REACTOME_EGFR_DOWNREGULATION REACTOME_CYTOSOLIC_TRNA_AMINOACYLATION REACTOME_DEPOLARIZATION_OF_THE_PRESYNAPTIC_TERMINAL_TRIGGERS_THE_OPENING_OF_CALCIUM_CHANNELS KEGG_TASTE_TRANSDUCTION REACTOME_PLATELET_DEGRANULATION -log(Q-value) KEGG_MTOR_SIGNALING_PATHWAY REACTOME_DOWN_STREAM_SIGNAL_TRANSDUCTION REACTOME_SIGNALING_IN_IMMUNE_SYSTEM REACTOME_E2F_TRANSCRIPTIONAL_TARGETS_AT_G1_S REACTOME_DEADENYLATION_OF_MRNA REACTOME_SYNTHESIS_OF_GPI_ANCHORED_PROTEINS KEGG_AMINOACYL_TRNA_BIOSYNTHESIS 12 KEGG_NON_SMALL_CELL_LUNG_CANCER REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES KEGG_TGF_BETA_SIGNALING_PATHWAY REACTOME_REGULATION_OF_INSULIN_SECRETION KEGG_NICOTINATE_AND_NICOTINAMIDE_METABOLISM KEGG_AMYOTROPHIC_LATERAL_SCLEROSIS_ALS BIOCARTA_MET_PATHWAY REACTOME_E2F_MEDIATED_REGULATION_OF_DNA_REPLICATION REACTOME_MRNA_PROCESSING KEGG_CHEMOKINE_SIGNALING_PATHWAY REACTOME_PEROXISOMAL_LIPID_METABOLISM 10 REACTOME_PYRIMIDINE_METABOLISM BIOCARTA_ACTINY_PATHWAY REACTOME_COPI_MEDIATED_TRANSPORT BIOCARTA_CBL_PATHWAY REACTOME_MITOCHONDRIAL_FATTY_ACID_BETA_OXIDATION REACTOME_STEROID_METABOLISM KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS KEGG_GLUTATHIONE_METABOLISM REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS BIOCARTA_CHEMICAL_PATHWAY KEGG_GLYCOSYLPHOSPHATIDYLINOSITOL_GPI_ANCHOR_BIOSYNTHESIS KEGG_COLORECTAL_CANCER KEGG_PARKINSONS_DISEASE 8 BIOCARTA_BLYMPHOCYTE_PATHWAY ST_STAT3_PATHWAY REACTOME_GLUCOSE_REGULATION_OF_INSULIN_SECRETION ST_G_ALPHA_I_PATHWAY BIOCARTA_SPRY_PATHWAY REACTOME_MEMBRANE_TRAFFICKING BIOCARTA_NDKDYNAMIN_PATHWAY KEGG_ALPHA_LINOLENIC_ACID_METABOLISM REACTOME_REV_MEDIATED_NUCLEAR_EXPORT_OF_HIV1_RNA KEGG_PANCREATIC_CANCER KEGG_ERBB_SIGNALING_PATHWAY REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS 6 REACTOME_SIGNAL_AMPLIFICATION KEGG_VEGF_SIGNALING_PATHWAY KEGG_TIGHT_JUNCTION KEGG_LONG_TERM_DEPRESSION REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS REACTOME_HIV_LIFE_CYCLE REACTOME_NEP_NS2_INTERACTS_WITH_THE_CELLULAR_EXPORT_MACHINERY BIOCARTA_BAD_PATHWAY REACTOME_ACTIVATION_OF_THE_PRE_REPLICATIVE_COMPLEX REACTOME_TRNA_AMINOACYLATION REACTOME_PHASE_1_FUNCTIONALIZATION_OF_COMPOUNDS REACTOME_NUCLEAR_RECEPTOR_TRANSCRIPTION_PATHWAY 4 REACTOME_SIGNALING_BY_EGFR KEGG_PPAR_SIGNALING_PATHWAY BIOCARTA_UCALPAIN_PATHWAY REACTOME_MITOCHONDRIAL_TRNA_AMINOACYLATION REACTOME_NA_CL_DEPENDENT_NEUROTRANSMITTER_TRANSPORTERS BIOCARTA_ETS_PATHWAY KEGG_ALANINE_ASPARTATE_AND_GLUTAMATE_METABOLISM KEGG_ETHER_LIPID_METABOLISM KEGG_WNT_SIGNALING_PATHWAY KEGG_PROPANOATE_METABOLISM KEGG_FRUCTOSE_AND_MANNOSE_METABOLISM KEGG_DNA_REPLICATION REACTOME_TRANSPORT_OF_MATURE_MRNA_DERIVED_FROM_AN_INTRON_CONTAINING_TRANSCRIPT 2 REACTOME_ELECTRON_TRANSPORT_CHAIN BIOCARTA_TGFB_PATHWAY REACTOME_UNFOLDED_PROTEIN_RESPONSE REACTOME_LAGGING_STRAND_SYNTHESIS KEGG_SMALL_CELL_LUNG_CANCER KEGG_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS REACTOME_MITOTIC_PROMETAPHASE REACTOME_SIGNALING_BY_ROBO_RECEPTOR REACTOME_GLUCONEOGENESIS REACTOME_OPIOID_SIGNALLING 0 