Known Cancer Site Phosphosite Standard Deviation

Human PDX

2 Phosphosite standard deviation

0 FALSE TRUE FALSE TRUE Known cancer site

Supplementary Figure 1. Comparison of standard deviation of known cancer-related phosphosites vs. other phosphosites in human and PDX breast cancer samples. A B

C D

1.0 PDX kinase protein coefficient > 0.1 � 1.0 0.8 0.8 0.6 0.6

Sensitivity Sensitivity PDX kinase phosphoprotein coefficient > 0.1 0.4 0.4 0.2 0.2 0.0 0.0

1.0 0.8 0.6 0.4 0.2 0.0 1.0 0.8 0.6 0.4 0.2 0.0 Specificity Specificity

Supplementary Figure 2. Cis/trans pair discovery and validation. Relationship between observed sample size and significance of kinase-substrate coefficient in (A) cis and (B) trans analyses. Volcano plot showing threshold used for validation in the (C) cis and the (D) trans analyses using the PDX cohort. WNK1 T2641S2287 S183 S185 STK38L T283 STK38 T282 SRPK1 S309S311 RPS6KA5 S448 RPS6KA4 T687S721 S737 RIPK2 S393 S363S168 RAF1 S220 S43 PTK2B T842 PTK2 S910 PRKG1 T532 PRKDC S3205 PRKD1 S910 S473 PRKCD S645 T43 PRKCB S654 S660 PDGFRB S705 PASK S42 PAK4 S148 PAK2 S132S58 T169 PAK1 S144S115 T219 MARK3 S390S400T507 T564 S384

Kinase MARK2 S551S533S400 S486 S571 MAPK3 T202Y204 MAPK1 S360 MAP4K3 S661 MAP3K7 S371 IRAK1 S370 GTF2F1 T437T331S385 GSK3B T403 GSK3A S21S39 ERBB2 S1151 EIF2AK2 S340 CSNK1E T362 CHEK2 S303 CDK9 T186 CDC42BPA S1638 CASK S389 CAMK2G T287 BRAF S729 S151 ABL1 S737 1.2 1.6 2.0 2.4 Coefficient for kinase protein expression

−log10(FDR_pro_kin_plot) 2.5 5.0 7.5 10.0

Supplementary Figure 3. Potentially auto-phosphorylated cis kinase-phosphosite pairs in breast cancer with regression coefficient equal to or greater than 1. A C Cis relations tested: 630 Trans relations tested: 38,710

KinasePhospho 1576

KinaseRNA KinaseProtein 63 232 155 90 28 53 KinaseRNA 29 KinaseProtein 80 277

B ERBB2:ERBB2:S1151 D 5 15 ERBB2:ERBB2:S1083 4 ERBB2:ERBB2:S1066

10 ERBB2:ERBB2:S1054 CDK1:NUP98:S822 ERBB2:ERBB2:S1107 3 ERBB2:ERBB2:S998 CDK1:ZC3HC1:S24

PRKCB:PRKCB:T641 2 PRKCB:PRKCB:T642 CDK1:PAICS:S27 5 PRKCB:PRKCB:S660

RNA −log10(FDR) SRPK1:SRPK1:S311 RNA −log10(FDR) EGFR:EGFR:S1064 CDK1:NUCKS1:T179S181 1 PRKCB:PRKCB:T500 ABL1:MYLK:S1082 ABL1:ABI1:S231 ABL1:ABL1:T800 PRKG1:PRKG1:T532 ABL1:PRKD1:S549 ABL1:YAP1:S340 0 ABL1:ABL1:S737 WNK1:WNK1:S2287 0 MAPK11:EGFR:T693CAMK1:HDAC9:S22 PRKCQ:CCDC88A:S1674 0 10 20 30 40 0.0 2.5 5.0 7.5 PRO −log10(FDR) PRO −log10(FDR) E

7.5

5.0

2.5 PRO −log10(FDR) PRO STK38L:PRKCD:S658 STK38L:PRKCD:S664 MAPK3:GAB2:S543 MAPK3:NUP153:S645 AAK1:NUMB:T436 0.0 MAPK3:NUP153:T388 MAPK1:GAB1:S581CSNK2A1:EIF4G1:S1603MAPK3:RPS6KA3:T577 0 5 10 15 PHO −log10(FDR)

Supplementary Figure 4. Regulation of kinase-substrate pairs identified using various models. (A) Venn diagrams showing the numbers of cis-regulated phosphosites identified through quantitative association using kinase RNA or protein levels as the independent variable. (B) Comparison of significance level (-log10FDR) of cis-regulated pairs obtained through using the kinase-RNA and kinase-protein models. (C) Venn diagrams showing the numbers of trans-regulated phosphosites identified through quantitative association using kinase RNA, protein or phosphoprotein level as the independent variable. (D) Comparison of significance level (-log10FDR) of trans-regulated pairs obtained through using the kinase-RNA and kinase-Protein models. (E) Comparison of significance level (-log10FDR) of trans-regulated pairs obtained through using the kinase-protein and kinase-phosphoprotein models. A TP53BP1.S1221S1224 C GSK3B ATM MARK2.S376

2 2.5 0.0 0 −2.5

−2 TRIM28.S594S601 −5.0 MARK2.S498

2.5 2 0.0 0 −2.5 −5.0 −2 MARK2.S631 TP53BP1.S835 2.5 2 0.0 −2.5 0 −5.0 0 2 −2 −2

D SRRM1.S463S465 0 2

−2 MTOR 2.5 mutation Basal HER2−E LumA LumB Normal 0.0 B SMARCC2.S302S304 −2.5 mutation Basal HER2−E LumA LumB Normal−5.0

ATR SRRM2.S295S297 2 −7.5 2.5 0 0.0 −2 −2.5 −4 −5.0 −6 SMARCC2.S302 −7.5 SRRM2.S1064 2 2.5 0 0.0 −2 −2.5 −4 −5.0 −7.5

−6 FARSA.S301 0 2 −2 2 E 0 RPS6KB1 CAD.S1859 −2 mutation2.5 Basal HER2−E LumA LumB Normal −4 0.0 −6 −2.5 0 2 −4 −2 −5.0 −7.5 EIF4ENIF1.S951 2.5 mutation Basal HER2−E LumA LumB Normal 0.0 −2.5 −5.0 −7.5 2.5 URI1.S372 0.0 −2.5 −5.0 −7.5 0 2 4 −6 −4 −2

mutation Basal HER2−E LumA LumB Normal

Supplementary Figure 5. Top trans-regulated phosphosites of (A) ATM (B) ATR, (C) GSK3B, (D) MTOR, and (E) RPS6KB1. A B 1.0 1.0

0.5 0.5

0.0 0.0 Correlation coefficient Correlation coefficient

−0.5 −0.5

0 5 10 15 20 25 4 6 8 10 Linear distance (aa) 3D distance (ångström)

