASP9 CCNB1 CD74 CDK4 CDKN1A CTNNA1 DIABLO FN1 FOXO3A GATA1

GRP78 HDAC1 ITGA2 ITGB3 JUN.pS73 KIT LGALS3 LYN MSI2 MTOR NR4A1 PRKCD.pS645 PTK2 RPS6.pS235_236 SFN

SMAD1 SMAD2.pS245SMAD2.pS465 SMAD3 SMAD5 SPI1 SQSTM1 STAT1.pY701 STK11 TAF4 TGM2 VHL

Signature 2

BAX BCL2L1 CASP3.cl175CASP7.cl198CASP9.cl330 CBL CDKN1B.pS10 CREB1 DDX17 DUSP6 FKHRL1 HNRNPK LCK MAP2K1 MAPK1

BAX BCL2L1 CASP3.cl175CASP7.cl198CASP9.cl330 CBL CDKN1B.pS10 CREB1 DDX17 DUSP6 FKHRL1 HNRNPK LCK MAP2K1 MAPK1

MAPK9 MDM2 NOTCH3 PARP1 PARP1.cl214 PDK1 PDK1.pS241 PIK3CA PIK3R1_2 PTEN RB1 SIRT1 XIAP

MAPK9 MDM2 NOTCH3 PARP1 PARP1.cl214 PDK1 PDK1.pS241 PIK3CA PIK3R1_2 PTEN RB1 SIRT1 XIAP

ATF3 BIRC5 CDK2 CDK4 CTNNA1 CTNNB1 ERN1 FOXO3A GATA1 PRKCA.pS657 GRP78 HDAC1 IGF1R ITGAL JUN.pS73

ATF3 BIRC5 CDK2 CDK4 CTNNA1 CTNNB1 ERN1 FOXO3A GATA1 PRKCA.pS657 GRP78 HDAC1 IGF1R ITGAL JUN.pS73

KIT MSI2 NR4A1 SMAD2.pS465 SQSTM1 STAT1.pY701STAT6.pY641 TAF4 VHL

KIT MSI2 NR4A1 SMAD2.pS465 SQSTM1 STAT1.pY701STAT6.pY641 TAF4 VHL

Signature 3

CASP7.cl198CDKN1B.pS10 DUSP6 LCK PIK3CA RPTOR

CASP7.cl198CDKN1B.pS10 DUSP6 LCK PIK3CA RPTOR

GATA1 JUN.pS73 KIT RB1.pS807_811 SMAD5 STAT5A_B STMN1

GATA1 JUN.pS73 KIT RB1.pS807_811 SMAD5 STAT5A_B STMN1

Signature 4

ASNS BCL2L11 CASP3.cl175CASP7.cl198CASP9.cl315 CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A DUSP6 FKHRL1 GATA3 H3K27Me3 KDR

LCK MAP2K1 MAPK1 MAPK9 NF2.pS518 PDK1 PDK1.pS241 PIK3CA PRKCA RELA RICTOR RICTOR.pT1135SRC.pY416 STAT1 STAT3.pS727

STAT5A_B.pY694 TAZ VASP XIAP

BIRC5 CDK2 CDK4 CTNNA1 CTNNB1 FOXO3A GATA1 GRP78 HDAC1 HDAC2 HDAC6 JUN.pS73 KDM1A KIT NR4A1

SMAD4 SMAD5 SQSTM1 STAT1.pY701 STAT5A_B STMN1 TAF4 TAZ.pS89 VHL WEE1 WTAP

Signature 5

BCL2L11 CASP3.cl175CASP7.cl198CASP9.cl315CASP9.cl330 CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A CREB1 DUSP6 FKHRL1 GAB2 GAB2.pY452 BCL2L11 CASP3.cl175CASP7.cl198CASP9.cl315CASP9.cl330 CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A CREB1 DUSP6 FKHRL1 GAB2 GAB2.pY452

