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tranSMART Community Meeting 5-7 Nov 13 - Session 3: Pfizer’s Recent Use of tranSMART Sizeable Neuroscience Studies (ADNI, PPMI, TBI), Completing a Large Scale GWAS Initiative and a View Towards Individual Genomes Jay Bergeron, Pfizer Over the past months, Pfizer has expanded the tranSMART footprint to include the Neuroscience Research Unit by incorporating three substantial longitudinal studies associated with Alzheimer’s, Parkinson’s and Traumatic Brain Injury. These represent the most complicated translational studies that Pfizer has incorporated to date. Additionally, the company has completed the loading of 300 GWAS sets associated with multiple indications, enhanced error checking while loading GWAS and is preparing for large scale Genomics data in 2014.
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tranSMART and Pfizer
GWAS, Exploratory Research and Preparing for Large Scale Genotyping
Jay BergeronDirector, Translational and BioinformaticsPfizer inc.Cambridge Mass
Co-Lead, Platform DevelopmenteTRIKS
tranSMART HackathonParis – Nov 5-7 2013
Oct 07-08, 2013, Berlin, Germany
Exploratory Use
Submission Use
Specialty systems Gene
Expression Systems
Biology Other
Operational reporting
CRO1
CRO2
CRO …
Clinical data analysis
1
ClinicalTrials
Management
Public data
Molecular datafrom PFE studies
Downstream Systems Medical Safety Regulatory PharmSci ClinPharm Portfolio Finance Documents …
Exploratory Analysis
2
1 Exchange of clinical or moleculardata as needed
2 Feed specialty analysis systems and retrieve results
Clinical/Translational Data Flow
Phase 32300
Phase 32300
NeuroPPMINeuroPPMI
Inf&RegInf&Reg
CVMEDCVMED
NeuroADNINeuroADNI
>150 Case Control12 eQTL Loaded
>300 Metabolomic QTL
>150 Case Control12 eQTL Loaded
>300 Metabolomic QTL>300 Case Control>300 Case Control
BioTxBioTx PharmaTxPharmaTx
CollectionCollection
ImmunoImmuno
GWAVAGWAVA
BioBankBioBank
ImmunoImmuno
CVMEDCVMED
OncologyOncology
ClinicalClinical
PipelinesPipelines
ExpressionExpression
Translational Studies
GWAS
Genotypes
Trials-Exploratory
AIBL?
CAMD?
NEXTNEXT
NEXTNEXT
NEXTNEXTMoreGenotypes
Pfizer’s Use of tranSMART
VaccinesVaccines
NeuroTRACKNeuroTRACK
Timeline
Agenda
GWAS Support for Exploratory Data Types Large Scale Collaborations
ADNIPPMITRACK
Analytical SupportGenedata Expressionist
Genome Wide Association Studies
Contribution: GWAS
GWAS search enabled in tranSMART using the Faceted Search component with filtering by study, analysis and region of interest
GWAS-Specific User Data Load Form
GWAS Search Upload
Query Across GWAS Analyses
Search of Region of Interest
Interactive Manhattan PlotsGWAVA
Java Web StartThick Client
-Search Analyses by Genes/RS IDs-Generate Manhattan Plots
Overlays and TrellisesPresentation Ready
-Generate Tabular Results
Access via the BioservicesPlatform (eQTL/mQTL)
A supplement to the tranSMART user interface where necessary
GWASData Verification and Correction
CorrectionGWAS files can be mapped to specific field namesChecked for errors prior to loading
Records having errors can be removed
GWAS
~500 GWAS Analyses to Date 12 EQTL, 1 MQTL ~700GB
GWAS: Second Development Effort Plug-in Architecture GWAS Filter Enhancements Full integration of GWAVA Document Representation Saved Searches (Dataset Explorer)
Commitment to Open Source Recombinant and the Hyve
Large Scale Queries Considering MPPs
In general we could argue that nearly all of the projects/targets that we review benefit from tranSMART/GWAVA because the tools allow us to quickly review targets for a broad range of phenotypic associations. In some cases we find additional associations, in some cases we do not. The ability to do this quickly and efficiently is important.- Geneticist, Precision Medicine
2300 GenotypesFrom a
Phase-3 Study
Genotypes
Genotypes: Access via the R-API and Bioservices
Access via the R-Serve Interface
Currently Accessed via a Bio Service
10’s of thousands additional genotypes expected in 2014
Pfizer BT* Christoph Brockel Angela Gaudette Peter Henstock Ami Khandeshi Michael Miller Anna Silberberg Kurt Watrous Haiyan Zhang Rohit Ranjan
GWAS Contributors
Pfizer RUs* Eric Fauman Janna Hutz Scott Jelinsky Katrina Loomis Sara Paciga Craig Hyde Matt Pletcher Nadeem Sarwar Ciara Vangjeli Gemma Wilk Li Xi
Recombinant* Dina Aronzon Bob Coopersmith John Gagnon Devon Johnson Jinlei Liu Michael McDuffie David Newton Nancy Pickard Raveen Sharma Chris Urich Haiping Xia
*BT: Business Technologies *RU: Research Unit *Recombinant: Recombinant by Deloitte
Exploratory Molecular Data Support
Support for Metabolomics
Metabolomics
Support for Protein Assays
Protein Assays
Support for FACS
FACS
Exploratory Molecular Data
Predominantly Low Dimensional Representation Possibly dual (High and Low) representation Clearly exposes data set explorer export limitations
Most Exploratory Data Loading Performed in House Haiyan Zhang
All Pfizer ETL Engineering Ami Khandeshi
Large Scale Collaborative Efforts
Use case: ADNI and PPMI data in tranSMARTEnabling rapid exploratory analyses and hypothesis generation
• Data obtained from consortia and collaborations are often poorly utilized and have limited distribution across Pfizer
• Isolated, local storage of datasets
• Multiple, incomplete versions
• Duplication of efforts to transform data
• Two large Neuroscience datasets were chosen for addition to tranSMART
• Further evaluate the utility of tranSMART for exploratory data analysis by researchers
• Permit the development of processes for data importation and handling
• Establish tranSMART training processes
ADNI and PPMI in tranSMART
Enabling rapid exploratory analyses and hypothesis generation
Overview ADNI Datasets in tranSMART
LONI Data Download
Approximately 140 excelspreadsheets
2972 subjects
~8,000,000 data points
ADNI Dataset
8,000,000 Data Points
Overview PPMI Datasets in tranSMART
LONI data download
approximately 75 excel
Spreadsheets780 subjects~715,000 datapoints
PPMI Data Set
~715,000 Data Points
24
Overview PPMI Datasets in tranSMARTWhat were the ADAS-Cog11 scores at screening?
