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The functional impact of the vast majority of cancer somatic mutations remains unknown, representing a critical knowledge gap for implementing precision oncology. Here, we report the development of a moderate-throughput functional genomic platform consisting of efficient mutant generation, sensitive viability assays using two growth factor-dependent cell models, and functional proteomic profiling of signaling effects for select aberrations. We apply the platform to annotate >1,000 genomic aberrations, including gene amplifications, point mutations, indels, and gene fusions, potentially doubling the number of driver mutations characterized in clinically actionable genes. Further, the platform is sufficiently sensitive to identify weak drivers. Our data are accessible through a user-friendly, public data portal. Our study will facilitate biomarker discovery, prediction algorithm improvement, and drug development.
Pubmed ID: 29533785 RIS Download
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A database for functional prediction and annotation of all potential non-synonymous single-nucleotide variants (nsSNVs) in the human genome. Version 2.0 is based on the Gencode release 9 / Ensembl version 64 and includes a total of 87,347,043 nsSNVs and 2,270,742 essential splice site SNVs. It compiles prediction scores from six prediction algorithms (SIFT, Polyphen2, LRT, MutationTaster, MutationAssessor and FATHMM), three conservation scores (PhyloP, GERP++ and SiPhy) and other related information including allele frequencies observed in the 1000 Genomes Project phase 1 data and the NHLBI Exome Sequencing Project, various gene IDs from different databases, functional descriptions of genes, gene expression and gene interaction information, etc. Some dbNSFP contents (may not be up-to-date though) can also be accessed through variant tools, ANNOVAR, KGGSeq, UCSC Genome Browser''s Variant Annotation Integrator, Ensembl Variant Effect Predictor and HGMD.
View all literature mentionsPrecision oncology knowledge base which contains information about the effects and treatment implications of specific cancer gene alterations. OncoKB contains detailed information about specific alterations in 418 cancer genes. Each variant entry contains biological effect, prevalence, prognostic information, and treatment implications. Information is curated from various sources, such as guidelines from the FDA, ClinicalTrials.gov, and scientific literature by a network of clinical fellows, research fellows, and faculty members at Memorial Sloan Kettering Cancer Center.
View all literature mentionsSoftware toolkit for a charting library written in pure JavaScript. It offers a way to add interactive charts to a web site or web application.
View all literature mentionsThis monoclonal targets GSK3B
View all literature mentionsThis monoclonal targets ERBB3
View all literature mentionsThis monoclonal targets Fatty Acid Synthase
View all literature mentionsThis monoclonal targets GCN5L2
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets Gys1
View all literature mentionsThis unknown targets FKHRL1, phospho (Ser318 / Ser321)
View all literature mentionsThis monoclonal targets Gab2
View all literature mentionsThis monoclonal targets HIF-1α
View all literature mentionsThis polyclonal targets Glycogen Synthase, phospho (Ser641)
View all literature mentionsThis polyclonal targets Glucose-6-Phosphate Dehydrogenase
View all literature mentionsThis monoclonal targets GATA3
View all literature mentionsThis polyclonal targets Human Phospho-ErbB2 (Y1248) Affinity Purified PAb
View all literature mentionsThis polyclonal targets Granzyme B
View all literature mentionsThis unknown targets Hexokinase II
View all literature mentionsThis monoclonal targets FoxO3a
View all literature mentionsThis monoclonal targets Glutaminase
View all literature mentionsThis unknown targets Heregulin
View all literature mentionsThis polyclonal targets Fra-1 (R-20)
View all literature mentionsThis monoclonal targets Phospho-Histone H2A.X (Ser139)
View all literature mentionsThis monoclonal targets c-erbB-2 / HER-2 / neu Oncoprotein
View all literature mentionsThis recombinant monoclonal targets Fibronectin
View all literature mentionsThis monoclonal targets GCLM antibody [EPR6668]
View all literature mentionsThis polyclonal targets Phospho-GSK-3alpha/beta (Ser21/9)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets FoxM1 (D12D5) XP Rabbit mAb
