intogen, integrative oncogenomics for personal cancer genomes

IntOGen, Integrative OncoGenomics for personal cancer genomes

Christian Pérez-Llamas

Biomedical Genomics LabPompeu Fabra University

Biomedical Research Park at Barcelona

Oncogenomics data Clinical annotations Biological modules

Transcriptomic alterationsCopy Number alterationsMutations...

InternationalClassificationof Diseasesfor Oncology

FunctionalRegulatoryCancer related...

Integrative methodologies

Cancer related genes identificationCancer related modules identificationCombinations of experiments by ICDOGeneration of cancer specific modules

Web discovery tool Gitools

www.gitools.org

Biomart services

biomart.intogen.orgwww.intogen.org

DA

TAS

TAT

IST

ICS

EX

PL

OR

AT

ION

Data management

Overview

Copy Number Analysisfrom Sanger Institute

Copy number alterationsTranscriptomic alterations Mutations

Selection of experiments

Public dataExperiment design: cancer vs normalAt least 20 samples

Annotation of tumour type

International Classification of Diseases for Oncology (ICD-O)Manual curation from publication or descriptionProgenetix already annotated with ICD-O

More than 800 experimentsMore than 25000 samplesAlmost 150 ICD-O tumor types

Data

identification of driver alterations

STEP 1

exp.

1

samples

genes

not alteredaltered

genes

experiment 1

corrected p-value

0.05 10

Cancer related genes identificationStatistics

identification of driver alterations

STEP 1

exp.

1

+

combination of experiments

STEP 2

exp.

2

exp.

3

exp.

n

Cance

r ty

pe A

samples

genes

not alteredaltered

genes

experiment 1

...

corrected p-value

0.05 10

Cancer related genes identificationStatistics

Statistics Cancer related modules identification


www.gitools.org

Biomart services


Exploration

READS

TUMOURSAMPLE

LONG LISTOF ALTERED

GENES

Cancer gene prioritization with personal genomes

MutationsINDELSDif. Expr.

biomart.intogen.org biomart.intogen.org/martservice

RESTfulWeb service

MartView

biomaRt perl python curl


www.gitools.org

Biomart services


Exploration


www.gitools.org

Biomart services


Exploration

IntOGen: Integration and data-mining of multidimensional oncogenomic data

Gundem G, Perez-Llamas C, Jene-Sanz A, Kedzierska A,Islam A,

Deu-Pons J, Furney S and Lopez-Bigas N.

Nature Methods, 7, 92-93 (2010)

More details...

www.gitools.org

biomart.intogen.org

www.intogen.org

http://www.nature.com/nmeth/journal/v7/n2/full/nmeth0210-92.html

International Cancer Genome Consortium

50 cancer types

500 samples each cancer type

About 25000 genomes in total

Data Storage, Analysis & Management

International Cancer Genome Consortium

50 cancer types

500 samples each cancer type

About 25000 genomes in total

samples

not altered

altered

ICGC-CLL genome project

genes

Cancer genomes in the context of IntOGen

Samples

Technology

Alteration

RNA-seq

Dif. Expression:- Upregulated- Downregulated

7 CLL7 normal

(Roderic Guigo lab)

samples

not altered

altered

genes


tumours / experiments

genes

IntOGen

corrected p-value

0.05 10

Samples

Technology

Alteration

RNA-seq


7 CLL7 normal

(Roderic Guigo lab)


samples

not altered

altered

genes


tumours

genes

IntOGen

corrected p-value

0.05 10

Samples

Technology

Alteration

RNA-seq


7 CLL7 normal

(Roderic Guigo lab)


samples

not altered

altered

genes

samples

path

way

s


corrected p-value

0.05 10

tumours

genes

IntOGen

path

way

s

tumours

corrected p-value

0.05 10

corrected p-value

0.05 10

Enrichmentanalysis

Samples

Technology

Alteration

RNA-seq


7 CLL7 normal

(Roderic Guigo lab)


samples

not altered

altered

genes

samples


corrected p-value

0.05 10

tumours

genes

IntOGen

tumours

corrected p-value

0.05 10

corrected p-value

0.05 10

Enrichmentanalysis

Samples

Technology

Alteration

RNA-seq


7 CLL7 normal

(Roderic Guigo lab)


path

way

s

path

way

s

Considerations for the next version

Ethical

Technological

Ethical considerations

openaccess

controlledaccess

Data that cannot be usedto identify individuals:age, normalized gene expression, ...

Germline genomic data anddetailed clinical informationassociated to a unique individual

openaccess

controlledaccess

Data that cannot be usedto identify individuals:age, normalized gene expression, ...

Germline genomic data anddetailed clinical informationassociated to a unique individual

Ethical considerations

Technical considerations

User interfaces

Infrastructure

Web servicesBrowserGitools BiomartManagement

HadoopMap-Reduce

HadoopDFS Cascading PIG

Grid Engine Plain files MySQL MongoDBBioinformatics

software

IntOGen core

Dataimporters

Analysismanagement

Datamanagement

Experimentsmanagement

Analysisworkflows

Datamodels

Amazon / Eucalyptus


User interfaces

Infrastructure


HadoopMap-Reduce



software

IntOGen core

Dataimporters

Analysismanagement

Datamanagement


Analysisworkflows

Datamodels

Amazon / Eucalyptus

Genome view

NGS workflows

Web management


User interfaces

Infrastructure


HadoopMap-Reduce



software

IntOGen core

Dataimporters

Analysismanagement

Datamanagement


Analysisworkflows

Datamodels

Amazon / Eucalyptus

Genome view

NGS workflows

Web management

Flexibility●Different ways to access the data●Methods constantly evolving●Methods impl. different languages and infrastructure requirements

●Quantity of data increases●And also the number and complexity of calculations

Scalability

Summary

IntOGen is a novel framework for oncogenomics data integration and analysis

It integrates many tumor types and different types of alterations in a common framework

It explores the data at different levels, from individual experiments to combinations of experiments, and from individual genes to biological modules

It incorporates an intuitive web system designed to be a discovery tool for cancer researchers

I have presented some examples on how to use IntOGen and Gitools to prioritize and compare personal genomes data.

We are adapting IntOGen to store, analyze and visualize next generation sequencing data, which will allow to incorporate data from the ICGC, starting by the Chronic Lymphocytic Leukemia data.

Ethical and technological considerations has to be addressed.

Acknowledgements

Nuria López-Bigas

Gunes Gundem

Jordi Deu-Pons

Khademul Islam

Alba Jené-Sanz

Michael Schroeder

Xavier Rafael

Sophia Derdak

Abel Gonzalez-Pérez

Armand Gutierrez

Biomedical Genomics

intogen, integrative oncogenomics for personal cancer genomes

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