Supplementary Figure 6. Correlation between (A) linear and (B) 3D distances and correlations of phosphosite pairs on the same PDB structure. 1.2 A S737 ifelse(sig, "black", "grey") black grey T800 0.8 Y412 Size/20 2 4 S637 T871 0.4 −log(FDR) S936 8 Regression coefficient 6 S702 S824S827 4 S588 0.0 S828 2 S16

0 250 500 750 ABL1 phosphosite position

1.00 B S910 ifelse(sig, "black", "grey")

T20 S568 black Y570 grey 0.75

Size/20 T24 2 0.50 S390 4 T13 S708 S843 0.25 −log(FDR) 6 Regression coefficient

4 0.00

S840 2

Y576 −0.25 0 250 500 750 PTK2 phosphosite position

C S309 ifelse(sig, "black", "grey") 0.6 black grey T337

S610 0.4 −log(FDR)

1.5 S320

1.0

0.2 S320S330 S330 0.5 Regression coefficient

0.0 Size/20 2

S416 4

0 200 400 600 RIPK1 phosphosite position

Supplementary Figure 7. Landscape of cis-regulation of phosphosites in (A) ABL1 (B) PTK2 and (C) RIPK1. Basal EBV+ lymphoproliferation LumB Positive CLDN low HER2−E Negative

HER2.Status PR.Status ER.Status PAM50

EMD:S123 ABL1 WHIM2 WHIM4 WHIM6 WHIM8 WHIM9 WHIM13 WHIM14 WHIM21 WHIM25 WHIM30 WHIM12 WHIM17 WHIM46 WHIM11 WHIM35 WHIM47 WHIM16 WHIM18 WHIM20 WHIM24 WHIM26 WHIM27 WHIM37 WHIM43 AKT1:S126S129 AKT1

MAP3K5:S1033 AKT2

ZYX:T306 ARAF

MAP2K2:S295 BRAF BRAF:S364

PLCG1:S1222 EGFR

ERBB2:S1151 ERBB2

STAT3:S727 Level JAK2 3 STAT1:S727 2

TSC2:S923 1 PITPNM1:S1237 MAPK1 0 NCOA6:S1481 −1 −2 GJA1:S255 MAPK14 −3 IRS1:S270 GORASP2:T222 MAPK3 value CTTN:S405 FALSE

SRRM1:S463S465 MTOR TRUE MTOR:S1261

VCP:S7 PRKDC PRKDC:S2672

RAF1:S43 RAF1

RBM10:S788 RAPGEF1:S332 SRC CFL1:S24

SYK:S297 SYK PLCG1:S1234 WHIM2 WHIM4 WHIM6 WHIM8 WHIM9 WHIM13 WHIM14 WHIM21 WHIM25 WHIM30 WHIM12 WHIM17 WHIM46 WHIM11 WHIM35 WHIM47 WHIM16 WHIM18 WHIM20 WHIM24 WHIM26 WHIM27 WHIM37 WHIM43

Supplementary Figure 8. Heatmap of regulated kinase-substrate pairs where the kinase or the substrate is a potential druggable target in 24 breast cancer PDX. The sample-pair showing outlier pair event is outlined. Only the top 3 regulated pairs were shown for each kinase when there were more than 3 pairs showing kinase-substrate outliers. Basal EBV+ lymphoproliferation LumB Positive CLDN low HER2−E Negative

HER2.Status PR.Status ER.Status PAM50 WHIM2 WHIM4 WHIM6 WHIM8 WHIM9 WHIM13 WHIM14 WHIM21 WHIM25 WHIM30 WHIM12 WHIM17 WHIM46 WHIM11 WHIM35 WHIM47 WHIM16 WHIM18 WHIM20 WHIM24 WHIM26 WHIM27 WHIM37 WHIM43

CNV RNA Protein AKT1 AKT1:AKT1:S126S129

CNV Protein AKT2 AKT2:MAP3K5:S1033

Mutation CNV BTK RNA CNV CCND1 CNV Protein CDK4

CNV RNA Protein ERBB2 ERBB2:ERBB2:S1151

Mutation CNV ESR1 CNV HDAC2 CNV HSP90AA1 CNV Protein HSP90B1

CNV Protein IDH1 CNV IGF1R Mutation CNV JAK2:STAT3:S727 JAK2 JAK2:STAT1:S727

CNV RNA MAPK1:TSC2:S923 MAPK1 MAPK1:PITPNM1:S1237 MAPK1:NCOA6:S1481

CNV RNA MAPK14 MAPK14:GJA1:S255

CNV MAPK3:CTTN:S405 MAPK3:GORASP2:T222 MAPK3 MAPK3:IRS1:S270

CNV RNA MDM2

Mutation CNV Protein MTOR MTOR:SRRM1:S463S465 MTOR:MTOR:S1261

Mutation CNV RNA PIK3CA Protein

CNV SRC:CFL1:S24 SRC:RAPGEF1:S332 SRC SRC:RBM10:S788

CNV SYK:PLCG1:S1234 SYK SYK:SYK:S297 Supplementary Figure 9. Druggability analysis of single and paired events in 24 breast cancer PDX samples. Druggable eventsdata2 identifiedCNV in the mutation,Kinase−substrate CNV, RNA, pair proteinMutation and phospho-pairProtein level forRNA breast cancer PDX samples. CNV RNA Protein AKT1 AKT1:GSK3A:S278 AKT1:AKT1:S126S129 CNV RNA ARAF Protein CNV RNA Protein BRAF BRAF:MAP2K2:S295 BRAF:BRAF:S364 CNV Protein CCND1 Mutation CNV RNA Protein EGFR EGFR:GAB1:S547 EGFR:PLCG1:S1222 EGFR:PTK2:S910 CNV RNA Mutation Protein AKT1 AKT1:GSK3A:S278CNV AKT1:AKT1:S126S129RNA ERBB2 Protein ERBB2:ERBB2:S1151 CNV RNA ARAF Mutation Protein CNV RNA CNV GNAS Protein RNA Protein BRAF BRAF:MAP2K2:S295Mutation BRAF:BRAF:S364CNV RNA HDAC8 Protein CNV Protein CCND1 Mutation CNV Mutation RNA CNV IGF1R Protein RNA IGF1R:IGF1R:S1365 Protein EGFR EGFR:GAB1:S547 EGFR:PLCG1:S1222Mutation EGFR:PTK2:S910RNA Protein MAP2K4 MAP2K4:MAP2K4:S394 Mutation CNV RNA ERBB2 Mutation Protein MAP3K1 ERBB2:ERBB2:S1151RNA CNV RNA Mutation MAPK14:FOXO3:S413 CNV MAPK14GNAS MAPK14:MAPK1:Y187 RNA Basal HER2−E LumB Positive MAPK14:GJA1:S255 Protein Mutation Mutation Equivocal LumA Negative CNV CNV HDAC8 Protein RNA MAPK3:MKNK1:S39 Protein MAPK3 MAPK3:PALLD:S55 MAPK3:IL16:S584HER2.statusMutation PR.statusCNV RNA IGF1R Mutation ER.statusProtein CNV pam50 PIK3CA IGF1R:IGF1R:S1365Protein Mutation Mutation CNV RNA MAP2K4 RNA Protein PIK3CB MAP2K4:MAP2K4:S394Protein Mutation CNV RNA MAP3K1