REACTOME_MICRORNA_BIOGENESIS BIOCARTA_MCM_PATHWAY KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS BIOCARTA_LAIR_PATHWAY REACTOME_ACTIVATED_AMPK_STIMULATES_FATTY_ACID_OXIDATION_IN_MUSCLE REACTOME_ENERGY_DEPENDENT_REGULATION_OF_MTOR_BY_LKB1_AMPK KEGG_ECM_RECEPTOR_INTERACTION REACTOME_CELL_JUNCTION_ORGANIZATION REACTOME_GLUCOSE_AND_OTHER_SUGAR_SLC_TRANSPORTERS REACTOME_DNA_STRAND_ELONGATION KEGG_ENDOCYTOSIS REACTOME_TRANSPORT_OF_THE_SLBP_INDEPENDENT_MATURE_MRNA BIOCARTA_MEF2D_PATHWAY KEGG_PROGESTERONE_MEDIATED_OOCYTE_MATURATION ST_T_CELL_SIGNAL_TRANSDUCTION KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION REACTOME_VPR_MEDIATED_NUCLEAR_IMPORT_OF_PICS REACTOME_GLYCOGEN_BREAKDOWN_GLYCOGENOLYSIS REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS KEGG_RIBOFLAVIN_METABOLISM BIOCARTA_P53_PATHWAY REACTOME_REGULATION_OF_INSULIN_LIKE_GROWTH_FACTOR_ACTIVITY_BY_INSULIN_LIKE_GROWTH_FACTOR_BINDING_PROTEINS SA_FAS_SIGNALING REACTOME_CLASS_B2_SECRETIN_FAMILY_RECEPTORS REACTOME_TELOMERE_MAINTENANCE KEGG_ADHERENS_JUNCTION REACTOME_CELL_CELL_ADHESION_SYSTEMS REACTOME_TRANSPORT_OF_RIBONUCLEOPROTEINS_INTO_THE_HOST_NUCLEUS REACTOME_MTOR_SIGNALLING REACTOME_NCAM1_INTERACTIONS KEGG_B_CELL_RECEPTOR_SIGNALING_PATHWAY REACTOME_PLATELET_ACTIVATION_TRIGGERS KEGG_N_GLYCAN_BIOSYNTHESIS BIOCARTA_RARRXR_PATHWAY REACTOME_APCDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B BIOCARTA_LONGEVITY_PATHWAY BIOCARTA_IL3_PATHWAY REACTOME_GRB2_SOS_PROVIDES_LINKAGE_TO_MAPK_SIGNALING_FOR_INTERGRINS_ BIOCARTA_HSP27_PATHWAY KEGG_RNA_POLYMERASE REACTOME_NUCLEAR_IMPORT_OF_REV_PROTEIN KEGG_TRYPTOPHAN_METABOLISM REACTOME_G2_M_CHECKPOINTS KEGG_AXON_GUIDANCE REACTOME_REGULATION_OF_AMPK_ACTIVITY_VIA_LKB1 REACTOME_CLATHRIN_DERIVED_VESICLE_BUDDING REACTOME_PHOSPHORYLATION_OF_THE_APC REACTOME_ACTIVATION_OF_RAC REACTOME_CONVERSION_FROM_APC_CDC20_TO_APC_CDH1_IN_LATE_ANAPHASE KEGG_HUNTINGTONS_DISEASE KEGG_CHRONIC_MYELOID_LEUKEMIA KEGG_PYRUVATE_METABOLISM KEGG_T_CELL_RECEPTOR_SIGNALING_PATHWAY REACTOME_LATE_PHASE_OF_HIV_LIFE_CYCLE KEGG_SNARE_INTERACTIONS_IN_VESICULAR_TRANSPORT KEGG_BUTANOATE_METABOLISM REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL REACTOME_METABLISM_OF_NUCLEOTIDES KEGG_ARACHIDONIC_ACID_METABOLISM REACTOME_BIOLOGICAL_OXIDATIONS REACTOME_SYNTHESIS_OF_GLYCOSYLPHOSPHATIDYLINOSITOL KEGG_OOCYTE_MEIOSIS KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION REACTOME_CYTOCHROME_P450_ARRANGED_BY_SUBSTRATE_TYPE KEGG_P53_SIGNALING_PATHWAY REACTOME_SIGNALING_BY_PDGF REACTOME_CLASS_A1_RHODOPSIN_LIKE_RECEPTORS REACTOME_INACTIVATION_OF_APC_VIA_DIRECT_INHIBITION_OF_THE_APCOMPLEX KEGG_FATTY_ACID_METABOLISM REACTOME_FORMATION_OF_PLATELET_PLUG REACTOME_PLATELET_ACTIVATION REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH REACTOME_VITAMIN_B5_(PANTOTHENATE)_METABOLISM KEGG_PYRIMIDINE_METABOLISM KEGG_OXIDATIVE_PHOSPHORYLATION KEGG_INSULIN_SIGNALING_PATHWAY REACTOME_SLC_MEDIATED_TRANSMEMBRANE_TRANSPORT REACTOME_INORGANIC_CATION_ANION_SLC_TRANSPORTERS KEGG_OTHER_GLYCAN_DEGRADATION KEGG_FOCAL_ADHESION