H3K27Me3 INPPL1 LCK LEF1 MAP2K1 MAPK1 MAPK9 MDM2 NF2.pS518 NOTCH3 PARP1 PDK1 PDK1.pS241 PIK3CA PIK3R1_2 H3K27Me3 INPPL1 LCK LEF1 MAP2K1 MAPK1 MAPK9 MDM2 NF2.pS518 NOTCH3 PARP1 PDK1 PDK1.pS241 PIK3CA PIK3R1_2

PIM2 PRKCA PTK2 RELA SRC.pY416 SSBP2 STAT1 TAZ XIAP PIM2 PRKCA PTK2 RELA SRC.pY416 SSBP2 STAT1 TAZ XIAP

BIRC5 CASP3 CCNB1 CCNE1 CD74 CDK2 CDK4 CTNNA1 CTNNB1 DIABLO ELK1.pS383 FOXO3A GATA1 GRP78 H3K4Me3 BIRC5 CASP3 CCNB1 CCNE1 CD74 CDK2 CDK4 CTNNA1 CTNNB1 DIABLO ELK1.pS383 FOXO3A GATA1 GRP78 H3K4Me3

HDAC1 ITGA2 ITGAL JUN.pS73 KDM1A KIT LGALS3 LYN MAPK14 MSI2 NF2 NPM1.3542 NR4A1 ODC1 PRKCA.pS657 HDAC1 ITGA2 ITGAL JUN.pS73 KDM1A KIT LGALS3 LYN MAPK14 MSI2 NF2 NPM1.3542 NR4A1 ODC1 PRKCA.pS657

PRKCD.pS645 SPI1 SQSTM1 STAT1.pY701STAT5A_B TAF4 VHL WEE1 PRKCD.pS645 SPI1 SQSTM1 STAT1.pY701STAT5A_B TAF4 VHL WEE1 Signature 6

BAX BCL2L1 BRAF CASP3.cl175CASP7.cl198CASP9.cl315CASP9.cl330 CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A CREB1 CREB1.pS133 DUSP6 FKHRL1 BAX BCL2L1 BRAF CASP3.cl175CASP7.cl198CASP9.cl315CASP9.cl330 CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A CREB1 CREB1.pS133 DUSP6 FKHRL1

GAB2 GAB2.pY452 H3K27Me3 H3K4Me2 HNRNPK INPPL1 LCK LEF1 MAP2K1 MAPK1 MAPK9 MDM2MET.pY1230_1234_1235NF2.pS518 NOTCH3 PARP1 GAB2 GAB2.pY452 H3K27Me3 H3K4Me2 HNRNPK INPPL1 LCK LEF1 MAP2K1 MAPK1 MAPK9 MDM2MET.pY1230_1234_1235NF2.pS518 NOTCH3 PARP1

PARP1.cl214 PDK1 PDK1.pS241 PIK3CA PIK3R1_2 PIM2 PTEN PTPN11 RELA RICTOR SIRT1 SMAD3 SSBP2 TAZ VASP XIAP PARP1.cl214 PDK1 PDK1.pS241 PIK3CA PIK3R1_2 PIM2 PTEN PTPN11 RELA RICTOR SIRT1 SMAD3 SSBP2 TAZ VASP XIAP

ASNS ATF3 BIRC5 CASP3 CAV1 CCNB1 CCNE1 CDK2 CDK4 CTNNA1 CTNNB1 EGFR ERN1 FN1 FOXO3A GATA1 ASNS ATF3 BIRC5 CASP3 CAV1 CCNB1 CCNE1 CDK2 CDK4 CTNNA1 CTNNB1 EGFR ERN1 FN1 FOXO3A GATA1

GRP78 HDAC1 IGF1R ITGA2 ITGB3 JUN.pS73 KDM1A KIT LGALS3 LYN MCL1 MSI2 NR4A1 ODC1 PRKCA.pS657 SFN GRP78 HDAC1 IGF1R ITGA2 ITGB3 JUN.pS73 KDM1A KIT LGALS3 LYN MCL1 MSI2 NR4A1 ODC1 PRKCA.pS657 SFN

SMAD2.pS465 SMAD5 SQSTM1 STAT1.pY701 STAT5A_B TAF4 TGM2 VHL WEE1 SMAD2.pS465 SMAD5 SQSTM1 STAT1.pY701 STAT5A_B TAF4 TGM2 VHL WEE1

