The document summarizes Pfizer's use of the tranSMART platform for various genomics and clinical data analyses including genome-wide association studies (GWAS), supporting exploratory data types like metabolomics and FACS data, and large collaborative efforts like the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Parkinson's Progression Markers Initiative (PPMI) datasets. It also discusses analytical integration with Genedata Expressionist and plans for future enhancements to tranSMART like improved GWAS support and additional genotype data. Contributors to these efforts are acknowledged.

1. tranSMART Hackathon
Paris – Nov 5-7 2013
tranSMART and Pfizer
GWAS, Exploratory Research and Preparing for Large Scale
Genotyping
Jay Bergeron
Director, Translational and
Bioinformatics
Pfizer inc.
Cambridge Mass
Co-Lead, Platform Development
eTRIKS
Oct 07-08, 2013, Berlin, Germany

2. Clinical/Translational Data Flow
CRO1
Downstream Systems
 Medical
 Safety
 Regulatory
 PharmSci
 ClinPharm
 Portfolio
 Finance
 Documents
 …
Clinical
Trials
Management
CRO2
CRO …
1
Operational
reporting
Clinical data
analysis
Submission Use
2
Public data
Molecular data
from PFE studies
1
Exchange of clinical or molecular
data as needed
2
Feed specialty analysis systems
and retrieve results
Exploratory
Analysis
Specialty systems
 Gene
Expression
 Systems
Biology
 Other
Exploratory Use

3. Pfizer’s Use of tranSMART
Translational Studies
Vaccines
Vaccines
Neuro
Neuro
PPMI
PPMI
Neuro
Neuro
TRACK
TRACK
Immuno
Immuno
Neuro
Neuro
ADNI
ADNI
Inf&Reg
Inf&Reg
NEXT AIBL?
NEXT
NEXT CAMD?
NEXT
CVMED
CVMED
Genotypes
Immuno
Immuno
Phase 33
Phase
2300
2300
BioBank
BioBank
Clinical
Clinical
Pipelines
Pipelines
Collection
Collection
CVMED
CVMED
Expression
Expression
More
NEXT
NEXT Genotypes
GWAVA
GWAVA
>150 Case Control
>150 Case Control
12 eQTL Loaded
12 eQTL Loaded
>300 Metabolomic QTL
>300 Metabolomic QTL
GWAS
BioTx
BioTx
>300 Case Control
>300 Case Control
PharmaTx
PharmaTx
Oncology
Oncology
Trials-Exploratory

4. Timeline

5. Agenda
 GWAS
 Support for Exploratory Data Types
 Large Scale Collaborations
ADNI
PPMI
TRACK
 Analytical Support
Genedata Expressionist

6. Genome Wide Association Studies

7. Contribution: GWAS
GWAS search enabled in tranSMART using the Faceted Search
component with filtering by study, analysis and region of interest

8. GWAS Search Upload
Query Across GWAS Analyses
Search of Region of Interest
GWAS-Specific User Data Load Form

9. Interactive Manhattan Plots
GWAVA
Java Web Start
Thick Client
-Search Analyses by Genes/RS IDs
-Generate Manhattan Plots
Overlays and Trellises
Presentation Ready
-Generate Tabular Results

10. Access via the Bioservices
Platform (eQTL/mQTL)
A supplement to the tranSMART
user interface where necessary

11. GWAS
Data Verification and Correction
Correction
GWAS files can be mapped to specific field names
Checked for errors prior to loading
Records having errors can be removed

12. GWAS
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
 ~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

13. Genotypes
Genotypes: Access via the R-API and Bioservices
2300 Genotypes
From a
Phase-3 Study
Access via the R-Serve Interface
Currently Accessed via a Bio Service
10’s of thousands additional genotypes
expected in 2014

14. GWAS Contributors
 Pfizer BT*









Christoph Brockel
Angela Gaudette
Peter Henstock
Ami Khandeshi
Michael Miller
Anna Silberberg
Kurt Watrous
Haiyan Zhang
Rohit Ranjan
*BT: Business Technologies
Pfizer RUs*
 Eric Fauman
 Janna Hutz
 Scott Jelinsky
 Katrina Loomis
 Sara Paciga
 Craig Hyde
 Matt Pletcher
 Nadeem Sarwar
 Ciara Vangjeli
 Gemma Wilk
 Li Xi
*RU: Research Unit
 Recombinant*
 Dina Aronzon
 Bob Coopersmith
 John Gagnon
 Devon Johnson
 Jinlei Liu
 Michael McDuffie
 David Newton
 Nancy Pickard
 Raveen Sharma
 Chris Urich
 Haiping Xia
*Recombinant: Recombinant by Deloitte