REACTOME_TRANSCRIPTION KEGG_PURINE_METABOLISM REACTOME_GPCR_LIGAND_BINDING REACTOME_INTEGRATION_OF_ENERGY_METABOLISM REACTOME_G_ALPHA_S_SIGNALLING_EVENTS KEGG_CELL_CYCLE REACTOME_HEMOSTASIS REACTOME_REGULATION_OF_LIPID_METABOLISM_BY_PEROXISOME_PROLIFERATOR_ACTIVATED_RECEPTOR_ALPHA REACTOME_GLUCOSE_METABOLISM REACTOME_TRANSLATION_INITIATION_COMPLEX_FORMATION REACTOME_METABOLISM_OF_CARBOHYDRATES KEGG_APOPTOSIS KEGG_PEROXISOME REACTOME_FORMATION_OF_THE_TERNARY_COMPLEX_AND_SUBSEQUENTLY_THE_43S_COMPLEX KEGG_REGULATION_OF_ACTIN_CYTOSKELETON KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY KEGG_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM KEGG_RENIN_ANGIOTENSIN_SYSTEM KEGG_LYSOSOME REACTOME_JNK_PHOSPHORYLATION_AND_ACTIVATION_MEDIATED_BY_ACTIVATED_HUMAN_TAK1 REACTOME_ACTIVATED_TAK1_MEDIATES_P38_MAPK_ACTIVATION KEGG_O_GLYCAN_BIOSYNTHESIS REACTOME_RNA_POLYMERASE_I_III_AND_MITOCHONDRIAL_TRANSCRIPTION REACTOME_TRANSMEMBRANE_TRANSPORT_OF_SMALL_MOLECULES REACTOME_FORMATION_AND_MATURATION_OF_MRNA_TRANSCRIPT REACTOME_SNRNP_ASSEMBLY REACTOME_METABOLISM_OF_RNA KEGG_PANTOTHENATE_AND_COA_BIOSYNTHESIS KEGG_PATHWAYS_IN_CANCER KEGG_JAK_STAT_SIGNALING_PATHWAY REACTOME_MRNA_SPLICING_MINOR_PATHWAY REACTOME_DOWNSTREAM_EVENTS_IN_GPCR_SIGNALING REACTOME_ELONGATION_AND_PROCESSING_OF_CAPPED_TRANSCRIPTS REACTOME_AXON_GUIDANCE REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION REACTOME_MRNA_SPLICING BIOCARTA_PROTEASOME_PATHWAY KEGG_SPLICEOSOME REACTOME_METABOLISM_OF_AMINO_ACIDS REACTOME_CELL_CYCLE_CHECKPOINTS REACTOME_G1_S_TRANSITION REACTOME_INFLUENZA_VIRAL_RNA_TRANSCRIPTION_AND_REPLICATION KEGG_RIBOSOME REACTOME_GTP_HYDROLYSIS_AND_JOINING_OF_THE_60S_RIBOSOMAL_SUBUNIT REACTOME_ORC1_REMOVAL_FROM_CHROMATIN REACTOME_S_PHASE REACTOME_PEPTIDE_CHAIN_ELONGATION REACTOME_VIRAL_MRNA_TRANSLATION REACTOME_HOST_INTERACTIONS_OF_HIV_FACTORS REACTOME_SYNTHESIS_OF_DNA REACTOME_CYCLIN_E_ASSOCIATED_EVENTS_DURING_G1_S_TRANSITION_ REACTOME_REGULATION_OF_APC_ACTIVATORS_BETWEEN_G1_S_AND_EARLY_ANAPHASE REACTOME_FORMATION_OF_A_POOL_OF_FREE_40S_SUBUNITS REACTOME_CDT1_ASSOCIATION_WITH_THE_CDC6_ORC_ORIGIN_COMPLEX REACTOME_SCF_BETA_TRCP_MEDIATED_DEGRADATION_OF_EMI1 REACTOME_MITOTIC_M_M_G1_PHASES REACTOME_DNA_REPLICATION_PRE_INITIATION REACTOME_SIGNALING_BY_WNT REACTOME_AUTODEGRADATION_OF_CDH1_BY_CDH1_APC REACTOME_M_G1_TRANSITION REACTOME_P53_INDEPENDENT_DNA_DAMAGE_RESPONSE KEGG_PROTEASOME REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21 REACTOME_VIF_MEDIATED_DEGRADATION_OF_APOBEC3G REACTOME_REGULATION_OF_ORNITHINE_DECARBOXYLASE REACTOME_CDC20_PHOSPHO_APC_MEDIATED_DEGRADATION_OF_CYCLIN_A REACTOME_STABILIZATION_OF_P53 REACTOME_TRANSLATION REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT REACTOME_DIABETES_PATHWAYS REACTOME_GENE_EXPRESSION REACTOME_INSULIN_SYNTHESIS_AND_SECRETION REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_BETA_CELLS REACTOME_METABOLISM_OF_PROTEINS REACTOME_HIV_INFECTION REACTOME_CELL_CYCLE_MITOTIC REACTOME_APOPTOSIS REACTOME_INFLUENZA_LIFE_CYCLE Fast/ Slow Continuous