Signature 7

ASNS ATF3 BIRC2 CASP9.cl315 CCND1 CDKN1B CDKN1B.pS10 CDKN2A EGFR ERBB2 ERBB2.pY1248GAB2.pY452 HDAC3 HIF1A IGF1R ASNS ATF3 BIRC2 CASP9.cl315 CCND1 CDKN1B CDKN1B.pS10 CDKN2A EGFR ERBB2 ERBB2.pY1248GAB2.pY452 HDAC3 HIF1A IGF1R

INPP5D LCK MCL1MET.pY1230_1234_1235MSI2 NF2.pS518 NOTCH3 NRP1 PIK3CA PIM1 PIM2 PTK2 RICTOR.pT1135 RPTOR SFN INPP5D LCK MCL1MET.pY1230_1234_1235MSI2 NF2.pS518 NOTCH3 NRP1 PIK3CA PIM1 PIM2 PTK2 RICTOR.pT1135 RPTOR SFN

SMAD5.pS463 TAZ TP53.pS15 VASP XIAP YAP1 YAP1p YES1 SMAD5.pS463 TAZ TP53.pS15 VASP XIAP YAP1 YAP1p YES1

BCL2 BID CASP3 CCND3 CTNNB1 DIABLO DUSP6 EIF2AK2.pS51 EIF2S1 EIF4E GAB2 GATA1 HDAC6 JUN.pS73 KDM1A BCL2 BID CASP3 CCND3 CTNNB1 DIABLO DUSP6 EIF2AK2.pS51 EIF2S1 EIF4E GAB2 GATA1 HDAC6 JUN.pS73 KDM1A

KIT MAPK14MAPK14.pT180Y182MTOR NCL NF2 NPM1.3542 NR4A1 PRKCA.pS657 PTEN RB1.pS807_811 RPS6 RPS6.pS235_236RPS6.pS240_244 SMAD2 KIT MAPK14MAPK14.pT180Y182MTOR NCL NF2 NPM1.3542 NR4A1 PRKCA.pS657 PTEN RB1.pS807_811 RPS6 RPS6.pS235_236RPS6.pS240_244 SMAD2

SMAD4 SPI1 SSBP2 STAT1.pY701STAT3.pS727STAT3.pY705 STAT5A_B STMN1 TAF4 WTAP XPO1 SMAD4 SPI1 SSBP2 STAT1.pY701STAT3.pS727STAT3.pY705 STAT5A_B STMN1 TAF4 WTAP XPO1 Constellation 1

BCL2L11 CASP3.cl175 CASP7.cl198 CASP9.cl315 CASP9.cl330 FKHRL1 PARP1.cl214

BCL2 FOXO3A STAT1.pY701

Constellation 2

CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A DUSP6 GATA3 H3K27Me3 INPP5D LCK LEF1

MAP2K1 MAPK1 MDM2 NF2.pS518 NOTCH3 PDK1 PDK1.pS241 PIK3CA PIM2 RICTOR RICTOR.pT1135 ASNS CBL CDKN1B CDKN1B.pS10 CDKN2A GATA3 KDR MET.pY1230_1234_1235SRC.pY416 VASP

SRC.pY416 TAZ VASP XIAP

CCNE1 CDK2 CDK4 BIRC5CTNNB1 CDK4 FOXO3ACTNNA1 GATA1CTNNB1 GRP78DIABLO NR4A1KIT GATA1NCL GRP78NPM1.3542HDAC1RB1.pS807_811JUN.pS73 STMN1KIT RPS6.pS235_236TRIM24 WEE1 WTAP

Constellation 3

CBL CREB1 DDX17 EIF2AK2.pS51BCL2L11 CASP3.cl175GATA3 CASP7.cl198LCK CASP9.cl315MAP2K1 H3K27Me3MAPK1 INPP5DMDM2 LCKMDM4 MAP2K1NOTCH3 MAPK1PDK1 NF2.pS518PDK1.pS241 PIK3CA PIM2