View all literature mentionsThis monoclonal targets XPF antibody [51]
View all literature mentionsThis monoclonal targets TTF1
View all literature mentionsThis monoclonal targets Progesterone Receptor antibody [Y85]
View all literature mentionsThis monoclonal targets MSI2 antibody [EP1305Y]
View all literature mentionsThis monoclonal targets MEK1
View all literature mentionsThis monoclonal targets FAK
View all literature mentionsThis monoclonal targets MUC1
View all literature mentionsThis monoclonal targets PARK7/DJ1
View all literature mentionsThis monoclonal targets Cdc2
View all literature mentionsThis monoclonal targets CD31
View all literature mentionsThis polyclonal targets CD26 - Spacer region
View all literature mentionsThis monoclonal targets Human Bim
View all literature mentionsThis monoclonal targets BCL2 oncoprotein
View all literature mentionsThis monoclonal targets Bak
View all literature mentionsThis polyclonal targets ATRX antibody
View all literature mentionsThis monoclonal targets Androgen Receptor
View all literature mentionsThis monoclonal targets Acetyl Coenzyme A Carboxylase
View all literature mentionsThis recombinant monoclonal targets Zap-70
View all literature mentionsThis monoclonal targets Ybx1
View all literature mentionsThis polyclonal targets YAP1
View all literature mentionsThis polyclonal targets YAP (H-125)
View all literature mentionsThis polyclonal targets XRCC1
View all literature mentionsThis monoclonal targets XPA (12F5)
View all literature mentionsThis polyclonal targets XBP-1 (R-14)
View all literature mentionsThis polyclonal targets WIPI2
View all literature mentionsThis monoclonal targets Wee1
View all literature mentionsThis unknown targets Wee1
View all literature mentionsThis monoclonal targets VHL
View all literature mentionsThis monoclonal targets VEGF Receptor 2 (55B11) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-ULK1 (Ser757)
View all literature mentionsThis monoclonal targets UGT1A (B-4)
View all literature mentionsThis monoclonal targets Ubiquityl-Histone H2B
View all literature mentionsThis polyclonal targets UBAC1 antibody produced in rabbit
View all literature mentionsThis monoclonal targets Tyro3 (D38C6) Rabbit mAb
View all literature mentionsThis monoclonal targets Genetic locus: TWIST1 (human) mapping to 7p21.1; Twist1 (mouse) mapping to 12 A3. Raised against a recombinant protein corresponding to a region near the C-terminus of twist of human origin.
View all literature mentionsThis monoclonal targets Tuberin, phospho (Thr1462)
View all literature mentionsThis monoclonal targets Tuberin
View all literature mentionsThis polyclonal targets TSC1
View all literature mentionsThis monoclonal targets TRIM25
View all literature mentionsThis monoclonal targets Transglutaminase II, Cellular / Tissue
View all literature mentionsThis polyclonal targets TIGAR
View all literature mentionsThis unknown targets Transferrin Receptor
View all literature mentionsThis polyclonal targets TAZ
View all literature mentionsThis monoclonal targets Tau
View all literature mentionsThis monoclonal targets Human SYK
View all literature mentionsThis monoclonal targets Stmn1
View all literature mentionsThis monoclonal targets STAT5a
View all literature mentionsThis monoclonal targets Phospho-Stat3 (Tyr705)
View all literature mentionsThis recombinant monoclonal targets Stat3
View all literature mentionsThis polyclonal targets Phospho-Src (Tyr527)
View all literature mentionsThis polyclonal targets Phospho-Src Family (Tyr416)
View all literature mentionsThis monoclonal targets Src
View all literature mentionsThis monoclonal targets SOD2
View all literature mentionsThis monoclonal targets SOD1
View all literature mentionsThis monoclonal targets SNAI1
View all literature mentionsThis monoclonal targets Raised against amino acids 1-552 representing full length Smad4 of human origin
View all literature mentionsThis monoclonal targets Smad3
View all literature mentionsThis monoclonal targets Smad1
View all literature mentionsThis monoclonal targets KLHL20
View all literature mentionsThis unknown targets SHP-2, phospho (Tyr542)
View all literature mentionsThis unknown targets Shc, phospho (Tyr317)
View all literature mentionsThis monoclonal targets SRSF1
View all literature mentionsThis monoclonal targets SCD (CD.E10)
View all literature mentionsThis polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein (54D2) Mouse mAb
View all literature mentionsThis unknown targets RSK1 / RSK2 / RSK3
View all literature mentionsThis unknown targets Phospho-RPA32 (Ser4, Ser8)