Supplemental Figure 1A primary metabolic process cellular metabolic process metabolic process macromolecule metabolic process cellular process biological regulation regulation of biological process regulation of cellular process negative regulation of protein ubiquitination negative regulation of ligase activity cellular macromolecule metabolic process regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle negative regulation of ubiquitin-protein ligase activity regulation of ubiquitin-protein ligase activity positive regulation of ligase activity positive regulation of protein ubiquitination positive regulation of ubiquitin-protein ligase activity proteasomal protein catabolic process RNA processing regulation of protein ubiquitination regulation of cellular macromolecule biosynthetic process protein metabolic process regulation of biosynthetic process RNA metabolic process ubiquitin-dependent protein catabolic process regulation of cellular biosynthetic process regulation of macromolecule biosynthetic process positive regulation of cellular protein metabolic process negative regulation of protein modification process positive regulation of protein metabolic process regulation of gene expression nucleic acid metabolic process response to stimulus developmental process positive regulation of molecular function negative regulation of cellular protein metabolic process positive regulation of catalytic activity positive regulation of cellular process cellular biosynthetic process establishment of localization in cell cellular macromolecule biosynthetic process negative regulation of biological process multi-organism process cellular component organization small molecule metabolic process regulation of nitrogen compound metabolic process cellular macromolecule catabolic process negative regulation of cellular process regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process cellular component organization or biogenesis at cellular level positive regulation of protein modification process proteolysis involved in cellular protein catabolic process biosynthetic process modification-dependent macromolecule catabolic process macromolecule biosynthetic process positive regulation of metabolic process positive regulation of macromolecule metabolic process modification-dependent protein catabolic process regulation of RNA metabolic process macromolecule catabolic process cellular component organization or biogenesis positive regulation of cellular metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process nucleobase, nucleoside, nucleotide and nucleic acid metabolic process catabolic process transport nitrogen compound metabolic process regulation of ligase activity establishment of localization regulation of metabolic process cellular catabolic process proteasomal ubiquitin-dependent protein catabolic process cellular nitrogen compound metabolic process regulation of primary metabolic process multicellular organismal process positive regulation of biological