SSBP2 STMN1 TRIM24 NOTCH3XIAP PDK1 PIK3CA RICTOR RICTOR.pT1135 RPTOR STAT1 STAT3 TAZ XIAP

BCL2 BIRC5 CASP3 DIABLO HDAC6 JUN.pS73 KDM1A NR4A1 SMAD2.pS465 SMAD4

ATF3 BECN1 BIRC5 CD74 DIABLO GATA1 GRP78 JUN.pS73 LGALS3 MTOR NR4A1 SFN SPI1 TAF4

SMAD5 SPI1 STAT1.pY701 STAT5A_B TAF4 TAZ.pS89

BCL2L1 BCL2L11 CASP3.cl175 CASP7.cl198 CASP9.cl315 CASP9.cl330 CCND3 CCNE2 CDKN1B CDKN1B.pS10 CDKN2A Constellation 4

DUSP6 FKHRL1 H3K27Me3 H3K4Me2 HNRNPK LEF1 NF2.pS518 PARP1.cl214 PTPN11 RB1 SIRT1

SMAD2 SRC.pY416 TAZ ATF3 BIRC2 EGFR HDAC3 HIF1A INPP5D MSI2 NF2.pS518 NRP1 PIK3CA RICTOR.pT1135 RPTOR SMAD5.pS463 TAZ TP53.pS15

VASP XIAP YAP1 YAP1p YES1

ASNS BCL2 CASP9 CCNB1 CDK4 CDKN1A CTNNA1 FN1 FOXO3A HDAC1 ITGA2 ITGB3

DIABLO EIF2AK2.pS51 EIF2S1 EIF4E GATA1 HDAC6 JUN.pS73 KDM1A MAPK14 MAPK14.pT180Y182 MTOR NCL NF2 NR4A1 PTEN

RPS6 RPS6.pS235_236 RPS6.pS240_244 SMAD2 SMAD4 SPI1 TAF4 WTAP XPO1

ASNS CASP9.cl315 CCND1 CDKN1B CDKN1B.pS10 CDKN2A ERBB2 ERBB2.pY1248 GAB2.pY452 LCK IGF1R

MCL1 MET.pY1230_1234_1235NOTCH3 PIM1 PIM2 PTK2 SFN Constellation 5

CASP3.cl175 CASP7.cl198 CASP9.cl315 CASP9.cl330 CCND3 CCNE2 CDKN1B CDKN1B.pS10 CDKN2A DDX17 DUSP6 FKHRL1 H3K27Me3 H3K4Me2 HNRNPK

LEF1 PARP1.cl214 RB1 SIRT1 SMAD2 SRC.pY416 TRIM24

ASNS ATF3 BECN1 CASP9 CCNB1 CD74 CDK4 CDKN1A CTNNA1 FN1 FOXO3A GRP78 HDAC1 ITGA2 ITGB3

KIT LYN PRKCD.pS645 PTK2 SMAD1 SMAD2.pS465 SMAD3 SMAD5 STK11 TGM2

Constellation 6 BCL2L1 BCL2L11 CBL CREB1 EIF2AK2.pS51 GATA3 LCK MAP2K1 MAPK1 MDM2 MDM4

NF2.pS518 NOTCH3 PDK1 PDK1.pS241 PIK3CA PIM2 PTPN11 SSBP2 STMN1 TAZ XIAP

CREB1 CREB1.pS133 FKHRL1 GAB2 GAB2.pY452 INPPL1 MAP2K1 MAPK1 MAPK9 MDM2 NF2.pS518 PDK1 PDK1.pS241 PIK3CA PIK3R1_2

PTEN RELA RICTOR TAZ XIAP

ASNS ATF3 BIRC5 EGFR FOXO3A JUN.pS73 MSI2 NR4A1 ODC1 PRKCA.pS657 SFN SQSTM1 TAF4

BAX BCL2L1 BRAF CASP3.cl175 CASP7.cl198 CASP9.cl315 CASP9.cl330 CBL CCND3 CDKN1B CDKN1B.pS10 Constellation 7 CDKN2A DUSP6 H3K27Me3 H3K4Me2 HNRNPK LCK LEF1 MET.pY1230_1234_1235NOTCH3 PARP1 PARP1.cl214