View all literature mentionsThis monoclonal targets RPA32
View all literature mentionsThis monoclonal targets Phospho-Rictor (Thr1135) (D30A3) Rabbit mAb
View all literature mentionsThis monoclonal targets Rictor (53A2) Rabbit mAb
View all literature mentionsThis monoclonal targets Human/Mouse/Rat Rheb MAb (Clone 344912)
View all literature mentionsThis polyclonal targets Phospho-Rb (Ser807/811)
View all literature mentionsThis monoclonal targets Raptor (24C12) Rabbit mAb
View all literature mentionsThis monoclonal targets RAD51
View all literature mentionsThis monoclonal targets Rad50
View all literature mentionsThis polyclonal targets Rab25
View all literature mentionsThis polyclonal targets RAB11A
View all literature mentionsThis polyclonal targets PREX1 antibody
View all literature mentionsThis unknown targets Phospho-PRAS40 (Thr246)
View all literature mentionsThis monoclonal targets PRAS40
View all literature mentionsThis monoclonal targets VDAC1 / Porin
View all literature mentionsThis monoclonal targets PLK1
View all literature mentionsThis polyclonal targets Plcg2
View all literature mentionsThis monoclonal targets PKM2
View all literature mentionsThis polyclonal targets phospho-PKCdelta (Ser664)
View all literature mentionsThis polyclonal targets Phospho-PKC (pan) (βII Ser660)
View all literature mentionsThis monoclonal targets PKA RI- (D54D9) Rabbit mAb
View all literature mentionsThis polyclonal targets PI3 Kinase p85
View all literature mentionsThis monoclonal targets PI 3-kinase p110beta (B-5)
View all literature mentionsThis polyclonal targets PI3 Kinase p110
View all literature mentionsThis unknown targets Phospho-PEA15 (Ser116)
View all literature mentionsThis polyclonal targets Pea15a
View all literature mentionsThis unknown targets PDK1, phospho (Ser241)
View all literature mentionsThis monoclonal targets PDHK1
View all literature mentionsThis recombinant monoclonal targets PDGFRB
View all literature mentionsThis polyclonal targets Human CD274
View all literature mentionsThis monoclonal targets PD-L1
View all literature mentionsThis monoclonal targets PCNA
View all literature mentionsThis monoclonal targets Paxillin
View all literature mentionsThis polyclonal targets PARP1, PARP2
View all literature mentionsThis polyclonal targets PAR
View all literature mentionsThis polyclonal targets Phospho-p90RSK (Thr573)
View all literature mentionsThis polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentionsThis monoclonal targets S6K
View all literature mentionsThis monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis polyclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
View all literature mentionsThis polyclonal targets p38 MAPK
View all literature mentionsThis polyclonal targets p27 KIP 1 (phospho T198)
View all literature mentionsThis monoclonal targets PSMD9
View all literature mentionsThis unknown targets Raised against a peptide mapping at the carboxy terminus of human p21
View all literature mentionsThis monoclonal targets CDKN2A / p16INK4a
View all literature mentionsThis polyclonal targets P-Cadherin
View all literature mentionsThis polyclonal targets NOTCH3
View all literature mentionsThis monoclonal targets Human Notch1
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis monoclonal targets NDUFB4 antibody [17G3D9E12]
View all literature mentionsThis polyclonal targets NDRG1
View all literature mentionsThis monoclonal targets NAPSIN A antibody [EPR6257]
View all literature mentionsThis unknown targets Myosin heavy chain 11
View all literature mentionsThis polyclonal targets Phospho-mTOR (Ser2448)
View all literature mentionsThis monoclonal targets mTOR
View all literature mentionsThis monoclonal targets Mnk1
View all literature mentionsThis unknown targets MMP-2
View all literature mentionsThis monoclonal targets Human ERRFI1
View all literature mentionsThis unknown targets Merlin
View all literature mentionsThis monoclonal targets Phospho-MEK1/2 (Ser217/221)
View all literature mentionsThis polyclonal targets MDM2, phospho (Ser166)
View all literature mentionsThis polyclonal targets Slc16a3
View all literature mentionsThis monoclonal targets Mcl-1 (D35A5) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (197G2) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-LRP6 (Ser1490)
View all literature mentionsThis monoclonal targets LDHA
View all literature mentionsThis polyclonal targets LC3B
View all literature mentionsThis monoclonal targets Jak2 (D2E12) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Jagged1 antibody [EPR4290]