RNA A7.A13F.01A C8.A12T.01A A8.A079.01A E2.A154.01A E2.A158.01A A8.A076.01A A2.A0YF.01A C8.A12V.01A AO.A0JJ.01A A8.A06Z.01A A2.A0T3.01A A2.A0T6.01A A8.A08Z.01A C8.A130.01A C8.A135.01A C8.A138.01A C8.A12L.01A C8.A131.01A C8.A134.01A D8.A142.01A A7.A0CJ.01A A2.A0EY.01A A2.A0EV.01A AO.A12F.01A E2.A15A.01A C8.A12Z.01A AO.A0J9.01A AO.A0J6.01A AO.A0JL.01A AR.A0TT.01A A8.A06N.01A A2.A0D2.01A AN.A0AJ.01A AR.A1AV.01A AO.A126.01A BH.A0AV.01A AR.A0TV.01A C8.A12U.01A A2.A0EX.01A A8.A09G.01A A2.A0SX.01A AN.A0FL.01A AO.A0JE.01A BH.A0BV.01A BH.A0E1.01A BH.A0E9.01A A2.A0YC.01A A2.A0YD.01A AN.A04A.01A A7.A0CE.01A AN.A0AL.01A AO.A0JC.01A AO.A12B.01A AO.A12E.01A AN.A0FK.01A BH.A0C7.01A BH.A18U.01A BH.A0C1.01A BH.A18N.01A A2.A0YG.01A AR.A0TX.01A AR.A0U4.01A A2.A0EQ.01A AO.A12D.01A AR.A0TR.01A AR.A1AP.01A AR.A1AS.01A BH.A18Q.01A A2.A0YM.01A AO.A03O.01A AO.A0JM.01A A2.A0SW.01A A2.A0CM.01A BH.A0DD.01A AR.A1AW.01A AN.A0AM.01A Protein BH.A0DG.01A RAF1:BAD:S75 CNV RAF1 RAF1:MTA1:S449 RNA RAF1:RAF1:S43MAPK14:FOXO3:S413 MAPK14 MAPK14:MAPK1:Y187 MAPK14:GJA1:S255CNV RNA RARA Protein Mutation CNV Protein MAPK3:MKNK1:S39CNV MAPK3 MAPK3:PALLD:S55RNA TOP2A MAPK3:IL16:S584Protein Mutation CNV PIK3CA Protein Mutation data2 CNV Kinase−substrate pair Mutation Protein RNA CNV RNA PIK3CB Protein CNV RNA Protein RAF1:BAD:S75 RAF1 RAF1:MTA1:S449 RAF1:RAF1:S43 CNV RNA RARA Protein CNV RNA TOP2A Protein

data2 CNV Kinase−substrate pair Mutation Protein RNA

Supplementary Figure 10. Druggable events identified in the mutation, CNV, RNA, protein and phospho-pair level showing members of the MAP kinase cascades. subtype self first_neighbor second_neighbor Normal LumB LumA Basal mutation 3 2 2 1 1 subtypeself first_neighbor second_neighbor subtype self first_neighbor second_neighbor subtype self first_neighbor second_neighbor 1 0 0 0 −1 −1 −1 −2 −2 Normal −2 −3 −3 −3 LumB level LumA as.numeric(value) as.numeric(value) as.numeric(value) Basal Subtype PIN1:S42 KRT8:S74 IRS1:S629 NPM1:Y67 NPM1:S70 KRT8:T431 KRT8:S425 MTA1:S562 MTA1:S522 RSF1:S397 PRC1:T470 Normal PRC1:S571 PRC1:S513 ORC2:T226 WEE1:T190 BRCA2:S93 ORC2:S280 NPM1:S254 CLIP1:S180 KIF2A:S624 IRS1:S1132 WEE1:S137 MCM2:S108 CEP55:S436 PLK1 protein GTSE1:S480 RBM17:S169 Normal XRCC1:S226 PRKCD:T295 PRKCD:S658 ESPL1:S1126 BUB1B:T1042 TOP2A:S1391 TOP2A:S1377 TOP2A:S1213 MAP2K1:T286 TRIOBP:S1955 TP53BP1:S776 TP53BP1:S403 TSC22D4:S165 RACGAP1:T579 RACGAP1:T342 TP53BP1:S1647 TP53BP1:S1623 TP53BP1:S1553 TP53BP1:S1033 HSF1:S363S368 EIF4ENIF1:S564 PPP1R13L:S357 XRCC1:S199S226

PLK1 phosphoprotein

mutation gene LumB LumB 3 2 1 LumA LumA 0 −1 −2 HER2−E −3 HER2−E Basal Basal as.numeric(value) Subtype Subtype VIM:T20 VIM:S25 mutation NF2:S12 SSH1:S897 MAPT:T498 OCLN:S340 mutation NF2:S518 PXN:Y118 SSH1:S1042 ABI2:S301 PRKD2:S710 PRKD2:S203 PRKD2:S197 PRKCE:T710 PRKCE:S368 PRKCE:S346 PAK1:S144 MTA1:S449 Subtype CTTN:S418 CTTN:S405 STAT3:S727 STAT1:S727 LIMK1:S298 PRKCE protein JAK2 protein JAK2 PIN1:S42 IQGAP1:S1540 SPEN:T1140 RICTOR:S1344 KRT8:S74 RPS6KB2:S416 PGAM1:S118 NPM1:Y67 NPM1:S70 IRS1:S629 KRT8:T431 KRT8:S425 MTA1:S562 MTA1:S522 RSF1:S397 PRC1:T470 PRC1:S571 PRC1:S513 ORC2:T226 WEE1:T190 BRCA2:S93 ORC2:S280 NPM1:S254 CLIP1:S180 KIF2A:S624 IRS1:S1132 WEE1:S137 MCM2:S108 PLK1 protein CEP55:S436 GTSE1:S480 RBM17:S169 XRCC1:S226 PRKCD:T295 PRKCD:S658 ARHGDIA:S101 GIT1:S592S596 ESPL1:S1126 BUB1B:T1042 TOP2A:S1391 TOP2A:S1377 TOP2A:S1213 MAP2K1:T286 TRIOBP:S1955 TP53BP1:S776 TP53BP1:S403 TSC22D4:S165 RACGAP1:T579 RACGAP1:T342 TP53BP1:S1647 TP53BP1:S1623 TP53BP1:S1553 TP53BP1:S1033 HSF1:S363S368 EIF4ENIF1:S564 PPP1R13L:S357 MORC2:S677S681 RICTOR:T1175S1177 XRCC1:S199S226 SPEN:S1268S1278

