the road to personalized medicine is paved with data and information john quackenbushjohn...
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The Road toPersonalized Medicine is
Paved with Data and InformationJohn Quackenbush
NCI Second Generation Sequencing
May 3, 2012
Disease Progression and Personalized Care
TreatmentOptions
QualityOf Life
GeneticRisk
EarlyDetection
Patient Stratification
DiseaseStaging
Outcomes
Natural History of Disease Clinical Care
Environment + Lifestyle
Birth Treatment Death
Biomarkers
Turning the vision into a reality• Assure access to samples and rational consent
• Develop a technology platform
• Make information integration as a central mission
• Conduct research as a vital component
• Present data and information to the local community
• Enable research beyond your own
• Engage corporate partners
• Communicating the mission to the community.
Assure Access to Samples
Access, Research, Security• Patients want to be part of the process of curing disease
• Informed consent needs to be structured to allow patients to be partners in the research process
• HIPPA requires both informed consent and that we assure patient confidentiality
• But “identifiability” is a moving target in a genomic age
• With the <$1000 genome, in the age of Facebook, what this means remains unclear
• The new Genomics is a disruptive technology.
Develop aTechnology Platform
The cost decreases exponentially with time
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Illumina GAIIABI SOLiD
The $1000 Genome:October 2012
Continuing the Regression:Genomes for $100 in February 2014
2010: Enabling a New Era in Genome Analysis
Illumina HiSeq
100Gb (~30X genome coverage)
150bp reads
Two samples/week
<$10,000 per genome
Just Announced: The Life TechnologiesIon Torrent Proton
The Promise from LTI
A Genome in ~24 hours for $1000
Promised in Q3 2012
The USB sequencer
Let the games begin!The Oxford Nanopore MiniON
The Challenge New technologies inspired by the Human
Genome Project are transforming biomedical research from a laboratory science to an information science
We need new approaches to making sense of the data we generate
The winners in the race to understand disease are going to be those best able to collect, manage, analyze, and interpret the data.
Make information integration as a central mission
ClinicalData Metabolomics
ProteomicsTranscriptomics
Cytogenomics
Epigenomics
Genomics
PublishedDatasets
DrugBank
TheHapMap
TheGenome
DiseaseDatabases
(OMIM)
PubMed
ClinicalTrials
ChemicalBiology
Etc.
CentralWarehouse
Improved DiagnosticsIndividualized Therapies
More Effective Agents
Beating Information Overload
Conduct research as a vital component
Data Generation Illumina partnered with us to generate comprehensive
mRNA, microRNA, and methylation, and copy number variation (CNV) profiles on these FFPE ovarian cancer samples
Renee Rubio and Kristina Holton developed protocols for efficient extraction of mRNA/microRNA and genomic DNA from FFPE cores
Quality was validated using BioAnalyzer and hybridizations to Illumina DASL arrays
mRNA/microRNA and DNA were extracted from 132 samples and profiled in collaboration with Illumina on a prototype 12k DASL array
Data were normalized and analyzed using the ISIS class discovery algorithm.
Identifying modules using ISIS*
Module:Set of genes supporting a bi-partition
ISIS searches for stratifications of samples into two groups that maximize a DLD score.
*ISIS: Identifying splits of clear separation (von Heydebreck et al., Bioinformatics 2001)
Module 2 (gene expression)
Module 2Gene set enrichment analysis
Survival and Validation
1606 published ovarian tumors
1090 high grade, late stage serous tumors
Present data and information to the local community
LGRC Research Portal
LGRC Data Download
• Data download
• Browse by basic metadata
• Browse by clinical / phenotype attributes
• Download ‘raw’ data
• Secure transfer via single use ‘tickets’ . Enables authorized users access to the specified result basket for a single session.
LGRC Research Portal
PAGE DETAILS
Search-Facets-Search within results-Keyword prompts-Search history
Table:-Paged results-Sortable columns
Actions:-Go to Gene detail page-Add genes to ‘gene set’
Gene Expression Summary
RNASeq
Annotation Summary
PAGE DETAILS
Annotation summary & summary view for each assay/data type:
Accordion style sections
GEXP – expression profile across major Dx categoriesRNASeq – Exon structure of the geneSNPs – Table of SNPs in region of gene, highlighting association with major Dx group- Methylation – Methylation profile in region around geneGenomic alterations – table of CNVs & alterations observed w/ freq in region around gene
Actions:- Click through to assay detail pageAdd gene to set
LGRC Research Portal
LGRC Research Portal
PAGE DETAILS
- View aggregate statistics-View cohort details-Build cohort sets-Build composite phenotypes
Actions:
-Go to data download for selected cohort -Go to assay detail for selected cohort-Go to cohort manager
LGRC Research Portal
Engage corporate partners
We need to find the best tools We received an $1M Oracle Commitment grant to create
our integrated clinical/research data warehouse
We’ve partnered with IDBS to create data portals
We are working with Illumina on a variety of projects
We are forging relationships with Thomson-Reuters to link genomic profiling data to drug, trial, and patent information
We are building partnerships with Roche, Genomatix, NEB, and others interested in entering the personal genomics space.
Enable research beyondyour own
John Quackenbush, DirectorMick Correll, Associate Director
The MissionThe mission of the CCCB is to provide broad-based support for the analysis and interpretation of ‘omic data and in doing so to further basic, clinical and translational research. CCCB also will conduct research that opens new ways of understanding cancer.
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Infr
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Consulting
CCCB Collaborative Consulting Model
1. Initial meeting to understand project scope and objectives
2. Development of an analysis plan and time/cost estimate
3. During project execution, data and results are exchanged through a secure, password-protected collaboration portal
4. Available as ad-hoc service, or larger scale support agreements
Communicate the mission to the community.
The LGRC
Why Patient Involvement is Essential
Patients want to be our partners in curing disease
The incentive structure in medical research is skewed away from success We all say, “We want to cure disease.” We mean, “We want to cure disease, but only if I am
the one to cure disease.”
The only way to break the logjam is to have patients involved in the process.
Genomics is here to stay
http://compbio.dfci.harvard.edu
AcknowledgmentsThe Gene Index TeamCorina AntonescuValentin AntonescuFenglong LiuGeo PerteaRazvan SultanaJohn Quackenbush
Array Software Hit TeamKatie FranklinEleanor HoweJohn QuackenbushDan SchlauchRaktim SinhaJoseph White
Eskitis InstituteChristine WellsAlan Mackay-Sim
Center for CancerComputational BiologyMick CorrellVictor ChistyakovHowie GoodellLan HuiLev KuznetsovNiall O'ConnorJerry PapenhausenYaoyu WangJohn Quackenbushhttp://cccb.dfci.harvard.edu
Gene Expression Team Fieda AbderazzaqStefan BentinkAedin CulhaneKathleen Fleming Benjamin Haibe-KainsJessica MarMelissa MerrittMegha PadiRenee Rubio
(Former) Stellar StudentsMartin AryeeKaveh Maghsoudi Jess Mar
Systems SupportStas Alekseev, Sys AdminPriya Karanam, DBA
Administrative SupportJoan CoraccioJulianna Coraccio
http://compbio.dfci.harvard.edu