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© OCS Consulting EDA in Pharmacogenomics With SAS JMP and Windows WF.

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Presentation on theme: "© OCS Consulting EDA in Pharmacogenomics With SAS JMP and Windows WF."— Presentation transcript:

1 © OCS Consulting EDA in Pharmacogenomics With SAS JMP and Windows WF

2 © OCS Consulting Contents Introduction Hapmap, JMP and Windows WF Hapmap JMP Windows WF Application Next Steps Conclusions Questions

3 © OCS Consulting Introduction Dosing Models Model Comparison Modelling EDA Statistical Workflow of a Pharmacogenomic Study Warfarin Subgroup Analysis

4 © OCS Consulting Clinical Dosing Model Demographic Pharma Clinical From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764

5 © OCS Consulting Pharmacogenetic Dosing Model Demographic Genetic Pharma Clinical From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764

6 © OCS Consulting Model Comparison From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764

7 © OCS Consulting Model Comparison Workflow Impute Split Model Test Average 10 x Model Test Average 10 x Model Test Average 10 x Compare Select Validate X x A B

8 © OCS Consulting Statistical Workflow of a Pharmacogenomic Study 1 From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570

9 © OCS Consulting Modelling EDA Modelling / Comparisons: Routine Process WF compatible EDA : Investigative Process Smaller (routine) processes Model Extension Modelling + EDA WF possibility ?

10 © OCS Consulting Warfarin From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99- 111.

11 © OCS Consulting Warfarin 2 From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99- 111.

12 © OCS Consulting Statistical Workflow of a Pharmacogenomic Study 2 From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570

13 © OCS Consulting 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

14 © OCS Consulting Hapmap, JMP and WWF Hapmap JMP Hapmap JMP Workflow Windows WF Windows WF Activities Activities inside a State

15 © OCS Consulting Hapmap

16 © OCS Consulting Hapmap 2

17 © OCS Consulting JMP JMP Automation JMP Script JMP Workflow Builder

18 © OCS Consulting JMP 2

19 © OCS Consulting Hapmap JMP Workflow

20 © OCS Consulting Windows WF

21 © OCS Consulting Windows WF Activities

22 © OCS Consulting Activities inside a State

23 © OCS Consulting Start JMP Script in Activity

24 © OCS Consulting Hapmap JMP WWF Application User Input for State Events User Input for JMP Script JMP Report VKORC1 Marker rs9923231 JMP Script Results

25 © OCS Consulting Hapmap JMP WWF Application 2

26 © OCS Consulting User Input for State Events

27 © OCS Consulting User Input for JMP Script

28 © OCS Consulting JMP Report

29 © OCS Consulting VKORC1 Marker rs9923231

30 © OCS Consulting Results Restriction using Chi-Square Test

31 © OCS Consulting JMP Script Results

32 © OCS Consulting Next Steps Different Model factors Different Modelling Techniques Taverna Workflow Warfarin History WWF Custom Activity Tracking Persistence Error Handling Workflow Re-use / Validation

33 © OCS Consulting Different Model Factors

34 © OCS Consulting VKORC1 Marker rs9923231 Clin1 Clin2 Clin3 Pharm1 Pharm2 Pharm3 Ethnic Pharma Clinical

35 © OCS Consulting Different Modelling Techniques

36 © OCS Consulting Detecting and Controlling for Population Stratification From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570

37 © OCS Consulting Taverna Workflow Open Source Beanshell Scripts Rshell Scripts (On – off) Data Flow UI Command Line App From http:\\taverna.sourceforge.net

38 © OCS Consulting Warfarin History Anti-clotting Agent high responders low responders Rodenticide resistance Rare Familial Diseases coagulation factor deficiencies

39 © OCS Consulting Compare Genes of Species or Families

40 © OCS Consulting WWF Custom Activity

41 © OCS Consulting Tracking State 1 State 2 State 3 State 4 …

42 © OCS Consulting Tracking2 From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.

43 © OCS Consulting Persistence From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.

44 © OCS Consulting Persistence 2

45 © OCS Consulting Error Handling

46 © OCS Consulting Workflow Re-use / Validation From http:\\taverna.sourceforge.net

47 © OCS Consulting Workflow Validation 2 Validate Stop Workflow

48 © OCS Consulting Error Handling 2 FTP Unzip Reconnect

49 © OCS Consulting Hapmap JMP WWF Application3

50 © OCS Consulting 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.

51 © OCS Consulting Questions ?


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