international cancer genomics consortium (icgc) data coordinating center

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The International Cancer Genome Consortium (ICGC) Data Coordinating Center (DCC) November 14 th 2013 B.F. Francis Ouellette [email protected] Senior Scientists & Associate Director, Informatics and Biocomputing, Ontario Institute for Cancer Research, Toronto, ON Associate Professor, Department of Cell and Systems Biology, University of Toronto, Toronto, ON.

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EBI sponsored oncogenomics workshop presentation from Francis Ouellette

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Page 1: International Cancer Genomics Consortium (ICGC) Data Coordinating Center

The International Cancer Genome

Consortium (ICGC) Data Coordinating

Center (DCC)

November 14th 2013

B.F. Francis Ouellette [email protected]

• Senior Scientists & Associate Director,

Informatics and Biocomputing, Ontario Institute for

Cancer Research, Toronto, ON

• Associate Professor, Department of Cell and Systems Biology,

University of Toronto, Toronto, ON.

Page 2: International Cancer Genomics Consortium (ICGC) Data Coordinating Center

2Module #: Title of Module

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You are free to:

Copy, share, adapt, or re-mix;

Photograph, film, or broadcast;

Blog, live-blog, or post video of;

This presentation. Provided that:

You attribute the work to its author and respect the rights

and licenses associated with its components.

Slide Concept by Cameron Neylon, who has waived all copyright and related or neighbouring rights. This slide only ccZero.

Social Media Icons adapted with permission from originals by Christopher Ross. Original images are available under GPL at;

http://www.thisismyurl.com/free-downloads/15-free-speech-bubble-icons-for-popular-websites

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@bffo

[email protected]

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Disclaimer

I do not (and will not) profit in any way, shape or form,

from any of the brands, products or companies I may

mention.

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Cancer therapy is like

beating the dog with

a stick to get rid of

his fleas.

- Anna Deavere Smith,

Let me down easy

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http://goo.gl/Yhbsj

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The revolution in cancer

research can summed up

in a single sentence:

cancer is in essence,

a genetic disease.

- Bert Vogelstein

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CancerA Disease of the Genome

Challenge in Treating Cancer:

Every tumor is different

Every cancer patient is different

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Johns Hopkins

> 18,000 genes analyzed for mutations

11 breast and 11 colon tumors

L.D. Wood et al, Science, Oct. 2007

Wellcome Trust Sanger Institute

518 genes analyzed for mutations

210 tumors of various types

C. Greenman et al, Nature, Mar. 2007

TCGA (NIH)

Multiple technologies

brain (glioblastoma multiforme), lung (squamous carcinoma), and ovarian (serous cystadenocarcinoma).

F.S. Collins & A.D. Barker, Sci. Am, Mar. 2007

Large-Scale Studies of Cancer Genomes

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Heterogeneity within and across tumor types

High rate of abnormalities (driver vs

passenger)

Sample quality matters

Lessons learned

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2007

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International Cancer Genome Consortium

• Collect ~500 tumour/normal pairs from each of 50 different major

cancer types;

• Comprehensive genome analysis of each T/N pair:

– Genome

– Transcriptome

– Methylome

– Clinical data

• Make the data available to the research community & public.

Identify

genome

changes

…GATTATTCCAGGTAT… …GATTATTGCAGGTAT… …GATTATTGCAGGTAT…

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Rationale for the ICGC

• The scope is huge, such that no country can do it all.

• Coordinated cancer genome initiatives will reduce

duplication of effort for common and easy to acquire

tumor samples and and ensure complete studies for many

less frequent forms of cancer.

• Standardization and uniform quality measures across

studies will enable the merging of datasets, increasing

power to detect additional targets.

• The spectrum of many cancers varies across the

world for many tumor types, because of environmental,

genetic and other causes.

