Cancer uk 2015_module1_ouellette_ver02

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NCRI Cancer Conference:Cancer data and its analysis

practical workshopNovember 1, 2015

2Module #: Title of Module

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NCRI Workshop 2015 – Module 1

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Slides are on slideshare.net• http://www.slideshare.net/bffo/cancer-uk-

2015module1ouellettever02

Module 1Cancer genomic databases

B.F. Francis OuelletteAssociate Director, Informatics and Biocomputing

Ontario Institute for Cancer ResearchNovember 1, 2015

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@bffo

[email protected]

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Schedule for Module 1:Cancer Genomic Databases

• Introduction to the Canadian Bioinformatics Workshop series.

• The Databases: – The Cancer Genome Atlas (TCGA)– The International Cancer Genome Consortium

(ICGC)• Data Access: human genomes and security

and privacy issues: Open Data vs. Controlled Access

data• Another Database:

– The Catalogue of Somatic Mutations in Cancer (COSMIC)

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http://bioinformatics.ca/

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http://bioinformatics.ca/workshops/2015/bioinformatics-cancer-genomics-2015

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Workshops planned for 2016: http://bioinformatics.ca/workshops

1. Bioinformatics for Cancer Genomics2. High-throughput Biology: From Sequence to Networks (2017 -

CSHL)3. Introduction to R4. Exploratory Analysis of Biological Data using R5. Informatics for RNA-sequence Analysis6. Informatics on High Throughput Sequencing Data7. Pathway and Network Analysis of -omics Data8. Informatics and Statistics for Metabolomics9. Analysis of Metagenomic Data10. How to Work in the Cloud: Computing on Human

Genome Data11. Epigenomic Data Analysis12. Big Data in Precision Genomics

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http://bioinformatics.ca/workshops/2015

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E-mail: [email protected]

Web: http://bioinformatics.ca

Workshop announcement mailing list:

http://bioinformatics.ca/mailman/listinfo/announce

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Soap-Box time!• Open Access, Open Data and Open Source are essential for good

Science.• Openness is a responsibility, an obligation, and something that

comes with the privilege of doing publicly funded work.

Open AccessOpen Source

Open Data

Opencourseware

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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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Cancer: a Disease of the Genome

Challenge in Treating Cancer: Every tumour is different Every cancer patient is different

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https://en.wikipedia.org/wiki/List_of_databases_for_oncogenomic_research

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Papers (PMID)– TCGA: 24071849 21720365

23000897 22960745 22810696

24476821– ICGC: 20393554– COSMIC: 25355519– Data Access: 22807659

http://www.ncbi.nlm.nih.gov/pubmed/[PMID]

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TCGAThe Cancer Genome Atlas is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

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About the TCGA• National Cancer Institute (NCI)• National Human Genome Research Institute

(NHGRI)• Phased Structure:

– Three-year pilot in 2006 with an investment of $50 million from each

– TCGA will collect and characterize more than 20 additional tumour types

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Where to start with the TCGA?

Wiki: https://wiki.nci.nih.gov/display/TCGA/About+TCGA

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Division of Labour• Biospecimen Core Resource (BCR)

– centre where samples are carefully catalogued, processed, qualitychecked and stored along with participant clinical information

• Genome Sequencing Centre (GSC)– uses high-throughput methods to identify changes to DNA

sequences that are associated with specific cancer types• Genome Characterization Centre (GCC)

– uses high-throughput technologies to analyze genomic changes involved in cancer

• Genome Data Analysis Centre (GDAC)– provides novel informatics tools to the research community– provides analysis results using TCGA data.

• Data Coordinating Centre (DCC)– Central provider of TCGA data.– Standardizes data formats and validates submitted data.

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TCGA Data• Sequence reads from newer sequencing

technologies are available at the Cancer Genome Hub: https://cghub.ucsc.edu/

• Higher level sequence data (variation calls and abundance measures) are available at the TCGA Portal: http://cancergenome.nih.gov/

• Also integrated with ICGC data (more on this later)


TCGA data flow

http://goo.gl/b5nojx

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Data Coordinating Centre• Play a central role

– Receiving data from BCR, GSC and GCC sites– Providing access to users– Performing analysis of data

• Responsibilities:– Protecting participant privacy and confidentiality– Developing data standards and controlled

vocabularies– Establishing informatics pipelines for data flow– Developing new analytical and visualization

technologies to facilitate data analysis, for all audiences

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TCGA DCC Data Portal• Provides a platform to search, download and

analyze TCGA data sets• Two data access tiers: Open and Controlled• Analytic tools include: Cancer Molecular

Analysis and Cancer Genome Workbench (NCBIB), Integrative Genomics Viewer (Broad) and CancerGenomics Analysis (MSKCC).