View all literature mentionsThis polyclonal targets IRF-1 (C-20)
View all literature mentionsThis recombinant monoclonal targets Insulin Receptor beta
View all literature mentionsThis polyclonal targets Inpp4b
View all literature mentionsThis polyclonal targets Igf1r
View all literature mentionsThis polyclonal targets IGFBP-2
View all literature mentionsThis monoclonal targets Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
View all literature mentionsThis polyclonal targets HSP70
View all literature mentionsThis unknown targets HSP27, phospho (Ser82)
View all literature mentionsThis monoclonal targets HSP27
View all literature mentionsThis polyclonal targets pFAK (Tyr397)
View all literature mentionsThis monoclonal targets Human Estrogen Receptor alpha (phospho S118)
View all literature mentionsThis monoclonal targets Estrogen Receptor
View all literature mentionsThis monoclonal targets ENY2
View all literature mentionsThis polyclonal targets Elk1
View all literature mentionsThis polyclonal targets eIF4G
View all literature mentionsThis monoclonal targets eIF4E (phospho S209)
View all literature mentionsThis polyclonal targets eIF4E
View all literature mentionsThis monoclonal targets Human EGFR (phospho Y1137)
View all literature mentionsThis unknown targets EGF Receptor
View all literature mentionsThis monoclonal targets Rb binding domain of E2F-1 p60 protein of human origin
View all literature mentionsThis monoclonal targets E-Cadherin (24E10) Rabbit mAb
View all literature mentionsThis monoclonal targets Histone H3 (di methyl K9)
View all literature mentionsThis polyclonal targets Human Detyrosinated alpha Tubulin
View all literature mentionsThis monoclonal targets Cyclophilin F antibody [E11AE12BD4]
View all literature mentionsThis monoclonal targets cyclin E (HE12)
View all literature mentionsThis monoclonal targets Cyclin D3 (DCS22) Mouse mAb
View all literature mentionsThis polyclonal targets CCND1, CCND2
View all literature mentionsThis monoclonal targets Human Cyclin B1
View all literature mentionsThis monoclonal targets CREB
View all literature mentionsThis monoclonal targets COX IV (3E11) Rabbit mAb
View all literature mentionsThis polyclonal targets Connexin 43
View all literature mentionsThis polyclonal targets COL6A1
View all literature mentionsThis unknown targets Claudin 7
View all literature mentionsThis monoclonal targets CHEK2
View all literature mentionsThis monoclonal targets Chk2
View all literature mentionsThis monoclonal targets CHEK1
View all literature mentionsThis monoclonal targets Chek1
View all literature mentionsThis monoclonal targets Phospho-cdc2 (Tyr15)
View all literature mentionsThis monoclonal targets cdc25C (5H9) Rabbit mAb
View all literature mentionsThis monoclonal targets CD49b
View all literature mentionsThis monoclonal targets Human CD44
View all literature mentionsThis monoclonal targets CD29
View all literature mentionsThis monoclonal targets CD171
View all literature mentionsThis polyclonal targets Cav1
View all literature mentionsThis polyclonal targets Cleaved Caspase-7 (Asp198)
View all literature mentionsThis monoclonal targets active Caspase 3
View all literature mentionsThis monoclonal targets c-Raf, phospho (Ser338)
View all literature mentionsThis monoclonal targets Raf-1 clone AM223
View all literature mentionsThis polyclonal targets MYC
View all literature mentionsThis monoclonal targets Met, phospho (Tyr1234 / Tyr1235)
View all literature mentionsThis monoclonal targets c-Kit antibody [Y145]
View all literature mentionsThis unknown targets c-Jun, phospho (Ser73)
View all literature mentionsThis monoclonal targets c-IAP2
View all literature mentionsThis monoclonal targets BRD4
View all literature mentionsThis monoclonal targets BiP
View all literature mentionsThis polyclonal targets BID (Human Specific)
View all literature mentionsThis polyclonal targets BCL2A1
View all literature mentionsThis unknown targets Bcl-xL
View all literature mentionsThis unknown targets Bad, phospho (Ser112)
View all literature mentionsThis polyclonal targets Phospho-B-Raf (Ser445)
View all literature mentionsThis polyclonal targets β-Catenin
View all literature mentionsThis monoclonal targets Axl (C89E7) Rabbit mAb
View all literature mentionsThis polyclonal targets Aurora B/AIM1
View all literature mentionsThis monoclonal targets ATR
View all literature mentionsThis monoclonal targets ATM protein
View all literature mentionsThis monoclonal targets ATM (D2E2) Rabbit mAb