process cellular developmental process response to organic substance small molecule catabolic process anion transport inorganic anion transport ion transport cellular component biogenesis response to external stimulus ncRNA metabolic process ribonucleoprotein complex subunit organization response to stress anatomical structure morphogenesis ncRNA processing ribonucleoprotein complex assembly vesicle-mediated transport response to hormone stimulus negative regulation of cellular metabolic process negative regulation of metabolic process organic acid metabolic process carboxylic acid catabolic process nucleobase, nucleoside and nucleotide metabolic process nucleoside phosphate metabolic process regulation of cell death negative regulation of macromolecule metabolic process oxoacid metabolic process regulation of programmed cell death carboxylic acid metabolic process cellular protein metabolic process proteolysis monocarboxylic acid metabolic process response to endogenous stimulus cellular component organization at cellular level cellular component biogenesis at cellular level response to chemical stimulus negative regulation of protein metabolic process cell cycle process mRNA metabolic process anatomical structure formation involved in morphogenesis regulation of protein modification process regulation of cell communication regulation of signaling cellular polysaccharide metabolic process carbohydrate metabolic process regulation of signal transduction regulation of tooth mineralization regulation of phosphorylation antigen processing and presentation of exogenous peptide antigen cellular localization segmentation regulation of protein phosphorylation regulation of response to stimulus cellular response to stimulus cellular carbohydrate metabolic process antigen processing and presentation of peptide or polysaccharide antigen via MHC class II antigen processing and presentation of peptide antigen via MHC class II regulation of odontogenesis tissue development regulation of phosphorus metabolic process localization regulation of phosphate metabolic process anterior/posterior pattern formation polysaccharide metabolic process antigen processing and presentation of exogenous antigen protein localization regulation of fibroblast proliferation regulation of kinase activity Fast/ Slow Continuous Supplemental Figure 1B ** ** ** ** ** ** ** ** ** ** ** **
** ** MD MD ** 0.4 0.6 0.8 1.0 1.2 0.4 0.6 0.8 1.0 1.2
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** P P 0.4 0.6 0.8 1.0 1.2 0.4 0.6 0.8 1.0 1.2 ** **
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0.4 0.6 0.8 1.0 1.2 ** 0.4 0.6 0.8 1.0 1.2
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Da P f Da P f Supplemental Figure 2 B) A) SHARP
Fast HCC1187 Mean # Cell Lines With Gene/Class Overlap 5 Slow
Continuous atCniuu Slow Continuous Fast
Fast OVCAR5
Slow
Continuous Supplemental Figure 3 Random General Essentials
Fast HP
Slow
Continuous 205 genes 134 genes n = 125 n = 54