MAPT:S512S515S516

PRKCE phosphoprotein JAK2 phosphoprotein JAK2

PLK1 phosphoprotein gene gene gene each of the kinase. each of Supplementary Figure 11. Druggable kinase-substrate cascades originating from (A) JAK2 (B) PRKCE and (C) and (B) PRKCE (A) JAK2 from cascades originating 11. Druggable kinase-substrate Figure Supplementary of level phosphoprotein by the ordered were heatmap in the The samples samples. cancer in the 77 breast PLK1 C B A S846

CDK14 EIF4G3 NUAK1 EIF2AK4 T824 MARS TLK2 S166 ASF1A CDKL5 S395 PBX2 MAP4K2 S299 HLCS RIPK1 S1080 DAB2IP MAP2K7 S20 EXOSC5 FER S207 NSF S445 PPP1R12A

S1131 NIPBL S717 Y901

CAMK1 S500 HDAC5 S2658 S451 Y901 S66

S22 PDPK1 HDAC9 ROCK2

CCNY

S528 PIK3CG S954

S1010

S83 NEK2

S780

S1499

T848T866 SRRM2 S50 EEF1D S2426

S832

CDK16 S1064

AKT1S1 S295S297 S738

S2398 S605S607 AMOTL2 S223 UBR4 SET BAG6 S87 MARK3 S2132 T220 PPP1R2 S294 SAFB2S1747

MTOR S1857 S973 T22 S463S465 S194 S367 T983S994 VCPIP1 NCAPG OXSR1 S177S179 SRRM1 RANGAP1 DUT PKN2 HUWE1 S260 S875 GMPS ICK CDC25C MAP4K5 ZC3HC1 ILK S573 DTL S2694 PATL1S463 CHD4 S276 TP53 MAP7 HIST1H1E S1012