15. Exploratory Molecular Data Support

16. Support for Metabolomics
Metabolomics

17. Support for Protein Assays
Protein Assays

18. Support for FACS
FACS

19. 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

20. Large Scale Collaborative Efforts

21. Use case: ADNI and PPMI data in and PPMI in tranSMART
ADNI tranSMART
Enabling rapid exploratory analyses and hypothesis generation
Enabling 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

22. Overview ADNI Datasets in tranSMART
8,000,000 Data Points
LONI Data Download
Approximately 140 excel
spreadsheets
2972 subjects
~8,000,000 data points
ADNI Dataset

23. Overview PPMI Datasets in tranSMART
~715,000 Data Points
LONI data
download
approximately 75
excel
Spreadsheets
780 subjects
~715,000 datapoints
PPMI Data Set

24. What were the ADAS-Cog11 scores at
Overview PPMI Datasets in tranSMART
screening?
Drag and drop Numerical Data from the Study
Navigation to Results/Analysis tab to Get t-test statistics
24

25. What tranSMART
Overview PPMI Datasets in are the baseline demographics of
Healthy and AD subjects in ADNI1?
NL
AD

26. What were the Base Assessment Scores
Overview PPMI Datasets inthe Healthy Control vs AD cohorts?
for tranSMART
NL
AD

27. Are There Differences in
Overview PPMI Datasets in tranSMART
CSF Biomarkers at Baseline?
NL
AD

28. TRACK-TBI
HDD Priority:
Impact of Consistent Systems
Limited use of clinical data obtained externally
One Mind for Research uses tranSMART
One Mind for Research uses tranSMART
Pfizer Obtained these Data Overnight Once the Agreement was In Place
Pfizer Obtained these Data Overnight Once the Agreement was In Place

29. Neuroscience Collaborative Studies
HDD Priority:Data Management and Collaborations
ADNI, PPMI, TRACK of clinical data obtained externally
Limited use
Availability of data in tranSMART allows exploratory analysis of the large datasets in minutes rather than
Availability of data in tranSMART allows exploratory analysis of the large datasets in minutes rather than
days or weeks – Director, Neuroinformatics
days or weeks – Director, Neuroinformatics
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

30. Contributors
 Pfizer BT*




Ami Khandeshi
Anna Silberberg
Haiyan Zhang
Robb Linde
Pfizer RUs*
 Tom Comery
 Jesse Macomber
 Peter Bergethon
*BT: Business Technologies
Thomson Reuters
 Sirimon Ocharoen
 Ray Wright
IDBS
 Mark Dekanter
 Donnie Qi
 Matt Clifford
 Vladimir Kubatin
 One Mind for Research
 Srini K
 Magali Haas
*RU: Research Unit

31. Analytical Integration

32. HDD Priority:
Genedata/tranSMART Integration
Limited use of clinical data obtained externally
A button added to the advanced workflow for transferring data from
tranSMART to Genedata Analyst

33. HDD Priority:
Genedata/tranSMART Integration
Limited use of clinical data obtained externally
A button added to Genedata analyst for transferring
clinical data from tranSMART

34. HDD Priority:
Genedata/tranSMART Integration
Limited use of clinical data obtained externally
Example of a PCA of data transferred from tranSMART

35. Contributors
Expressionist Integration
 Pfizer BT*








*BT: Business Technologies
Genedata
Angela Gaudette
Peter Henstock
Andrew Hill
Ami Khandeshi
Anna Silberberg
Haiyan Zhang
Bill Mounts
Scott Jelinsky
*RU: Research Unit
 Daniel Nesbit
 Alice Li
 James Cooper
 Jens Hoefkens
 Jessica Qi
 Michael Riegelhaupt
 Scott Faria
*Recombinant: Recombinant by Deloitte

36. HDD Priority:
Final Thoughts
Limited use of clinical data obtained externally
 Plans
 GWAS in 1.2
 Genotypes
 Analytical Integration
 Collaborative
 tranSMART Foundation
 eTRIKS
 others?
 Outreach
 Helping commercial entities find value in the
tranSMART community

37. Contributors
 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
Thomson Reuters
 Sirimon Ocharoen
 Ray Wright
*BT: Business Technologies
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
IDBS
 Mark Dekanter
 Donnie Qi
 Matt Clifford
 Vladimir Kubatin
*RU: Research Unit
 Recombinant*
 Dina Aronzon
 Jinlei Liu
 Michael McDuffie
 David Newton
 Nancy Pickard
 Raveen Sharma
 Haiping Xia
 John Gagnon
Genedata
 Daniel Nesbit
 Alice Li
 James Cooper
 Jens Hoefkens
 Jessica Qi
 Michael
Riegelhaupt
 Scott Faria
*Recombinant: Recombinant by Deloitte