• The ICGC will accelerate the dissemination of genomic

and analytical methods across participating sites, and

the user community

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International Cancer Genome Consortium

(ICGC)Goals

• Catalogue genomic abnormalities in tumors in 50 different cancer types and/or subtypes of clinical and societal importance across the globe

• Generate complementary catalogues of transcriptomic and epigenomic datasets from the same tumors

• Make the data available to research community rapidly with minimal restrictions to accelerate research into the causes and control of cancer

50 tumor types and/or subtypes

500 tumors + 500 controls per subtype

50,000 Human Genome Projects!

Nature (2010) 464:993

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Analysis Data Types

• Simple Somatic Mutations

• Copy Number Alterations

• Structural Somatic Mutations

• Gene Expression (micro-arrays and RNASeq)

• miRNA Expression (RNASeq)

• Epigenomics (Arrays and Methylation)

• Splicing Variation

• Protein Expression

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OICR’s mission

To build innovative research

programs that will have an impact

on the prevention, early detection,

diagnosis and treatment of

cancer.

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OICR Informatics & Biocomputing Senior Staff

Lincoln Stein

Director, I&B

Sr. PI

Vincent Ferretti

Assoc. Director,

Bioinf. Software Dev

Sr. PI

Francis Ouellette

Assoc. Director, I&B

Paul Boutros

Jr. PI

David Sutton

Director, IT

Tatiana Lomasko

Program Manager

Brian Shoichet

Sr. PI

May 2013

Jared Simpson

OICR Fellow

May 2013

Lakshmi

Muthuswamy

Jr. PI

Paul Boutros

Jr. PI

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http://icgc.org

22

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ICGC Map – November 2013

67 projects launched

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ICGC Committees & Working Groups

http://icgc.org/icgc/committees-and-working-groups

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ICGC Project Teams @ OICR

• ICGC Secretariat

– Executive Chair: Thomas Hudson

– Senior Project Manager: Jennifer Jennings

– Administrative Coordinator: Jaypee Banlawi

• (with the support of the Web Development team)

• ICGC Data Coordination Center (DCC)

– DCC Leader: Lincoln Stein

– DCC Co-Leader: Francis Ouellette

– DCC Software Development Team Leader: Vincent

Ferretti (+6 FTE)

– DCC Data Curation: Hardeep Nahal (+1 FTE)

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DCC ActivitiesDCC activities are split between two groups:

• Software Development– DCC portal

– Submission tool

• Curation (and Content Management)– Data level management

– Submitter “handling”

– Coordination with secratariat

– User support

http://dcc.icgc.org/team

26

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ICGC Data Coordination Centre

A “comprehensive management system” providing:

• Secure mechanism for uploading data

• Track uploads and perform integrity checks

• Regular progress reporting (data audit)

• Quality checks (coverage, correctness, etc.)

• Enable distribution of raw data to public repositories

• Provide essential metadata to public repositories

• Integrate with other public repositories via standard data

formats, ontologies, etc.

27

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ICGC Data Coordination Centre (2)

Provides the following support to experimental

biologists, computational biologists, and other

researchers:

• Download of complete dataset, or subsets

• Restrict protected data to authorized users (controlled access)

• Search data by gene or specimen, or lists thereof

• Interactive system for identifying specimens of interest, finding what

data sets are available for those specimens, selecting data slices

across those specimens (e.g., counts of the number of somatic

mutations observed a region within the UTR of a gene of interest), and

running basic analytic tests on those data slices

28

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ICGC Data Types

• Clinical Data

– Hosted by DCC via data portal– Was 100% open access, but currently 9 data elements have been flagged by DACO

as controlled access and are under review by IDAC

• Experimental Analysis Data

– Hosted by DCC via data portal

– Somatic is open access, germline is controlled

• “Raw” Sequencing Data (+ array data, etc.)