ALG10B ISG20 RPL31 ATXN7 NID2 ATP6V0D1 LCN10 RPL32 n = 80 BPTF NUPL1 AURKB LSM3 RPRD1A BDKRB1 LSM6 RPS12 C14orf166 OIP5 BMPR1A LY96 RPS14 BUB1B MCM2 RPS18 COPS6 OPA1 CCNB3 MPL RPS19 ANAPC4 PRPF3 RPS25 COPS8 PDZK1IP1 CCT6A MYO3B RPS3 AQR PRPF31 RPS27A CDC40 NACAP1 RPTOR CSE1L PSMA2 CDK11B NCBP1 RTF1 ARCN1 PSMA1 RPS29 CENPO NCOR2 SCRG1 CDC5L PSMA3 RPS3A CYP27C1 PSMB6 CHEK1 NEDD8 SF3A2 CHD4 PSMA6 RPS6 DDX21 PTPRC CLTC NR1D1 SF3B1 DYNC1H1 PSMB2 RPS7 COPA NUDT21 SF3B2 DDX51 RBMX COPS2 NUDT4 SF3B5 EEF2 PSMB3 RPS8 COPZ1 NUP205 SHFM1 EFTUD2 PSMC3 RPS9 DLC1 REXO2 DDR1 NXF1 SMARCC1 EIF2S2 PSMC4 RPSA EGFLAM ROD1 DDX18 OR51E1 SNRNP70 EIF3A PSMD1 RRM1 DDX41 PABPN1 SPINT2 EIF3G PSMD11 RUVBL2 EIF2B3 RPP38 DDX46 PAPOLA SRRT DDX49 PHB2 SUPT5H EIF3I PSMD12 SF3A1 EIF2B4 RPS15 DNM2 PHF5A THOC4 EIF4A3 PSMD7 SF3B3 EIF3E RPS4X DUSP7 PLK1 TIE1 EIF5B RAN SFPQ ECT2 PLRG1 TLR9 HNRNPM RANBP2 SFRS1 EIF3F RUVBL1 EIF1AX POLA1 TM7SF2 ERCC6L POLR2A TMOD3 ITGA2 RBM17 SKIV2L2 EIF3FP3 SFRS2 ERH POLR2D TRPV6 KARS RPA2 SNRNP200 EXOSC10 PRDM16 TSG101 LSM4 RPL23A SNRNP27 EIF3H SMC2 FUT9 PRPF18 TUBA1C LSM5 RPL34 SNRPD1 EIF6 SNRPC GPR112 PRPF19 TXK GREM1 PRPF38A U2AF1 MED30 RPL37 SNRPD2 ESRRG SON GRIN2C PRPF8 U2AF2 NACA RPL5 SNRPE GTF3C4 PSMB4 UBA1 NAPA RPL6 SNRPG HINFP STRN HLA-DRB3 PSMC2 UBB NHP2L1 RPL7 SUPT6H HNRNPK TAF7L HNRNPC PSMD3 VWCE NUP93 RPS11 USP39 HNRNPU PSMD8 WBP11 IQGAP1 TDRD3 HSPA9 PTPN9 XAB2 PCBP2 RPS13 VCP HSPG2 RAD51 XBP1 PHB RPS15A ZNF207 KRAS TRRAP ICK RBMXL1 ZNF471 POLR2I RPS17 TUBB IGFBP2 RFC4 MAPKAP1 INSR RGS18 MED14 USP44 IRS4 RPA1 NAPG VLDLR NCL ZNRF2
Marcotte Cheung
GARP CE’s not in BROAD 54k library C12orf66 KLHL14 RPL30 C14orf2 KPNB1 RPL35 C16orf72 MDN1 RPL35A C22orf27 MS4A13 RPL36 80 125 205 C3orf39 NUF2 RPL37A C9orf30 NUP133 RPL39 CCT3 NUP88 RPL4 CCT7 NUS1 RPL7A 54 10926 10980 CCT8 PSMD6 RPL9 CEND1 RFTN1 RPLP0 CMTM3 RILPL2 RPLP1 COPB1 RPL10 RPS20 CYorf15A RPL10A RPS26 DYNC1I2 RPL11 RPSAP58 134 11051 11185 EIF3B RPL12 SDAD1 EIF3C RPL13 SEC61A1 EIF3D RPL14 SFRS1 EIF4E3 RPL17 STAG2 -109 FAM126A RPL18 TEKT2 FET p < 1.6 x 10 FAM164C RPL18A TIGD2 FNDC7 RPL19 TMEM5 FTSJ3 RPL23 TUBA1B GLIPR1L2 RPL24 TUBGCP2 GPC6 RPL27 WDR12 Supplemental Figure 4A INTS9 RPL3 131 genes 134 genes n = 58 n = 61
ATXN7 OPA1 AURKB PRPF18 n = 73 BPTF PCBP2 CCNB3 PRPF19 C14orf166 PDZK1IP1 CDC40 PSMC2 COPS6 PSMA2 CDK11B RFC4 ANAPC4 PRPF3 RPS29 COPS8 PSMB6 CLTC RPA1 AQR PRPF31 RPS3A CSE1L PSMC3 COPA RPL31 ARCN1 PSMA1 RPS6 CYP27C1 PSMD12 COPS2 RPL32 CDC5L PSMA3 RPS7 COPZ1 RPS14 CHD4 PSMA6 RPS8 DDX21 PTPRC DDX18 RPS18 DYNC1H1 PSMB2 RPS9 DDX51 RANBP2 DNM2 RPS19 EEF2 PSMB3 RPSA DLC1 RBMX EIF1AX RPS3 EFTUD2 PSMC4 RRM1 EGFLAM REXO2 FUT9 RPTOR EIF2S2 PSMD1 RUVBL2 EIF2B3 ROD1 GPR112 SF3A2 EIF3A PSMD11 SF3A1 EIF2B4 RPP38 HNRNPC SF3B1 EIF3G PSMD7 SF3B3 EIF3E RPS15 HNRNPU SF3B2 EIF3I RAN SFPQ EIF3F RPS25 HSPA9 SF3B5 EIF4A3 RBM17 SFRS1 EIF3FP3 RPS4X HSPG2 SHFM1 EIF5B RPA2 SFRS2 IGFBP2 SKAP1 HNRNPM RPL23A SNRNP200 EIF3H RUVBL1 IRS4 SNRNP70 KARS RPL34 SNRNP27 EIF6 SKIV2L2 LSM3 SPINT2 KRAS RPL37 SNRPD1 ESRRG SMC2 LSM6 SUPT5H LSM4 RPL5 SNRPD2 HINFP SNRPC NUDT21 THOC4 LSM5 RPL6 SNRPE HNRNPK SON NUP205 TIE1 NACA RPL7 SNRPG IQGAP1 STRN NXF1 TLR9 NAPA RPS11 USP39 ITGA2 SUPT6H PABPN1 TUBA1C NHP2L1 RPS13 VCP MAPKAP1 TAF7L PAPOLA U2AF1 NUP93 RPS15A ZNF207 MED14 TDRD3 PHF5A U2AF2 PHB RPS17 PLK1 UBA1 POLR2I RPS27A MED30 TRRAP POLR2A NAPG TUBB POLR2D NCL USP44 NID2 VLDLR NUPL1 ZNRF2 OIP5