S438 HMGA1 T614S616 TPR NUMB S964S973 KAT5 S952S954 S2917 T73S87 S1103 S964 DLGAP5 SCML2 S1112 CCDC6 T436 S1318 S1370 CKAP2 SMARCC2 T2034 SUPT5H S1101S1103 TCOF1 S307 S3752 CRK S436 S2067S2071 POU2F1 S194 AAK1 S2071 T495 S460 T357 S7 S428 CAMKK2 PPP2R5D S2044 S2527 S3757 NOLC1 S954 S302S304S306 S2535 S238 S120 S1236 NUP98 LARP1 T1231S1233 S1084 S2619 S1444 USP28 S367 SPTBN1 PI4KB T848 HIRIP3 S3816 S513 S1153 ACIN1 S1041 S283SP1 S3564 T1425 T478 S2365 MAP4 S493S499 T799 S351S352 S1053S1623 T927 S315 CUX1 S381 S59 S302 SUN2 PALLD S671 T49 ILF3 S195 MDC1 S973S975 S341S345 S402T404 XIAP S885 S998 S442 UBR5 T1817 S2241S1431 S1467 STMN1 S302S304 T239 S815 S503 S24T28 STIM1 Y720 S302 T318 STK10 RPA2 S804 S458 S792 S302S304S306 S302S304 S183HMGN3S211S263 ATM T1677 T492T496 S471 S24XRCC6 S24 S402 S490T42 S29 ANKRD17S428 PDLIM5 S315 S767 VCP DOK1 USP10 T514 T277 S420LMNB2 T18 T18 S1467S1486 S116 CNOT2 S591 S347 S102T84 S375 NUFIP2 S313 T84S87 T322 S671S683 S1185S108 S1185 MYLK T492 RUNX1 S291 S223S232 T1287S359 S835 S503 AKT1 S408 S1484 S200 T515 IKBKE ZCCHC8 HNRNPUL1S240 S618 S453 S495 S78 S618S591 S52 S748 S598 S736 MAPK6 PTPN12 NOC2L S157 S1043 S240 S357 T1034 S534T231T233S776 S523 S257 S123 S153 S153 S358 S523 TERF2 S624 S280 T1567 S505 S710 T492T496 UIMC1 S677 DAXX S194 T607T610 T661 S697 KMT2D S1221S1224 S822 TP53BP1S822 ATR S510 S583 S89 NUP153 S31 SMARCA4 FLNA T492 S266 S49 S345CDK9 S489 S165 S906 PLK3 S1459 S493 GPS1 S49S56 S56 S696 S2128 HSF1 S242 S242 SETDB1 S112 T927 S917PDS5BS1373 S7 S598 YWHAE NCOA2 S270 S308 S278 S328 S917 CAMKK1 S1082 S47 T592 S301 S576 S583 S571 S46 S407 BAZ2A S257 S2101S520T34S37 T455 S658 S257 S1083 S835 T571 S19 S477 S2615 S835 S2 S541S504 CDK12 S2199 S1623 GORASP2 S1369 S227 S652 T859 XRCC4 CDK7 S579 S3530 S1082S2695 PTEN S129 T492T496S500 S276 SMARCAL1 S512T199 S242 S278S282 S46 S340 S189 T914 S11 S2941 S365 S4 S439 S112 ZC3H18 S45 T496 S65 FARSA LIG1 S126S129 S718 T1989 S4822 S1647 S835 S385 S251 S327S328 S1081 T255 T199 SRPK2 S2327 RCHY1 S771 TOPBP1 HES1 S1358T1370 S1066 S1373 CDK11B S227 S3019 S332 CBL S1051 FGFR3 PRKACA T415 PHF14 S1882 S505 S46 S258 S1763S1764 SRA1 KMT2AS819 S179 S52 S110 S1084 NPM1S1875 PRKDC S499 S274S276 T249 YWHAH S576 S888 S1139 BOD1L1 S2372 S1861 NDRG1 S77 S1647 PAICS YWHAZ EIF3F CREB1 S70 S2905 S27 S88 T2467 T1870 S1683 S1906 T328 S87 S446 MCM4 S1868 S403 S1789S1800 S2284 S1861 S326 T3581 S323 MSN S40 T1255 BRD4 CDK2S788 AKT2 GSK3A CDK1 T25 S139 S1623 T1880S201 RPS6KA2 SIK1 S347 S304 S363S368 S1535S88 S1033 S464 S114 S1531 ORC1 CIC S330 S776S1830S1849 TGFBR2 S136 DMPK S471S1100 S333 S2526 S1047 T2153 S38 PTPN2 S209 S52 AKAP13 S504 T25 S397 S596S598S601 T522 S288 S1033 RET S1100S1101 SUPT6H S1868 S534 S1821 FAM110A T606 S403 CDK13 S303S307 S40 PLECS594S601 Y67 S215 PIK3R4 S209 S11 ZMYM3 S1896 ETS1 S576 T14Y15 S473 S2510 S259S1800 S1553 S1862 S742 S422 S259 S257 S70 S1910 EIF2S1 S527 T168S10 T925 S1033 S601 S126 S925 S415 S887 RPL12 RSF1 S1429 T495S257 S400S403 S105 S1896 S52 S55 S189 S254 S605 S498 S527S531 S108 MAP4K1 T369 CCM2 T60 S128 S1849T1854 NEDD1 SOS1 S52S55 S52 S270 T394 S241 TRIOBP S52S55 S259 S16S25 S306 S1833 S55 S259 CAMSAP1 T179S181POLR2A S438 S46 Y279 T237 BRAF TGFB1I1 S147 S1373T1381 T369 KAT7 S576 CEP55 S670 S447 S1553S46 S1850 S1690S1691 S98 T189 S823 S1831 S886 S301 S25 S2849PHB2 S86 S547S549 S391 S464 BRCA2 S48 S71 MAP3K8 S344 S259 T826 S1389 S86 S647 T2613 S397 ANKLE2 T388 S13 S143 S180 S1955 NUMA1 SCYL2 S505 S393 S1862 S2672 MAP3K5 S110 S645 S418 S645 S436 T1149 NCBP1 T394 T1042 SLC9A1 T1228 S645 S391S393 NELFA S157 S226 S93 S620 T373 S461S485 KIF11 S76 S293 POLDIP3 ESPL1 S796T799 CARD11 S644 S110 T470 T892 AKAP12 S1126 S28 S28 S946 TSC2 T222 T286 T323 T388 S7 T172 T100 S1105 S976 S42 VIPAS39 S1341S1342 S21 T222 S23 S295 PIN1 S1134S1137 ANXA2 S547S549 S385 PLK1 S1577 S445 S261 BTK DYRK1B T579 CEBPB S739 MCM2 S1435 S886 T1240 S447 S226 UNG T1412 S1213 S296 S624 RACGAP1 S958 S714 T20 T1042 S240 S547 S547 S207 T286 S571 S1373T1381 S457 RPS6KB1 S283 STK25 S629 RPS6 S259 S344 S36 S216 S216 S703 RPS6KA3 S421 S260S282 S368 S12S22 S154 EYA3 NUCKS1 S85 PDCD4 S527 S281 S160 KIF2A S480 S1254 S605 T25 T226 VASP S645 S330S338S219 RPS3 S13 S51 S3207SLAIN2 S342 S330S338 PRKCQ S280 S207 T592 S25 S209 T342 T2055 NUP50 S739 S207 S498 S282S285 CCT2 S28S34 PRC1MARCKS BUB1B S207S739 S693 S113S98 MAP2K1 S1389 S605 S164 S1341S766S263 S372 T282 S467S470S471 S390 GATAD2A T1149 S946 S426 S1859 S373 S1132 S513 S496 S1373T1381 S946 T1027 T1231 S357 T190 S1391 PRRC2A LMO7 T335 S188 S497S498 S13S415S419EIF4B ZYX T358 S137 S12S183 KIF23 TSC22D3 MAPK12 S92 T1027 S288 S288 S313 S1400 T210 S1341 S645 S67 S527S531 MAP2K2 S259S267 S1376 S498 S576 S563 T498 PTK2B T38 S22 GTSE1 S123 S1389 S938 ANKS1A PLCG2 S2172S2176 RANBP2 S626 S742 T498 ORC2 T19 RPS6KA1 S597 S323 TMPOS98 NUP214 T1149 S1254 S232 S1134 CLK3 S2184 T1175S1177S159 URI1 S330 S1966 S1213 S2606 S867 T714 S496 S10 Y185 CAD S344 S58 S273 S278S282 S282 PARN S1100S1101S425 S1388 EIF2AK2 T1919 S196 S1204 S151 S923 DSP S47 RIF1 S703 S1341 MKNK1 S307 S168 S923 T52 XRCC1 S2161 IREB2 S386 S647 S2160 S283 S782 S1377S137 RANBP3 S1341 S636 S647 IRS1 T401S405T411 RB1 S74 S190 S462 S73 T306 S307 AURKB Y187 PFKFB3 T1042 S462 S110 T577 MAP2K6 S418 S557 T530 S21 IRAK3CYLD S560 S404 T323 S453T455 SH2B1 STUB1 T577 T292 S261 S513 BLM S221 T184 S99 KRT18 T431 SF3B1 S489 S108 T190 IKBKB S629S636S498 S136 S449 S166 S307 MKL1 S221 T18 T292 CTTN S311 S270 S22 OPTN S188 S359 T306 S267 S446 GAPVD1 S6 S432 S218 S263 S449 S222 RBM17 S412 S1023 GAPDH S386 RICTOR S53 S1163 S672 T421S424 S459 S951 LMNB1 S489 S446TRIM28 S522 S333S1023 RNPS1 S422S11 S504 S47 S419 S180 NCOR1 S389S75 S272 T235 S436 TOP1 S263 CLK1 S535 DEK S359 S78 S282 THOC5 S199S226 S205 S412 S205 NCOR2 S39 S270 MAPKAPK2S143 S449 S55 S39 S241 S28 S307 S283 S281 S214 S537 MAX S386 T430 S96 S236 S645 KSR1 S166 TOP2A S222 S1985S511 S405 S141 S143 WWTR1 MAP3K14 S96 S358T364 S28 S489 DNMT1 ARAF S226 MEF2A S511 TRIM24 S221 T401S405 S98 S505 S155 S303 S151 STK24S169 T295 S501 S366 NFKB2 ADAM17 Y187 S681 S259 S828S576 MYBBP1A ERCC3 S636 S7 S107S418T306 TRIM29T328 S471 S213S217 T222 KRT8 T270 S73 S25 S629S636S4 S288 HNRNPK S785 LSP1 S269 S169 S645 GPBP1 S116 T257S266 SIRT2 TERF2IP S785 S382 S345T141 S488 S658 TTK PTPRC S658 S139 AHNAK S226 T323 T14Y15 S113 S210 S508 S382 T430 S126 T185 S210 T620 MAPK3 S217 PDIA6 S62 S862 S11 S449 T257 PDE4D S126 S664 S210 S219 S110 S862 S705 GTF2I S241 S506S213 TRIP10T201S206 S426 S552 CSNK2B MAPK1 S562S197S134 ADRBK1 RTN4 PDGFRB SAMHD1 CHEK2 T401S405 S56 T14 LIN52 S114 ABI2 HNRNPC S382 T184 S9S21 TP53BP2MAP3K7 S78S82 S46 S369 S99 T401S405T411 S220 T401 S96 BAD S639 T182 S103 S28 S576 LMNA S1483 T453 S2815S2825 S766 FOXK2 S821 S311 EIF5 CDCA8 S359 S183S187 S581 S518 S206 HDAC7 S425 CLASP2 S67 S558 S118 S9 S73 S29 YWHABT233 S1313 S291 S522 WEE1DYRK1A DDX3X S36 S320S321 T182 S246 T1175S1177 UBAP2L S480 S1001 S558 S259S264 S376 LUZP1 S405 S36 MAPKAPK5S405 S47 S636 S564 MTA1S683 MKI67 USP1 NCL T199 S114 S75 Y187T1135 S587 S418 NCKAP5LRAD23B VTN S1344 S330 S297 IRAK4 T185 S194S395 NUP35MLLT4 S339 S354 S1143 S745 S449 RIPK3 S506 S213 S596S598S601S307 S449 T180Y182 EIF4ENIF1S1374 STK38 S527S530 BMPR1B S177 S311 T641 S103 PTPN3 S946 S156 S77 ITGB4S47 S1302 T76 S543 CTNNA1 S345 T283 S574 HDAC4 S212 EP300 S268 S446 S280 S304 S543 NFATC4 NCF2S113 S562 MAST2 AATF S311 S1101 S279 S873 S694T700 S110S113 S270S489 S131 T185Y187 T222 RAF1 T548 S458 TPD52 S73 S506 IRF3 S394 T1215 THRAP3 NCOA1 S844 S966S159 STK36 S658 T185Y187 S87 S564 CLIP1 S73 S661S663 S217 S139T585 S426 Y427 EIF3J S410 S9 S302Y313 S905 S301 S165BUB1 S410 T334 S862 S183S187 S694T700 S432 T498 S639 MBP S320 T185 T87 S382 S113 ARID3A T121 S480 S197 PRKCD S212 WNK1 S455 NEK3S241 S65 S645 NEK6 S139 S658 S113 S346 S512S515S516 S176 S584 S217 S379S605 S639 S213S217 Y185 TFAP2AS9S21 T180 AKAP11 S175 S526 S449 S664 S288S296 PSEN1 CC2D1A S576 Y187 T185Y187 S15 S110S113 S530 T69T71 S302 T183Y185 S357 PRKCI S316 S266 S445 T219 S217 S441 SUFU S82 S30 S576 PML S1111 S10 S427 S90 ERG S395 S115 S584 S4 S425 S727 T185 S119 S386 S1318 S2256 T183Y185 T182 T182 NASP S339 S2S11 S215T219S425S1237 S90 S110 T183 T308 S562 CAMK2D S844 S65 S501S1481 T185PECAM1 EIF2S2 T41S44 S401 S112T116 T185 S664Y185 S422S433 S98S108 S112T116T41S44 S13 S62 S43 PSPC1S345 S345 S513 S13 RPA1 S480 S686 T295 S300 BCL2L11 S720 S73 S213S217 S345 S287 GAB2 RPS6KA5S622S626 S15 S84 S38 S975 NCF1 NMT1 GPBP1L1S100S103S304 S374METTL3S503 S160 S139 RPS6KB2 S449 RBM4 T488 S129 ATXN3 S120T123 S409 TSC22D4 S123 S165T173 T23 TRIP6S185 CLK2 S138 S966 T201S206 T295 S639 T23 S213 JAK2 S98 S206 HIPK2 S10 S517 GSK3B S446 S120T123 PKN1 S10 S752 TCF3 S717 S641 S187S519 S505 S491 S653 S62 S505STK38L T197RPS6KA4 S480 CSDE1 S408 S112 S418 S86 S294 S187 S745 CDKN1B MLX S364 S300 S408 S348 S83 T687 S694T700 MAPT MATR3 LIMA1S177 S359 T357 S164 S386 T1030S257 S259 HIPK1 S424 RAP1GAP S851 HCLS1 S78 S951 S133S721 S199 T110T119 S158 S664 S9 T769 S284 AGAP2 T226 S195S733 S100S110S113 T199 S658 OTUD7B S721 S379 S127 T295 S90 T3S21 S84 S1001 S560 S46 S693 S112T116 S84 PBK S726 HSPB8 S808 S782 S62 S731 S300 S212 S579 SRPK1 S223 S260S261 SORBS3 ATF1S110 S727S395 PPP1R13L S62 S234S238 SP100 T180Y182 S493 S68 S565 S65 MAPK14 MAPK9 S58 S332 MAP2 S705 FYN MAPK8 STK3 XPO1 S110 S2 PRKAR1A S106 S258 S532 DLG1 S376 S204 RASSF1S717T720 T596 S77S83 NEK9 S68 VIM S55 S300 T693 S97 S112T116 SFPQ S90 S673 S199 S256 S413S354 S62T69T71S600 T69T71 S526 SYK T693 S425 S280 PELP1 GPSM2 S18 S207 S634 S638 S727 S427 Y118 NDEL1 S526 S449 S120T123 ATXN2L S28 S207 T117 T467 S220 S7 T1616T1619 BCL6 S46 S103 S20 T110T119 S102 S199S201 S315S320 TBC1D10B S46 T180 S82 CNKSR1 LCP2S1238 S416 S103 S885 S531 PARD3 S568S572 S1099 S713 S419 Y118 S568 S195 ADD2 S62 S100 T714S727 T43 S1084 S547 ATF2 S230 S885 T183 T245 S1555 S83 S581 FOXO3PITPNM1 S483 S648 STAT1 FOXO1 STK17A ADD1 IL16 S657S661 S1084 NCOA6 T357 S227 S411S437 S21 S106 S592 T69T71 S727 S68S727 S102 T385 SRSF1 S264 T245 S1238 DUSP16S126S130 S710 S90 S416 T498 T33 S412 T180 T23 T23 S701 S366 S268 S597 LYN S12 EIF4EBP1 MAP2K3 S205 TNS3 S675S681 JUND T208 S135 Y185 PPP2R5C S512S515S516 S187 CSNK1DS552 T954 S795 S572 S408 KHDRBS1S332S498 S596S600 NEK7T344 S414 T3S21 T436 S5 S298 HSPB1 S29 S359 S68 S292 S508 GRK6 FYB S255 S276 EIF4H S300 T119 MAPK13 T32 PRKACBPEAK1S29 S513 S144 S285S290 CD5 S306 T526 RAN S131 S631 S226 S203 CSNK2A1 S179 S120T123 S641 T20 S1250 KRT19 MAP3K6 Y185 STAT3 T632S531S298 S340 CSNK1E S376 S102 S680 S100 OCLN S395 T257S268 S293 S586 RXRA S73 S73 T51T53 YAP1 S325 S962 DAPP1 S258 T51 STK4 S391 APBB1 S97T101 S432 S25 S260 T62 T93T95 S113 S268 S35S40 S675S681 T693 T62 S627 S354 S409 S762 S208 S1042 S420 T245 S1234 T230 S311 S258 S260S261 S110 S430 S715 S103 S340 S414 MEF2C Y118 PRKAA2 MITF S40 S552 PER2 S567 ERFS2449 S35 RUNX2 VHL T143 S366 STAP2 S210 S65 S419S420 SHC1 S731 S144 LIMK1 ROCK1 S221 NFATC1 MORC2 S648 GJA1 PRKCE S2283 S4523 S240 S289BAIAP2S908 S179 T184 PRKX T290 S792 MAP2K5 S155

