This is a presentation I gave at the San Diego Bioinformatics Forum on October of 2006.

1. New approaches to elucidating Structure Activity Relationships Chris Petersen Technical Manager, Informatics

5. How do users need this information displayed? structures activity SAR table

6. But how is the data for the SAR table selected? structures activity SAR table

14. Chemoprints aggregate the activities of compounds Target Chemoprint Compound Rosiglitazone (Avandia) activity (efficacy +/- SD) targets (cellular and biochemical)

15. Our database structure enables useful aggregation Experiments are instances of a protocol and all protocols have a defined target All data is generated for a compound in an experiment Each compound gets one number for efficacy and one for potency Target Experiment Protocol

16. Chemoprints aggregate the activities of compounds Target Chemoprint Compound Rosiglitazone (Avandia) activity (efficacy +/- SD) targets (cellular and biochemical)

18. Chemoprints aggregate the activities of compounds by target activity (efficacy +/- SD) targets Target Chemoprint Compound Rosiglitazone (Avandia) PPAR  (cellular and biochemical)

21. Target Chemoprints allow biologists to access compound activities in individual experiments activity (efficacy +/- SD) targets EGR1 (cellular assays) PPAR  (cellular and biochemical) Target Chemoprint Compound Rosiglitazone (Avandia)

23. Protocol Chemoprints allow users to access data of active structural elements Protocol Chemoprint activity (efficacy +/- SD) experimental protocols Target Chemoprint Compound Rosiglitazone (Avandia) view off-target activities

24. Protocol Chemoprints display data of active structural elements Protocol Detail structural elements (scaffolds) Protocol Chemoprint Target Chemoprint Compound Rosiglitazone (Avandia) view off-target activities view by experiments activity

28. We use HierS scaffold analysis algorithm to classify structural elements in the database 1. identify ring systems ring systems share internal bonds

35. We use HierS scaffold analysis algorithm to classify structural elements in the database Scaffold Detail structural elements (scaffolds) Protocol Detail

36. Scaffolds identified by HierS allow navigation to activity information Structure Detail structural elements (scaffolds) Scaffold Detail

37. Scaffolds identified by HierS allow navigation to activity information Scaffold Detail Structure Detail view by scaffold structural elements (scaffolds) activity

38. Scaffold Target chemoprints show aggregate data for all compounds that contain scaffold view by activity Scaffold Detail Structure Detail view by scaffold Scaffold Chemoprint aggregate activity data for 34 compounds containing this scaffold

39. Scaffold Target chemoprints can highlight activity intrinsic to a scaffold view by activity Scaffold Detail Structure Detail view by scaffold Scaffold Chemoprint aggregate activity data for 34 compounds containing this scaffold Activity not tightly tied to scaffold

40. Scaffold Target chemoprints can highlight activity intrinsic to a scaffold view by activity Scaffold Detail Structure Detail view by scaffold Scaffold Chemoprint Activity not tightly tied to scaffold aggregate activity data for 34 compounds containing this scaffold Activity very tightly tied to scaffold

41. Summary Chemoprints provide a way for Biologists to visualize massive amounts of biological data to discover what compounds are active against a target HierS scaffolds provide a means for Chemists to discover what structural features are related to activity and to find distinct scaffold that exhibit that activity