Marcotte Cheung
GARP CE’s not in BROAD 54k library C12orf66 RILPL2 RPL35A 73 58 131 C3orf39 RPL10 RPL36 CCT3 RPL10A RPL37A CCT7 RPL11 RPL4 CCT8 RPL12 RPL7A 61 10993 11054 COPB1 RPL13 RPL9 EIF3B RPL14 RPLP0 EIF3C RPL17 RPS20 EIF3D RPL18 RPS26 EIF4E3 RPL18A RPS27 FAM126A RPL19 RPS28 134 11051 11185 FTSJ3 RPL23 RPSAP58 KPNB1 RPL24 TEKT2 MS4A13 RPL27 TUBA1B NUF2 RPL3 TUBGCP2 -114 NUP133 RPL30 FET p < 8.2 x 10 PSMD6 RPL35
Supplemental Figure 4B 0.0 0.2 0.4 0.6 0.8 1.0 PL45 BT20 T47D OV90 Cal51 HPAC HPDE Panc1 A2780 BT549 BT474 , AsPC1 BxPC3 CFPAC HCC38 SW527 - R; Hs766T Hs578T Capan2 OV1946 HP + SW1990 MiaPaca SU86.86 OVCAR8 OVCAR5 OVCAR3 609050M : - TOV1946 HCC1187 HCC1937 HCC1428 HCC1500 HCC1419 HCC1806 HCC1954 HCC1143 HCC1395 O< Panc02.03 Panc08.13 Panc04.03 Panc10.05 Panc03.27 Panc05.04 TOV2223G TOV3133G PaTu8988T A2780_CIS PaTu8988S MD MD MD MD MD MD - OVCA1369_TR OVCA433_Bast OVCAR432_Bast
Breast Ovarian Pancreatic
Supplemental Figure 5 REACTOME_METABOLISM_OF_PROTEINS REACTOME_INFLUENZA_LIFE_CYCLE REACTOME_CHAPERONIN_MEDIATED_PROTEIN_FOLDING 5 REACTOME_SCF_BETA_TRCP_MEDIATED_DEGRADATION_OF_EMI1 REACTOME_DIABETES_PATHWAYS REACTOME_FORMATION_OF_THE_TERNARY_COMPLEX_AND_SUBSEQUENTLY_THE_43S_COMPLEX REACTOME_MRNA_SPLICING REACTOME_VIF_MEDIATED_DEGRADATION_OF_APOBEC3G 4 BIOCARTA_PARKIN_PATHWAY REACTOME_REGULATION_OF_ORNITHINE_DECARBOXYLASE REACTOME_STABILIZATION_OF_P53 REACTOME_TRANSPORT_OF_MATURE_MRNA_DERIVED_FROM_AN_INTRON_CONTAINING_TRANSCRIPT 3 REACTOME_CDT1_ASSOCIATION_WITH_THE_CDC6_ORC_ORIGIN_COMPLEX REACTOME_MRNA_SPLICING_MINOR_PATHWAY KEGG_PROTEASOME KEGG_HUNTINGTONS_DISEASE REACTOME_P53_INDEPENDENT_DNA_DAMAGE_RESPONSE 2 REACTOME_METABOLISM_OF_AMINO_ACIDS KEGG_TRYPTOPHAN_METABOLISM REACTOME_SYNTHESIS_OF_DNA REACTOME_FORMATION_AND_MATURATION_OF_MRNA_TRANSCRIPT REACTOME_M_G1_TRANSITION 1 REACTOME_APOPTOSIS REACTOME_ORC1_REMOVAL_FROM_CHROMATIN REACTOME_ELONGATION_AND_PROCESSING_OF_CAPPED_TRANSCRIPTS REACTOME_INTEGRATION_OF_ENERGY_METABOLISM 0 REACTOME_POST_CHAPERONIN_TUBULIN_FOLDING_PATHWAY KEGG_CELL_CYCLE REACTOME_TRANSLATION_INITIATION_COMPLEX_FORMATION REACTOME_INACTIVATION_OF_APC_VIA_DIRECT_INHIBITION_OF_THE_APCOMPLEX KEGG_RNA_DEGRADATION KEGG_OXIDATIVE_PHOSPHORYLATION REACTOME_TRANSCRIPTION_OF_THE_HIV_GENOME REACTOME_SIGNALING_BY_WNT REACTOME_FORMATION_OF_TUBULIN_FOLDING_INTERMEDIATES_BY_CCT_TRIC REACTOME_CYCLIN_E_ASSOCIATED_EVENTS_DURING_G1_S_TRANSITION_ KEGG_PARKINSONS_DISEASE REACTOME_HOST_INTERACTIONS_OF_HIV_FACTORS REACTOME_HIV_LIFE_CYCLE REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21 REACTOME_G1_S_TRANSITION REACTOME_AUTODEGRADATION_OF_CDH1_BY_CDH1_APC REACTOME_CELL_CYCLE_CHECKPOINTS REACTOME_TRANSPORT_OF_THE_SLBP_INDEPENDENT_MATURE_MRNA