Transcript presentation

EDA in Pharmacogenomics
With
SAS JMP and Windows WF
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Contents
Introduction
Hapmap, JMP and Windows WF
Hapmap JMP Windows WF Application
Next Steps
Conclusions
Questions
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Introduction
Dosing Models
Model Comparison
Modelling  EDA
Statistical Workflow of a
Pharmacogenomic Study
Warfarin
Subgroup Analysis
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Clinical Dosing Model
Demographic
Pharma
Clinical
From The International Warfarin Pharmacogenetics Consortium. N Engl
J Med 2009;360(8):753-764
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Pharmacogenetic Dosing Model
Demographic
Genetic
Pharma
Clinical
From The International Warfarin Pharmacogenetics Consortium. N Engl
J Med 2009;360(8):753-764
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Model Comparison
From The International Warfarin Pharmacogenetics Consortium. N Engl
J Med 2009;360(8):753-764
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Model Comparison Workflow
Impute
Split
Split
Model
Model
Xx
10 x
Test
Average
A
Test
10 x
Average
B
Compare
Select
Model
Test
10 x
Average
Validate
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Statistical Workflow of a
Pharmacogenomic Study 1
From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol
2009;2(5):559-570
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Modelling  EDA
Modelling / Comparisons: Routine
Process
• WF compatible
EDA : Investigative Process
• Smaller (routine) processes
Model Extension
• Modelling + EDA
• WF possibility ?
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Warfarin
From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99111.
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Warfarin 2
From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99111.
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Statistical Workflow of a
Pharmacogenomic Study 2
From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol
2009;2(5):559-570
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Subgroup Analysis
Presumable more unknown factors are involved
that are distributed differently in different
populations, e.g. dietary habits.
Given this state of knowledge the question
remains whether to use one universal dosing
algorithm or to use different dosing
algorithms for different subpopulations.
This subgroup analysis could be extended to
other model factors
• clinical (diseases / disease states)
• pharma (high responder / low responder)
Test
Test
Test
Test
Test
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Hapmap, JMP and WWF
Hapmap
JMP
Hapmap JMP Workflow
Windows WF
Windows WF Activities
Activities inside a State
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Hapmap
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Hapmap 2
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JMP
JMP Automation
JMP Script
JMP Workflow Builder
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JMP 2
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Hapmap JMP Workflow
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Windows WF
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Windows WF Activities
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Activities inside a State
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Start JMP Script in Activity
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Hapmap JMP WWF Application
User Input for State Events
User Input for JMP Script
JMP Report
VKORC1 Marker rs9923231
JMP Script Results
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Hapmap JMP WWF Application 2
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User Input for State Events
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User Input for JMP Script
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JMP Report
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VKORC1 Marker rs9923231
refhom-count
het-count
otherhom-count
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Results Restriction using Chi-Square Test
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JMP Script Results
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Next Steps
Different Model factors
Different Modelling Techniques
Taverna Workflow
Warfarin History
WWF Custom Activity
Tracking
Persistence
Error Handling
Workflow Re-use / Validation
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Different Model Factors
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VKORC1 Marker rs9923231
Ethnic
Clin1
Clin2
Clin3
Pharm1
Pharm2
Pharm3
Clinical
Pharma
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Different Modelling Techniques
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Detecting and Controlling for Population
Stratification
From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol
2009;2(5):559-570
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Taverna Workflow
Open Source
Beanshell Scripts
Rshell Scripts
(On – off) Data Flow
“UI”
Command Line App
From http:\\taverna.sourceforge.net
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Warfarin History
Anti-clotting Agent
•  high responders
•  low responders
Rodenticide
•  resistance
Rare Familial Diseases
•  coagulation factor deficiencies
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Compare Genes of Species or Families
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WWF Custom Activity
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Tracking
State
State
State
State
…
1
2
3
4
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Tracking2
From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.
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Persistence
From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.
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Persistence 2
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Error Handling
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Workflow Re-use / Validation
From http:\\taverna.sourceforge.net
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Workflow Validation 2
Validate
Stop
Workflow
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Error Handling 2
FTP
Unzip
Reconnect
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Hapmap JMP WWF Application3
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Conclusions
It is possible to combine a data fetch and
JMP scripts in a Windows workflow.
The graphical designer is attractive but
not a Lego-like activity.
With more elaborate modelling or EDA
workflows, the Tracking, Persistence
and Error handling features probably
make it worth considering.
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Questions
?
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