Y221 T710S68 S677S681 S1540 S2724S298 S496 SRC S1603 T800 PRKAA1 BCLAF1 S4520 S366 S49 MAPK7 S1268S1278 BLVRA S230 S142 S289 S843 S263 S908 LRP1 S1221 S84 S366 PRKCA S731T733 S342 PTK2IQGAP1 PAK1 S268 T208S720 T500 S1166 TBK1 ARHGEF6 S910 T1438 S143 T1140 MARK2 S118 S1379 ATF7 S244S44T51T53 T532 T693 Y118S197 S1222 S68 S784 S282 EGFR JUN S366 S264 S788 S684 CTNNB1 MAPK11 S1355 S613 PLCG1 PRKCB SPEN KIF13B S885 PGAM1 S665S681 T24 SH3PXD2BS579 S3 T59 S824S827 S728 S555 S547 S203 RELA S755 S4 S287 UTRN S449 S84 S692S696 PXN T98 T494 SQSTM1 S106 S197 S367 PRKG1 S710 S332 S692 S549 APC S172 S332 T90 T800 S102 S709 ARHGEF2S1915 S208 S548 GAB1 S303 EIF4G1 EPB41 S828 S374 LATS1 FAM129B S863 RBM10 S687 CALD1 T62 S307 S99 S710 S304 T62 PPP2R5A ERBB2 PDE5A S24 S518 T494 S101 S492T494 S721 VCL CTNND1 S1290 S42 T208 S12 PIP5K1C S1713 NEK1 S2283 BCAR1 S445 S305 S1142 T869 S153 S592S596 S163 S226 LASP1 S120 FHOD1 S675S681 S731S735 RAPGEF1 S255 PRKD1 S30 S255S261 S24 S936 S571 ABL2 S391 T62 S429S430 PRKD2 ABL1 S252 ERCC6 S23 S73 S735 AFAP1 Y118 S146 S202 T93T95 ATG9A CSNK1A1

