Connecting Cancer Genomics to Cancer Biology using Proteomics

Connecting Cancer Genomics to Cancer Biology using Proteomics Nathan Edwards Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center

NCI: CPTAC Phase II l l l Clinical Proteomic Tumor Analysis Consortium (CPTAC): 2011 -2016 Comprehensive study of genomically characterized (TCGA) cancer biospecimens by bottom-up massspectrometry-based proteomics workflows Follows Clinical Proteomics Technology Assessment Consortium (CPTAC Phase I) l CPTAC 3. 0 just starting… 2

NCI: CPTAC Phase II 3

CPTAC-II Data Coordinating Center (DCC) l Partnership between ESAC Inc. and Georgetown ICBI & UIS l l l Subha Madhavan (ICBI), Peter Mc. Garvey (ICBI), Nathan Edwards (BMCB) ESAC: Karen Ketchum (PM), Mauricio Oberti, Ratna Thangudu, Shuang Cai, many others… Recently awarded - CPTAC 3. 0 DCC l Simina Boca (ICBI), Shaojun Tang (ICBI) 4

CPTAC Data Portal l l All data is publicly released… …subject to responsible use guidelines Consortium has 15 months to publish first global analysis http: //grg. tn/cptac Data available in Edwards et al. , J. Proteome Res. , 2015, 14 (6). the meantime. 5

CPTAC Data Portal 6

Three CPTAC-TCGA Studies: Big (Proteomics) Data l l Per study: ~ 100 samples, ~ 1 TB of data, ~ 10 M-50 M spectra Breast, Ovarian, Colorectal Cancer l l l Tumor samples only! Global protein abundance, plus phospho- and glyco- sub-proteomes From TCGA: Exome, RNA-Seq, copy-number l Same tumors! Connect genomics to proteomics! 7

Big Question for CPTAC-II l Henry Rodrigez, Office of Cancer Clinical Proteomics Research, NCI (10/12/2016) l l l Despite the investment in TCGA (34 cancer types, 12, 000 individuals), “missing biology” Can additional (cancer) biology be elucidated from deep proteomic analysis? YES! New molecular cancer subtypes, new drug targets, new biological insight. l CPTAC/TCGA Colorectal cancer study l Zhang, et al. , Nature 513, 382 (2014). 8

Non-synonymous Germline & Somatic Variants Zhang, et al. , Nature 513, 382 (2014). 9

Protein abundance and m. RNA expression are poorly correlated Zhang, et al. , Nature 513, 382 (2014). 10

…except for proteins in metabolic pathways? Zhang, et al. , Nature 513, 382 (2014). 11

Protein abundance is mostly unaffected by copy-number var. Zhang, et al. , Nature 513, 382 (2014). 12

New colorectal cancer subtypes Zhang, et al. , Nature 513, 382 (2014). 13

CPTAC 3. 0 l 6 new cancer types, 200 tumors / study, matched normals. l Proteogenomics is the next big thing: l l Cancer Moonshot (Biden) APOLLO Program (VA) 7 international collaborations with NCI Should be fun! 14