– Hosted at other public repositories

– Primary repository for ICGC sequence data is EBI EGA

– TCGA raw data hosted at CGhub

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ICGC datasets to date

Dec-11 Jan-2012 Feb March April June July Aug Sept OctMay Nov Dec Jan-2013 Feb March April May June July Aug Sept-2013

1000

2000

3000

4000

5000

6000

7000

8000

9000

10,000

Release 7Release 8

Release 9

Release 10

Release 11

Release 12Release 13

Release 14

Number of

Donors

ICGC Data Portal Cumulative Donor Count for Member Projects

Hardeep Nahal

Page 31: International Cancer Genomics Consortium (ICGC) Data Coordinating Center

• Cancer types: 41

• Donors: 8,532 (18,056 specimens)

• Simple somatic mutations: 1,995,134

• Copy number mutations: 18,526,593

• Structural rearrangements: 18,614

• Genes affected* by simple somatic mutations: 22,074

• Genes affected* by non-synonymous coding mutations: 19,150 Genes

affected* by copy number mutations: 20,341

• Genes affected* by structural rearrangements: 1,884

• *out 22,259 protein coding genes annotated in Ensembl Human release 69

• Open tier and controlled data currently available

ICGC dataset version 14

September 2013

Hardeep Nahal

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Key DCC Activities for 2013

• Improved data & metadata curation at EGA; better

linking of data held at DCC to ICGC data in other

repositories (currently not perfect)

• Improved data quality/integrity checking through

new submission/validation system; review of

submission file specifications

• Integration of new data submission system and

portal infrastructure with project and user

information managed at ICGC.org

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Moratorium: http://www.icgc.org/icgc/goals-structure-policies-guidelines/e3-publication-policy

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Where do you find that information?

• We actually make it hard to find, but we are

working on that! (this is an example of where ICGC

would like to do what TCGA does!)

• http://cancergenome.nih.gov/publications/publicatio

nguidelines

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Where do you find that information?

For ICGC data:

• Need to find the policy!• http://icgc.org/icgc/goals-structure-policies-

guidelines/e3-publication-policy

• Find text:

• Published > no embargo

• < 100 tumors > 2 years

• > 100 tumors > 1 year

• Find date: in README on FTP file

• (exception in README)

• This is bad, we know it, and we are fixing it!

• In doubt? Contact us! [email protected]

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Time limits for publication moratoriums:

All data shall become free of a publication moratorium when either:

1) the data is published by the ICGC member project

2) one year after a specified quantity of data (e.g. genome dataset from 100 tumours per project) has been released via the ICGC database or other public databases.

3) In all cases data shall be free of a publication moratorium two years after its initial release.

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DACO

ICGC

dbGaP

EGA

TCGA

BAM

Open

Open

ERA

BA

M

Germ

Line

+ EGA id

BA

MBA

M

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ICGCBAM/FASTQ

TCGABAM/FASTQ

ICGCOpen

Data

(includes

TCGA

Open Data)

COSMICOpen

Data

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Raw Data Availability at EGA by Project and Data Type

• https://www.ebi.ac.uk/ega/organisations/EGAO00000000024

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Cooperation with EBI EGA Repository for

Controlled Access Raw Data

• Concerted efforts with EGA staff to support

coordinated data submissions to both ICGC DCC

& EGA

• Infrastructure to grant controlled data access

automatically on approval of ICGC DACO web

application forms

40

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What the users see?

• Important to have a data portal that represents the

richness of the data that we generate, but to also

make sure biologists and clinicians can actually

use the data & make discoveries!

• Important to have a scalable technology that will

support 50,000 human genomes, and thousands of

concurrent users (we don’t have that many yet)

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Uniform Annotations

• Annotating Simple Somatic Mutations (SSM) and Simple

Germline Variations (SGV)

• DCC is currently implementing the snpEff software

◦ Recommended by the ICGC Bioinformatics Analysis

Working Group

◦ Returns Sequence Ontology's controlled vocabulary

regarding mutation-induced changes

(www.sequenceontology.org)

• ICGC members will not be required to annotate

SSM and SGV for the ICGC data releases

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http://icgc.org

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Select “Pancreatic cancer – Canada”

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… But where is the data?

