tranSMART Community Meeting 5-7 Nov 13 - Session 3: Pfizer’s Recent Use of tranSMART

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