S1084 S272 RPTOR T245 S249 ARHGDIA FIP1L1 S897 S1042 S910 PRKCZ S1042 S123 PRKG2 NF2 S218 Y412

S237 S1264 CSNK2A2 S761 NEIL2 S1039 S721 CASP7 GIT1 MYH9 S12 S863 S68

S37 SIK3 S536 EMD S920 S518 SSH1 STK11 HSP90AB1

S305 PAK2 S120S153 PRKD3 ULK1 S468 CFL1

MARK1

ZRANB2 S23

CDC37 S24

LIMK2

BCR

T485

FES

VRK1 T2T3S4 BANF1 STK39 T980 SLC12A7 SMARCE1 BAG2 FBXW5 FHL1 PSMA7 SMYD2 GRIK2 USP37 SMAD9 MFN1 RASGRF1 HDAC3 ATF6 GEM CUL5 STMN3 ASCC3 ELF3 PPP1R14C MLH1 TFCP2 MCL1 VPS72 TRIM21 TUFM CSTF2T BMF GTF2A1 BCL2 AK2 CREM ABCA1 UBXN1 STAM2 GINS2 MAP4K3 TBCE DDX58 POLL HDAC6 STRAP CCND1 FMR1 SNIP1 BARD1 RPS27L FBXO4 THOC1 ACACB ELMO1 GMEB1 SUMO3

MSX2 CLDN3 TGM2 IRF5 RNH1 MYBL1 MAP3K10 ATP2B4 USF2 ATP2A2 TP53RK DTNB ALYREF TXN NEFH DENND3 ULK2 CDKN1C MBNL1 NMI CDC16 CDK11A DNM2 SPAG5 CRMP1 PYCR1 MAP9 SNUPN APP LARP6 SSR1 LUC7L2 PCBD1 PTPN22 GNB2L1 YWHAG PRDX5 REM1 RAB4A PEA15 BCAM CCDC86 HBP1 KDM3A HSPB6 RAB11A SLC12A5 DAPK3 RDX MEN1 DIABLO AKIRIN2 U2AF1 STARD10 EIF2AK3 PSEN2

ASCC1 RGCC ECT2 GPX1 NRIP2 PHGDH APLP2 TPM1 CDC27 ZBED1 CBFA2T3 GSN NOB1 PLEK SPR PRPF8 HEXIM1 BECN1 USP16 AP2M1 COIL EEF1A1 FANCD2 PACSIN1 DHX38 REV3L SCYL3 RND3 SP3 NOXA1 TCF7L2 LRWD1 EXOSC7 FUS VAV3 GSTP1 CCDC82 FHL2 EIF6 PPP1R1B RIN1 PYGB LMTK2 GATA3 CASP6 HIST1H1C SH2D4A MPZL1 ADD3 PKN3 H2AFX BAZ1B GTF2F1 RMDN3 SMAD3 PPM1B

ZAK KIF22 SOX9 CDK2AP1 CNTROB RAD50 ATG13 IGFBP3 IFI16 METTL1 WRN SOD1 RPL11 SNW1 EDC3 RPL21 RSBN1 USP4 RGS14 CBLB FADD PFKFB2 PSME3 SORT1 PKMYT1 RAB3IP SNRNP70 SPHK2 MPHOSPH10 RMI1 G6PD NCOA4 STON1 SH3RF1 USF1 CBX4 F11R ITGB1 PLD1 CAMK1D LRP6 ZSCAN18 AGO2 RAB5B SDCBP TRAF2 DOCK6 RARG NCKIPSD FLI1 MRTO4 PRPF3 UTP3 UHRF1 PHF17 ITGA4

SNAPIN MATK TRIM16 AHR RAP1A IKZF1 LAMTOR5 IMPDH2 SMARCD3 ITPR1 ACAP1 QKI GNA12 PCNT MAP2K4 NCALD ZNF148 JPH2 TFRC ZC3H4 POLD3 KMT2E GDI2 WNK2 COL17A1 JUNB BMP2K ERAL1 HABP4 RRAD MYL9 TPT1 SH3GL1 KIF4A TBL1XR1 PPIE CAMK2B FOXO4 CTBP1 FOXC1 BRD9 NFKBIA APOE CTPS1 IKBKG CDCA2 BABAM1 GFPT1 DNAJB2 MTMR2 WIPF1 ZMYM2 PPP1R1A BRD2 RAB14 RAB11FIP2

STAT5B WWOX TNK2 LCP1 PIK3C2A CELF1 BBC3 MCM7 DEPTOR CDC20 WASF2 CCDC80 DDA1 KLC1 ZBTB4 NDC80 DVL2 PIK3CA SIRT6 HNRNPH2 ZFP36L1 ATXN1 NFAT5 CRIP2 TGS1 MLKL YY1 R3HDM2 FEN1 MDM4 ZNF768 TFE3 UGDH CAV1 RCC1 PARP1 PPP1R12C MAPKAP1 BLNK CAPN2 PPP2CA SIAH2 ROBO1 SLC12A6 WNK4 LRRK2 RNF4 CDC23 CANX PAK6 SLBP PAG1 EFHD2 TAOK3 SND1 TFAM

UPF1 SMG1 SMAD4 NLK CREBBP EDF1 CBX1 ZCCHC11 CENPF MICALL1 PDE4C ISCU MTSS1 EIF2S3 RARA TTC3 GIGYF2 DPF2 PPP1R14A ITCH HTT LDHA MUC1 MARK4 AIMP1 CENPJ PLK4 PGR EIF4A3 SNAP23 PLA2G4A VAV2 ANAPC4 EEF2 TIAM1 CDT1 ARPC1B RPLP2 CD79A NDE1 PBRM1 PPP1R8 MYH10 ACO1 TYK2 SMARCAD1 NRBP2 CASP3 RTKN CEP250 RAPGEF2 CEBPD PRDM10 RIPK2 USP14 CAT