- none PIM2 PTPN11 SIRT1 SMAD3 SSBP2 VASP

CASP3 CAV1 CCNB1 CCNE1 CDK2 CDK4 CTNNA1 CTNNB1 ERN1 FN1 GATA1 Constellation 8

BRAF GATA3 DUSP6 MAP2K1 MAPK1 MAPK9 NF2.pS518 PRKCA RELA RICTOR RICTOR.pT1135 SRC.pY416 STAT1 TAZ XIAP

ATF3 BIRC5 BRCA2 DIABLO GATA1 GRP78 JUN.pS73 KIT MSI2 NR4A1 ODC1 SPI1 SQSTM1 STAT1.pY701 STAT5A_B

TAF4 TAZ.pS89

BAX BCL2L11 CASP3.cl175 CASP7.cl198 CASP9.cl315 CASP9.cl330 CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A

FKHRL1 H3K27Me3 INPP5D LCK LEF1 MDM2 NOTCH3 PARP1.cl214 PDK1 PDK1.pS241 PIK3CA

PIM2 PTK2 VASP

Constellation 9

PTPN11

KIT IGF1R LYN VHL

BAX BCL2L1 BRAF CASP3.cl175 CASP7.cl198 CASP9.cl315 CASP9.cl330 CBL CCND3 CDKN1B CDKN1B.pS10 Constellation 10

CDKN2A CREB1 DUSP6 FKHRL1 GAB2 GATA3 H3K27Me3 H3K4Me2 HNRNPK LCK LEF1

MAP2K1 MAPK1 MAPK9 MDM2 NF2.pS518 NOTCH3 PARP1 PARP1.cl214 PDK1 PDK1.pS241 PIK3CA BAX CBL CCND3 CDKN1B CDKN1B.pS10 CDKN2A FKHRL1 GATA3 H3K27Me3 H3K4Me2 INPPL1 LCK LEF1 MDM2 NOTCH3

PIM2 PRKCA RB1 RELA RICTOR SIRT1 SMAD2 SRC.pY416 SSBP2 TAZ TSC2 XIAP

PDK1 PDK1.pS241 PIK3CA PIK3R1_2 PIM2 RICTOR SMAD3 SSBP2

ATF3 BIRC5 CCNB1 CCNE1 CD74 CDK2 CDK4 CTNNA1 CTNNB1 DIABLO ERN1

CCNB1 CCNE1 CD74 CDK2 CTNNA1 CTNNB1 ERN1 FOXO3A GATA1 GRP78 H3K4Me3 HDAC1 KDM1A LGALS3 MYC FN1 FOXO3A GATA1 GRP78 H3K4Me3 HDAC1 ITGA2 ITGB3 JUN.pS73 KDM1A LGALS3

SMAD2.pS465 SMAD5 TP53 TRIM24 WEE1

BRAF CASP3.cl175 CASP7.cl198 CASP9.cl315 CASP9.cl330 CREB1 CREB1.pS133 DUSP6 GAB2.pY452 MAP2K1 MAPK1

MAPK9MET.pY1230_1234_1235NF2.pS518 PARP1 PARP1.cl214 PRKCA PTK2 PTPN11 RELA SRC.pY416 STAT1

TAZ VASP XIAP Signature

S1 S2 S3 S4 S5 S6 S7

ASNS CASP3 CASP3CASP9 CASP9CBL CDKN1A CBL CREB1.pS133 CDKN1AEIF2S1 CREB1.pS133ERN1 GAB2.pY452 EIF2S1 GATA3 ERN1HNRNPK GAB2.pY452ITGA2 ITGB3 GATA3JUN.pS73 HNRNPKKDM1A LCK ITGA2 NOTCH3 ITGB3PARP1 JUN.pS73PIK3R1_2 PTK2 KDM1A RB1 LCKSMAD3 NOTCH3SPI1 SSBP2 PARP1STAT3.pS727 PIK3R1_2STAT5A_B STMN1 PTK2 TRIM24 RB1VASP SMAD3VHL S1 S2 S3 S4 S5 S6 S7 SPI1