REACTOME_DNA_REPLICATION_PRE_INITIATION KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS REACTOME_SNRNP_ASSEMBLY KEGG_PYRIMIDINE_METABOLISM REACTOME_LATE_PHASE_OF_HIV_LIFE_CYCLE REACTOME_MITOTIC_M_M_G1_PHASES REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA REACTOME_REGULATION_OF_APC_ACTIVATORS_BETWEEN_G1_S_AND_EARLY_ANAPHASE KEGG_SPLICEOSOME REACTOME_S_PHASE REACTOME_CDC20_PHOSPHO_APC_MEDIATED_DEGRADATION_OF_CYCLIN_A REACTOME_METABOLISM_OF_RNA REACTOME_HIV_INFECTION REACTOME_GENE_EXPRESSION REACTOME_CELL_CYCLE_MITOTIC BIOCARTA_ETS_PATHWAY BIOCARTA_LAIR_PATHWAY REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS REACTOME_INSULIN_SYNTHESIS_AND_SECRETION REACTOME_IMMUNOREGULATORY_INTERACTIONS_BETWEEN_A_LYMPHOID_AND_A_NON_LYMPHOID_CELL KEGG_LEISHMANIA_INFECTION REACTOME_POST_NMDA_RECEPTOR_ACTIVATION_EVENTS REACTOME_INNATE_IMMUNITY_SIGNALING REACTOME_TOLL_LIKE_RECEPTOR_9_CASCADE REACTOME_SIGNALING_IN_IMMUNE_SYSTEM BREAST PANCREATIC
Supplemental Figure 6 A) B)
C) D)
E)
Supplemental Figure 7 A) B) chr8 chr12 (q23.1-q24.12) (p13.1-p.3) ‡ ‡ ‡ ‡ ‡ MGP EPS8 ART4 LMO3 DERA RERG PLCZ1 ERP27 PDE6H STRAP PTPRO WBP11 MGST1 RERGL EXT1 CAPZA3 ENY2 MAL2 SYBU TRHR EIF3H PIK3C2G C12orf60 C12orf69 UTP23 TRPS1 ARHGDIB PLEKHA5 RAD21 MED30 EBAG9 KCNV1 CSMD3 SLC15A5 C8orf85 TMEM74 SAMD12 NUDCD1 SLC30A8 PKHD1L1 COLEC10 75% 75% TNFRSF11B 50% 50% 25% 25% 0 0 25% 25% Breast
50% Breast 75% 75% 75% 50% 50% 25% 25% 0 0 25% 50% 25% Ovarian 75% Ovarian 75% 75% 50% 50% 25% 25% 0 25% 0 50% 25% Pancreatic
Fraction of amplified or high−scoringFraction lines 75%
Pancreatic of amplified or high−scoringFraction lines 50%
C) D)
chr2 (q32.1) chr1 (q21.3) ‡ ‡ ‡ TFPI FRZB ITGAV DIRC1 SSFA2 NUP35 GULP1 PDE1A CTSS WDR75 CTSK ARNT ENSA ZC3H15 BNIPL ZSWIM2 DUSP19 COL3A1 COL5A2 LASS2 CALCRL NCKAP1 ANXA9 PRUNE SCNM1 TMOD4 ZNF804A SLC40A1 FAM171B MLLT11 C1orf56 DNAJC10 PPP1R1C FAM63A LYSMD1 SETDB1 SEMA6C GABPB2 GOLPH3L HORMAD1 CDC42SE1 50% TNFAIP8L2 25% 50% 0 25% 0 25% Breast 25% 50% Breast 50% 50% 50% 25% 25% 0 0 25%
Ovarian 25% 50% 50% Ovarian
50% 50% c 25% 25% 0 0 25% 25%
Fraction of amplified or high−scoringFraction lines 50%
50% Pancreati Fraction of amplified or high−scoringFraction lines Pancreatic
amplified in cell lines GARP amplified in tumors
Supplemental Figure 8 E) F) chr18 chr17 (p11.23-p11.21) (q21.32) ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ SP6 SP2 CBX1 PNPO SNX11 COPZ2 SKAP1 SCRN2 HOXB7 HOXB1 HOXB2 HOXB4 HOXB6 HOXB8 HOXB9 HOXB3 HOXB5 NFE2L1 PRR15L VAPA GNAL NAPG IMPA2 CIDEA RAB12 RAB31 MPPE1 PTPRM TWSG1 CDK5RAP3 PPP4R1 LRRC30 FAM38B NDUFV2 RALBP1 TXNDC2 APCDD1 LOC404266 CHMP1B KIAA0802 ANKRD12 50%
LOC100192426 25% 50% 0 25% 25% 0 50% Breast 25% 75% 50% Breast 75% 50% 50% 25% 25% 0 0 25% 25% 50% Ovarian 50% Ovarian 75% 75% 50% 50% 25% 25% 0 0 25% 25% 50% 50% Pancreatic Fraction of amplified or high−scoringFraction lines
Fraction of amplified or high−scoringFraction lines 75% 75% Pancreatic
amplified in cell lines GARP amplified in tumors
Supplemental Figure 8 (cont’d)