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http://dcc.icgc.org/

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Highlights of the new portal: dcc.icgc.org

• Faceted searches capabilities for variants, genes and

donors

– Interactive data exploration fast and easy

• Mutation aggregation & counts across donors and cancers

– # of pancreatic cancers donors with mutation KRAS G12D

• Standardized gene consequence across all projects

• Genome browser

• Data doewnload

• Protein domains

• Links to repositories

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Technologies

Chaplin Web GUI

Indexing

Processing

&

Data Model

Core

Brian O’Connor/

Vincent Ferretti

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KRAS search

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• Summary

• Cancer type distribution

• Other links (Cosmic, Entrez, etc)

• Mutation profile in protein

• Domains

• Genomic Context

• Mutation profile

• Most common mutations

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http://dcc.icgc.org/genes/ENSG00000133703

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http://goo.gl/qUzuAi

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Donor• Donor ID

• Primary site

• Cancer Project

• Gender

• Tumor Stage

• Vital Status

• Disease Status

• Release type

• Age at diagnosis

• Available data types

• Analysis types

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Genes

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Mutations• Consequences

• Type

• Platform

• Verification status

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Exporting data

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Exporting data

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Exporting data

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Can do bulk download of the data …

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ICGCBAM/FASTQ

TCGABAM/FASTQ

ICGCOpen

Data

(includes

TCGA

Open Data)

COSMICOpen

Data

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DACO

ICGC

dbGaP

EGA

TCGA

BAM

Open

Open

ERA

BA

M

Germ

Line

+ EGA id

BA

MBA

M

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ICGC Data Categories

ICGC Open Access Datasets ICGC Controlled Access Datasets

Cancer Pathology

Histologic type or subtype

Histologic nuclear grade

Donor

Gender

Age range

RNA expression (normalized)

DNA methylation

Genotype frequencies

Somatic mutations (SNV,

CNV and Structural

Rearrangement)

Detailed Phenotype and Outcome Data

Patient demography

Risk factors

Examination

Surgery/Drugs/Radiation

Sample/Slide

Specific histological features

Protocol

Analyte/Aliquot

Gene Expression (probe-level data)

Raw genotype calls (germline)

Gene-sample identifier links

Genome sequence files

Most of the data in the portal is publically available without restriction. However,

access to some data, like the germline mutations, requires authorization by the Data

Access Compliance Office (DACO)

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Module 1: Cancer Genomic Databases bioinformatics.ca

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Module 1: Cancer Genomic Databases bioinformatics.ca

http://icgc.org/daco

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• Detailed Phenotype and Outcome data

Region of residence

Risk factors

Examination

Surgery

Radiation

Sample

Slide

Specific histological features

Analyte

Aliquot

Donor notes

• Gene Expression (probe-level data)

• Raw genotype calls

• Gene-sample identifier links

• Genome sequence files

ICGC Controlled

Access Datasets

• Cancer Pathology

Histologic type or subtype

Histologic nuclear grade

• Patient/Person

Gender, Age range,

Vital status, Survival time

Relapse type, Status at follow-up

• Gene Expression (normalized)

• DNA methylation

•Computed Copy Number and

Loss of Heterozygosity

• Newly discovered somatic variants

ICGC OA

Datasets

http://goo.gl/w4mrV

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Module 1: Cancer Genomic Databases bioinformatics.ca

Identify

yourselfFill out detail form which

includes:

• Contact and Project

Information

•Information Technology

details and procedures

for keeping data secure

•Data Access Agreement

All of these

documents are

put into a PDF

file that you

print and get your

institution to sign

off on your behalf

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Module 1: Cancer Genomic Databases bioinformatics.ca

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Module 1: Cancer Genomic Databases bioinformatics.ca

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Module 1: Cancer Genomic Databases bioinformatics.ca

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Module 1: Cancer Genomic Databases bioinformatics.ca

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Module 1: Cancer Genomic Databases bioinformatics.ca