View all literature mentionsThis monoclonal targets Atg7 (D12B11) Rabbit mAb
View all literature mentionsThis polyclonal targets ARID1A
View all literature mentionsThis monoclonal targets Annexin VII
View all literature mentionsThis monoclonal targets Annexin I
View all literature mentionsThis monoclonal targets AMPK-alpha, phospho (Thr172)
View all literature mentionsThis polyclonal targets AMPK-alpha
View all literature mentionsThis monoclonal targets AMPK alpha 2 (phospho S345) antibody [EPMDAR6]
View all literature mentionsThis monoclonal targets Phospho-Akt (Thr308) (C31E5E) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-Acetyl-CoA Carboxylase (Ser79)
View all literature mentionsThis unknown targets 53BP1
View all literature mentionsThis monoclonal targets Phospho-4E-BP1 (Ser65) (174A9) Rabbit mAb
View all literature mentionsThis polyclonal targets 4E-BP1
View all literature mentionsThis polyclonal targets YWHAZ, YWHAB, SFN
View all literature mentionsThis monoclonal targets 14-3-3 epsilon (8C3)
View all literature mentionsThis polyclonal targets YWHAB
View all literature mentionsThis monoclonal targets HIF-1α
View all literature mentionsThis unknown targets Hexokinase II
View all literature mentionsThis unknown targets Heregulin
View all literature mentionsThis monoclonal targets ERBB3
View all literature mentionsThis polyclonal targets Human Phospho-ErbB2 (Y1248) Affinity Purified PAb
View all literature mentionsThis monoclonal targets c-erbB-2 / HER-2 / neu Oncoprotein
View all literature mentionsThis monoclonal targets Phospho-Histone H2A.X (Ser139)
View all literature mentionsThis polyclonal targets Glycogen Synthase, phospho (Ser641)
View all literature mentionsThis monoclonal targets Gys1
View all literature mentionsThis polyclonal targets Phospho-GSK-3alpha/beta (Ser21/9)
View all literature mentionsThis monoclonal targets GSK3B
View all literature mentionsThis polyclonal targets Granzyme B
View all literature mentionsThis monoclonal targets Glutaminase
View all literature mentionsThis monoclonal targets GCN5L2
View all literature mentionsThis monoclonal targets GCLM antibody [EPR6668]
View all literature mentionsThis monoclonal targets GATA3
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets Gab2
View all literature mentionsThis polyclonal targets Glucose-6-Phosphate Dehydrogenase
View all literature mentionsThis polyclonal targets Fra-1 (R-20)
View all literature mentionsThis unknown targets FKHRL1, phospho (Ser318 / Ser321)
View all literature mentionsThis monoclonal targets FoxO3a
View all literature mentionsThis monoclonal targets FoxM1 (D12D5) XP Rabbit mAb
View all literature mentionsThis recombinant monoclonal targets Fibronectin
View all literature mentionsThis monoclonal targets Fatty Acid Synthase
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets FoxM1 (D12D5) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Fatty Acid Synthase
View all literature mentionsThis monoclonal targets FoxO3a
View all literature mentionsThis unknown targets FKHRL1, phospho (Ser318 / Ser321)
View all literature mentionsThis polyclonal targets Fra-1 (R-20)
View all literature mentionsThis polyclonal targets Glucose-6-Phosphate Dehydrogenase
View all literature mentionsThis recombinant monoclonal targets Fibronectin
View all literature mentionsThis monoclonal targets GCN5L2
View all literature mentionsThis monoclonal targets GATA3
View all literature mentionsThis monoclonal targets Gab2
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Granzyme B
View all literature mentionsThis monoclonal targets GSK3B
View all literature mentionsThis monoclonal targets Glutaminase
View all literature mentionsThis monoclonal targets GCLM antibody [EPR6668]
View all literature mentionsThis monoclonal targets HIF-1α
View all literature mentionsThis unknown targets Hexokinase II
View all literature mentionsThis unknown targets Heregulin
View all literature mentionsThis monoclonal targets ERBB3
View all literature mentionsThis polyclonal targets Human Phospho-ErbB2 (Y1248) Affinity Purified PAb
View all literature mentionsThis monoclonal targets c-erbB-2 / HER-2 / neu Oncoprotein
View all literature mentionsThis monoclonal targets Phospho-Histone H2A.X (Ser139)
View all literature mentionsThis polyclonal targets Glycogen Synthase, phospho (Ser641)
View all literature mentionsThis monoclonal targets Gys1
View all literature mentionsThis polyclonal targets Phospho-GSK-3alpha/beta (Ser21/9)
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