Transcript Nature 513 - Edwards Lab

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
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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)
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CPTAC 3.0 just starting…
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NCI: CPTAC Phase II
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CPTAC-II Data Coordinating
Center (DCC)
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Partnership between ESAC Inc. and
Georgetown ICBI & UIS
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Subha Madhavan (ICBI), Peter McGarvey
(ICBI), Nathan Edwards (BMCB)
ESAC: Karen Ketchum (PM), Mauricio Oberti,
Ratna Thangudu, Shuang Cai, many others…
Recently awarded - CPTAC 3.0 DCC
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Simina Boca (ICBI), Shaojun Tang (ICBI)
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CPTAC Data Portal
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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.
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CPTAC Data Portal
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Three CPTAC-TCGA Studies:
Big (Proteomics) Data
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Per study: ~ 100 samples, ~ 1 TB of data,
~ 10M-50M spectra
Breast, Ovarian, Colorectal Cancer
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Tumor samples only!
Global protein abundance, plus
phospho- and glyco- sub-proteomes
From TCGA: Exome, RNA-Seq, copy-number
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Same tumors! Connect genomics to proteomics!
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Big Question for CPTAC-II
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Henry Rodrigez, Office of Cancer Clinical
Proteomics Research, NCI (10/12/2016)
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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.
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CPTAC/TCGA Colorectal cancer study
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Zhang, et al. , Nature 513, 382 (2014).
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Non-synonymous
Germline & Somatic Variants
Zhang, et al. , Nature 513, 382 (2014).
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Protein abundance and mRNA
expression are poorly correlated
Zhang, et al. , Nature 513, 382 (2014).
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…except for proteins in
metabolic pathways?
Zhang, et al. , Nature 513, 382 (2014).
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Protein abundance is mostly
unaffected by copy-number var.
Zhang, et al. , Nature 513, 382 (2014).
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New colorectal cancer subtypes
Zhang, et al. , Nature 513, 382 (2014).
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CPTAC 3.0
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6 new cancer types, 200 tumors / study,
matched normals.
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Proteogenomics is the next big thing:
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Cancer Moonshot (Biden)
APOLLO Program (VA)
7 international collaborations with NCI
Should be fun!
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