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Module 1: Cancer Genomic Databases bioinformatics.ca

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Module 1: Cancer Genomic Databases bioinformatics.ca

DACO approved projects:

59 groups - 75% academic

(~400 people)

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DACO/DCC User Data Access Process

• Users approved through DACO are now automatically granted access to

ICGC controlled access datasets available through the ICGC Data Portal

and the EBI’s EGA repository

DACO Web

Application

DCC User

Registry

DCC Data

Portal

EBI EGA

application

approved

by DACO

user

accounts

activated

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Future Work for the DCC

• Work with projects to improve in a number of areas:

– clinical data content,

– Increasing frequency of data release

• Better metadata collection from the EGA

– Working with EGA to better match metadata requirements for ICGC member

submissions; will enable reliable linking by Sample ID, Donor ID, etc. between data

portal and EGA. Will allow direct link to DACO approved users

– Projects will be required to provide this required metadata at submission time,

existing EGA datasets will be updated.

• Improve access to projects’ analysis methods

– Suggested publishing analysis SOPs in Standards in Genomic Sciences at most

recent ICGC workshop; haven’t seen any interest in doing this from member projects.

– DCC to host centralized web page(s) for each project’s analysis methods; use

permalink in submission files.

• Better documentation … always need more!

• Better transparency of processes

• Better links to publications

85

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Future Work for the DCC

• New releases:– Release 15: finished before Christmas

• All data submission sent in again, plus new data

• (no methylation data)

– Release 16: incremental submission + Methylation data,

released before May

– Release 17: adopt incremental for all data types, and

increase frequency of releases.

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New Project: ICGC PANCANCER analysis

• 2,000 Whole genome sequencing

– 6 cloud infrastructures across the world

– Appropriate policy and tool availability

– Agreed upon shared pipelines, and others

– Shared datasets

– Petabytes of files, 10,000’s cores

– Mutation analysis, as well as CNV, Structural, others

when feasible (RNA and methylome).

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Challenges and Opertunity

• Targetted sequencing for Patient

Selection

• Consent

• Combinations

• Corrected features and #features >>

#samples

• Noisy and incomplete data

• Speed and cost

Adapted from Paul Rejto, Pfizer

We are also hiring!

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FGED’s mission:

To be a positive agent of

change in the effective

sharing and reproducibility

of functional genomic data

fged.org

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DCC Software

Developer

Vincent Ferretti

Brian O’Connor

Junjun Zhang

Anthony Cros

Jonathan Guberman

Bob Tiernay

Shane Wilson

Long Yao

Daniel Chang

Jerry Lam

Stuart Watt

Acknowledgments

ICGC Project leaders at the OICR:

• Tom Hudson

• John McPherson

• Lincoln Stein

• Paul Boutros

• Lakshmi Mutsawarma

• Vincent Ferretti

• Francis Ouellette

• Jennifer Jennings

Ouellette Lab

Michelle Brazas

Emilie Chautard

Nina Palikuca

Matthew Ziembicki

Web Dev

Miyuki Fukuma

Kamen Wu

Joseph Yamada

Salman Badr

Pipeline Development

& Evaluation

Morgan Taschuk

Rob Denroche

Peter Ruzanov

Zhibin Lu

DCC Data Coordinator

Hardeep Nahal

http://oicr.on.ca http://icgc.org

… and all the patients and their

families that that are putting their

hopes into our work!

• FGED

Alvis Brazma

Roger Bumgarner

Cesare Furlanello

Michael Miller

Francis Ouellette

John Quackenbush –

Dana-Farber

Michael Reich

Gabriella Rustici

Chris Stoeckert

Ronald Taylor

Steve Trutane

Jennifer Weller

Brian Wilhelm

Neil Winegarden

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91Informatics and Biocomputing at the OICR

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92Maya et Pascale, 2012

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http://icgc.org

[email protected]

This presentation: http://goo.gl/HP613K

Video tutorial: https://vimeo.com/75522669