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TCGA Data Browserhttps://tcga-data.nci.nih.gov/tcga/

Query TCGAdata onlineusing theTCGA DataBrowser

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The International Cancer Genome Consortium (ICGC)

• http://www.icgc.org/

• “ICGC was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe”


ICGC Map – February 201585 projects launched

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ICGC datasets to date: https://dcc.icgc.org/projects/history




Select “Pancreatic cancer – Canada”


… But where is the data?



http://dcc.icgc.org/

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DACO

ICGC

dbGaP

EGA

TCGA

BAM

Open

Open

ERA

BAM

Germ

Line

+ EGA id

BAMBA

M

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ICGCBAM/FASTQ

TCGABAM/FASTQ

ICGCOpenData

(includes TCGA

Open Data)

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ICGC

TCGA


ICGC

TCGA

Differences between ICGC & TCGA• Different tumour types• Different geographic rules• Many countries vs one jurisdiction• Different definitions of what is controlled• Different data access rules


• Detailed Phenotype and Outcome data

• Gene Expression (probe-level data)

• Raw genotype calls

• Gene-sample identifier links

• Genome sequence files

• Germ line variants

ICGC Controlled Access Datasets

• Cancer Pathology Histologic type or subtypeHistologic nuclear grade• Patient/Person Gender, Age range, Vital status, Survival timeRelapse type, Status at follow-up• Gene Expression (normalized)• DNA methylation • Computed Copy Number and

Loss of Heterozygosity• Somatic variants from Exome or WGS

ICGC OpenAccess Datasets

http://goo.gl/w4mrV


• Primary sequence data (BAM and FASTQ files)

• SNP6 array level 1 and level 2 data• Exon array level 1 and level 2 data• Somatic variants from whole

genome sequencing• Certain information in MAFs• A full list of controlled-access

data types can be found at: http://goo.gl/K1h7zu

TCGA Controlled Access Datasets

• De-identified clinical and demographic data

• Gene expression data• Copy number alterations in regions

of the genome• Epigenetic data• Summaries of data compiled across

individuals• Anonymized single amplicon DNA

sequence data• Somatic variants from scrubbed

exome sequencing

TCGA OpenAccess Datasets

http://goo.gl/A1rMRB

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TCGA/ICGC users agreed:• … to keep all computer systems on which

controlled access data reside, or which provide access to such data, up to date with respect to software and security patches.

• … to protect Controlled Access Data against disclosure to unauthorized individuals.

• … to monitor and control which individuals have access to Controlled Access Data.

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TCGA/ICGC users agreed:• … to destroy all copies of controlled access

data after controlled access privileges expires.

• ... to only use secure transfer protocols: e.g. https and sftp

• … to encrypt Controlled Access data in transfers and storage


What does it mean for this file?

simple_somatic_mutation.aggregated.vcf.gzhttps://dcc.icgc.org/repository/icgc/release_19/Summary




Identify yourself

Fill 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


http://icgc.org/daco





• Name• Institution• Title of Project• Collaborators• Research Summary• Lay Summary• Ethics

• IT Security

• Cloud Storage

• Agreement• Appendices



http://goo.gl/2UVLDJ





DACO approved projects

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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 approvedby DACO

user accounts activated


Catalogue of Somatic Mutations in Cancer (COSMIC)

• http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/

• COSMIC is designed to store and display somatic mutation information and related details and contains information relating to human cancers.

ICGCBAM/FASTQ

TCGABAM/FASTQ

ICGCOpenData

(includes TCGA

Open Data)

COSMICOpen Data

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COSMIC• Somatic Mutations Only• Diverse sources

– Literature (Arrays, Next-Gen, PCR...)– TCGA– ICGC

• Diverse ways to look at data– Gene– Variation– Tumour type– Cell line– Experiment

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FAQ

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Looking up your favorite gene

1 2 3

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In closing• Remember all these sites have great amounts

of documentation• The field is changing quickly, and so are the

portals. • New features are planned as we speak, and so

you need to use the sites, and keep coming back.

• Don’t be afraid to explore• Interested in learning more after today?

Consider one of the bioinformatics.ca workshops!


Acknowledgements: the CBW gang

Michelle Brazas

MichaelStromberg

MarcFiume

MichaelBrudno