SSBP2 Supplementary Fig. STAT3.pS727S9. A minimal set of 30 antibodies that could predict classification of patients into signatures. Random forest selected 30 proteins that STAT5A_B were most discriminative among the signatures. Colors represent median relative expression within signatures,STMN1 ranged from the lowest (dark blue) to normal (yellow- green-cyan), to the highestTRIM24 (maroon) expression. Proteins are listed alphabetically. VASP VHL S1 S2 S3 S4 S5 S6 S7 A B

Sample ● Sample 25 TGM2 FN1 KIT FOXO3A ALL ● GATA1 NR4A1 H3K27Me3 ● SSBP2 ● SMAD1

20 10 ● IGFBP2 Cell line ● SOCS2 ● STMN1 Sample EIF2AK2 ● HDAC6 STAT5A_B CASP3 MAPK14 ● ALL patient WEE1 15 ● SMAD5 KDM1A NPM1.3542 ●● ● Cell line IGF1R ● CD74 CAV1 ● SFN ● ATF3 ●● ● HDAC1 ● ● SMAD6 10 ●● ●● BAD ● 5 ●●● ● FLI1 ● ● NCL ●● ● MDM4 ● ● ● ● ● SMAD4 ●● DDX17 ●● ● ● ● BRCA2 ● ● ● ● HDAC2 5 ● ●●● ● ● TRIM24 ● ● CCNE1 ●● CDK1 ●●● ● SPP1 ●● SMAD2.pS245 PC2 ● CREB1.pS133 SMAD3 BMI1 ● NOTCH1.cl1744 0 ● ●● PRKCA.pS657 ● CTNNB1 ● ● STAT1.pY701 CDK4 ●● JUN.pS73 0 ● ● SMAD2.pS465 ● GRP78 SQSTM1 ● ● VHL −5 ● ● PTEN ● HSPB1 BCL2 ● ● SPI1 ● RPS6.pS235_236 AKT1_2_3.pS473 ● MAPK14.pT180Y182 ● ● ● GAB2.pY452 ● PTK2 −10 ● GATA3 ● NOTCH3 ● CCND3 ● RB1 ● SIRT1 ● ● CDKN1B 5 ●●● BAX ●●●●●● ● HIST3H3 ● − ●● ●● NF2.pS518 ●●●●●● PDK1 ●●●●● PIK3CA ●● CASP9.cl315 ●● MAPK1 ● BCL2L1 ●●●●● CREB1 ● MDM2 ● ●● CASP9.cl330 ● FKHRL1 AKT1_2_3.pT308 MAPK9 MAP2K1 PDK1.pS241 DUSP6 GAB2 PARP1 MSI2 ODC1 MCL1 −10 0 10 20 CCND1 HIF1A PIM1 BIRC2 DLX1 HDAC3 STAT3 YAP1p CLPP EIF2AK2.pT451 PC1 PIM2 XIAP ERBB2 RPTOR YES1 SMAD5.pS463 RICTOR.pT1135 TAZ ITGAL LYN ITGA2 CCNB1 CDK2 BAK1 AKT1 BECN1 MTOR NF2 PARK7 PRKCD.pS645 CASP9 STK11 STAT5A_B.pY694 STAT6.pY641 STAT3.pS727 STAT3.pY705 KDR PPARG RICTOR RPS6KB1.pT389 PTPN11 RELA MTOR.pS2448 BRAF INPPL1 BID RPS6 EIF2S1 EIF4E RPS6KB1 SMAD2 TSC2 HNRNPK TNK1 SRC RPS6.pS240_244 RB1.pS807_811 TP53 TP53.pS15 LEF1 CDKN1B.pS10 SRC.pY416 PRKCA CBL LCK PARP1.cl214 CASP3.cl175 CASP7.cl198 STAT1 CDKN2A ASNS BCL2L11

Supplementary Fig. S10. (A) Unsupervised hierarchical clustering of pediatric ALL patient samples and leukemic cell lines (N=95) showed a clear separation in overall proteomic patterns between each other. Similarly, principal component analysis (B) showed a clear distinction between patient samples and cell lines.