Drag and drop Numerical Data from the Study Navigation to Results/Analysis tab to Get t-test statistics
NL AD
Overview PPMI Datasets in tranSMARTWhat are the baseline demographics of Healthy and AD subjects in ADNI1?
NL AD
Overview PPMI Datasets in tranSMARTWhat were the Base Assessment Scores
for the Healthy Control vs AD cohorts?
NL AD
Overview PPMI Datasets in tranSMARTAre There Differences in
CSF Biomarkers at Baseline?
HDD Priority: Limited use of clinical data obtained externally
TRACK-TBIImpact of Consistent Systems
One Mind for Research uses tranSMARTPfizer Obtained these Data Overnight Once the Agreement was In Place
One Mind for Research uses tranSMARTPfizer Obtained these Data Overnight Once the Agreement was In Place
Neuroscience Collaborative StudiesADNI, PPMI, TRACK
tranSMART: standard data aggregator for Prec. Med.
ADNI , PPMI, TRACK datasets imported
Initial training of end users
Follow-up will be performed over the next 3 months
All new collaboration and consortia proposals need to include
Downstream data use, analysis and management
Including budget/resources
Availability of data in tranSMART allows exploratory analysis of the large datasets in minutes rather than days or weeks – Director, Neuroinformatics
Availability of data in tranSMART allows exploratory analysis of the large datasets in minutes rather than days or weeks – Director, Neuroinformatics
tranSMART
HDD Priority: Limited use of clinical data obtained externally
Data Management and Collaborations
Pfizer BT* Ami Khandeshi Anna Silberberg Haiyan Zhang Robb Linde
Contributors
Pfizer RUs* Tom Comery Jesse Macomber Peter Bergethon
*BT: Business Technologies *RU: Research Unit
Thomson Reuters Sirimon Ocharoen Ray Wright
IDBS Mark Dekanter Donnie Qi Matt Clifford Vladimir Kubatin
One Mind for Research Srini K Magali Haas
Analytical Integration
HDD Priority: Limited use of clinical data obtained externally
A button added to the advanced workflow for transferring data from tranSMART to Genedata Analyst
Genedata/tranSMART Integration
HDD Priority: Limited use of clinical data obtained externally
Genedata/tranSMART Integration
A button added to Genedata analyst for transferringclinical data from tranSMART
HDD Priority: Limited use of clinical data obtained externally
Example of a PCA of data transferred from tranSMART
Genedata/tranSMART Integration
Pfizer BT* Angela Gaudette Peter Henstock Andrew Hill Ami Khandeshi Anna Silberberg Haiyan Zhang Bill Mounts Scott Jelinsky
ContributorsExpressionist Integration
*BT: Business Technologies *RU: Research Unit *Recombinant: Recombinant by Deloitte
Genedata Daniel Nesbit Alice Li James Cooper Jens Hoefkens Jessica Qi Michael Riegelhaupt Scott Faria
HDD Priority: Limited use of clinical data obtained externally
Final Thoughts
Plans GWAS in 1.2 Genotypes Analytical Integration
Collaborative tranSMART Foundation eTRIKS others?
Outreach Helping commercial entities find value in the tranSMART community
Pfizer BT* Christoph Brockel Angela Gaudette Peter Henstock Andrew Hill Ami Khandeshi David Klatte Michael Miller Anna Silberberg Padma Reddy Kurt Watrous Haiyan Zhang Anita Pracheta Rohit Ranjan
Contributors
Pfizer RUs* Eric Fauman Scott Jelinsky Katrina Loomis Sara Paciga Stephanie Hall Craig Hyde Nadeem Sarwar Michael Swietek Ciara Vangjeli Li Xi Tom Comery Jesse Macomber
Recombinant* Dina Aronzon Jinlei Liu Michael McDuffie David Newton Nancy Pickard Raveen Sharma Haiping Xia John Gagnon
*BT: Business Technologies *RU: Research Unit *Recombinant: Recombinant by Deloitte
Thomson Reuters Sirimon Ocharoen Ray Wright
IDBS Mark Dekanter Donnie Qi Matt Clifford Vladimir Kubatin
Genedata Daniel Nesbit Alice Li James Cooper Jens Hoefkens Jessica Qi Michael Riegelhaupt Scott Faria