CCNL2 LAS1L TARDBP ARID1A TFPT MYC BUB3 GTF3C3 DAPK2 SMC1A TRIM26 E2F4 DES FH ELF4 FRK KLF3 DAP ULK3 EXOC7 SAV1 MAPK8IP3 SUB1 SNRK UBE2I DNAJC5 HSPA9 POGZ NEK4 PYGO2 ATP5C1 EML3 SNX17 CALU NUP107 ANKRD28 EIF2B5 GPRC5A ABCF1 SRSF2 TRIO JUP DNM1L PRDX1 IQGAP2 TLK1 SERBP1 TSNAX RBL2 RCAN1 STIP1 PYCR2 IRS2 NR3C1 CRKL LATS2

SPEG PFN1 MPLKIP FLNC PARP10 TAGLN2 RELB ZNF692 HNRNPU GRIN2A IGF1R KALRN PLEKHG2 RPS27 SIK2 SSRP1 MKNK2 TAB1 CHGB CDK18 PGM1 PSMA6 HDLBP RBBP8 TOR1AIP1 HMGN5 HN1L RIOK2 PA2G4 BRSK1 BRSK2 PIK3R1 NUDC PTPRA IRAK1 CAMK2G MAZ PKM PRDM1 EIF2AK1 YWHAQ DMTN DPYSL2 RBM27 PDGFRA CAMK4 DSTN PRKCH HIST1H4A RBBP5 SPDL1 TPX2 ACACA NCBP2 SUPT16H GRB7

STIL CROCC DLC1 CHAF1B SUZ12 COBLL1 KATNA1 DYRK2 JDP2 PTPN1 AR AKAP8 ASF1B RPRD1B OGT CSRP1 PDCD5 COL4A3BP SLC4A1 SLC9A3R1 CARHSP1 FAM168B TDP1 TBC1D1 PHLPP1 CDCA5 BRCA1 S100A11 PDE3A SF3B2 TBX3 BMPR2 ARFIP1 EZH2 JAK3 DSN1 PEBP1 MAD1L1 PTPN11 DAB2 ITGB2 KIF20B MAP3K1 HIRA PLD2 DIAPH1 ZFP36 KIT KHSRP FGFR1OP LRCH3 WAS ELK1 PRPF4B NOL7 VRK3

NACA YBX1 PTPN6 HCK NAP1L1 TK1 ARAP1 PTK6 HMGN1 PTPN7 MKI67IP HNRNPH1 NBN EZR SYNJ2 KDM2A RRN3 NOS3 PIKFYVE TOPORS ZNF609 DBNL ARHGAP5 TCF4 DCK RRM2 MAP3K11 ZCRB1 PAK4 MAP4K4 GPI ANXA1 RBM12 SLC12A2 CCNE1 NDRG2 ARHGAP21 CDH1 UBE2O NRBP1 XRCC5 TAF7 TAF1 RAD18 GIT2 ELAVL1 TANC1 NFKB1 PAWR DLG4 STAT6 SVIL CHD7 ZEB2 DIAPH3 SFN

CGGBP1 RBL1 TNKS1BP1 LIPE HNRNPD EPS15 MACF1 GSG2 CYBA ERCC6L AMPH SLC9A3R2 PPP1R12B GORASP1 PLG CAV2 ETV6 LZTS1 TACSTD2 SOX10 KDM1A MAF1 PIP5K1B ATRIP PRKAB1 KLC2 CASP9 STAT5A DCLK1 HMGCS1 DLG2 BCL3 RCSD1 NUP62 TESK2 NFATC3 ESR1 SRF ABI1 PIK3C3 GPKOW TBC1D22A HSP90AA1 SMAD2 ENO1 DCLK2 RALBP1 CD44 PRKAR2B GLI3 ZHX1 SMC3 SPN NCOA3 TOP2B CNN2

SIRT1 GYS1 SPAG7 RAD9A MCM3 MED1 DAPK1 LRRFIP1 PIAS1 ZC3H11A AKT3 SUMO1 BAG3 HNRNPA1 ARHGAP24 TSC1 PTGES3 USP7

Supplementary Figure 12. Landscape of cis and trans-regulations identified in the breast cancer cohort. For each node of the network diagrams, the color represents the relative level of basal compared to luminal A/B breast cancers, where blue indicates higher level in luminal and red indicates higher level in basal tumors. For the edg- es, the darkness of the color is scaled by the degree of correlation coefficient and the width is scaled by -log(FDR) of the association. Supplementary Figure 13. Response curves for three EGFR peptides. For peptide IPLENLQIIR, varying concentrations of heavy peptide (0, 20, 50, 100, 200, 800 and 1600 amol/μL) and a constant concentration of light peptide (125 amol/μL) were spiked into a tryptic digest of a human breast cancer xenograft tissue (0.1 µg peptide) and 5 μL of sample at each data point was analyzed by LC-SRM. Its limit of detection (LOD) and low- er limit of quantification (LLOQ) were both determined at 20 amol/μL level. For the two phosphopeptides NGLQSCPIKED(pS)FLQR and ELVEPL(pT)PSGEAPNQALLR, varying concentrations of heavy peptide (0, 0.4, 0.8, 1.6, 3.125, 6.25, 12.5, 25, 50, 100, and 200 fmol/μL) and a constant concentration of light peptide (200 fmol/ μL) were spiked into the same breast tumor xenograft sample (100 µg peptide), followed by IMAC enrichment of the phosphopeptides and LC-SRM analysis. The LOD and LLOQ for both phosphopeptides were 0.4 fmol/ μL and 1.6 fmol/μL, respectively. The LOD was determined by S/N>3, and the LLOQ was determined by both S/ N>10 and CV<20%. Supplementary Figure 14. Inter-day experiment for three EGFR peptides. For peptide IPLENLQIIR, 20, 100 and 400 amol/μL concentrations and a constant amount of light peptide (125 amol/μL) were spiked into a tryptic digest of a human breast cancer xenograft tissue (0.1 µg peptide) and 5 μL of sample at each data point was analyzed by LC-SRM. The inter-day CVs for all three measured concentrations ranged from 1.4% to 14%. For the two phosphopeptides NGLQSCPIKED(pS)FLQR and ELVEPL(pT)PSGEAPNQALLR, 3.125, 6.25 and 12.5 fmol/ μL and a constant amount of light peptide (200 fmol/μL) were spiked into the same breast tumor xenograft sample (100 µg peptide), followed by IMAC enrichment of the phosphopeptides and LC-SRM analysis. The inter-day CVs for all three measured concentrations ranged from 1.2% to 24% and 0.5% to 13% for NGLQSCPIKED(pS) FLQR and ELVEPL(pT)PSGEAPNQALLR, respectively.