1. A Knowledge Model for Analysis and Simulation of Signal Transduction Networks

2. Our project is set up as a collaboration of three departments of Columbia University

3. Columbia Genome Center Computer Science Department of Medical Informatics

4. Authors: Tomohiro Koike, Sergey Kalachikov, Shawn M. Gomez, Michael Krauthammer, Sabina H. Kaplan, Pauline Kra, James J. Russo, Carol Friedman, Andrey Rzhetsky

5. Ontology: collection of concepts concept definitions relationships among concepts properties of each concept [explicit axioms]

6. Goal – a Particular Application Problem/Motivation: Currently a search through the PubMed system with the keywords “cell cycle” and “apoptosis” produced lists of 169,293 and 29,961 articles, respectively. Clearly it is not feasible to scan all these papers “manually”...

7. Outline of the system that we are designing

8. Basic concepts Action, ActionAgent, Process, Publication, Taxon, Disease, Mechanism, Result, Developmental Stage, MicroStructure, State, MacroStructure, Relation, Similarity, RelationType, and ActionTemplate

9. We represent a pathway a series of overlapping “links” – substance/action/substance triplets Substance A  Substance B  Substance C  Substance D Representation

10. ActionAgent

11. Action and Process

12. Auxiliary Concepts Publication, Taxon, Structure, Developmental Stage, and Disease encapsulate pieces of auxiliary information about ActionAgents, Processes and Actions

13. Properties of Concepts: ActionAgent

14. Properties of Concepts: Action

15. Duality of actions in signal transduction literature

16. Dualism: in the biochemical representation substance A is not a participant of the action, while it is in the logical representation Logical Biochemical

17. We realized that the current research literature in molecular biology Describes pathways on two different levels: Logical and Biochemical

18. A activates B A inactivates B A phoshorylates B A methylates B... logical biochemical

19. Both logical and biochemical descriptions can be combined in the same sentence: Activated raf-1 phosphorylates and activates mek-1. logical biochemical

20. Mechanism and Result of an Action

21. Mechanism and Result Result  LogicalAction Mechanism  BiochemicalAction

22. Converting LogicalAction into BiochemicalAction and back

23. The paper descibing this ontology will appear in Bioinformatics A. Rzhetsky, T. Koike, S. Kalachikov, S. M. Gomez, M. Krauthammer, S. H. Kaplan, P. Kra, J. J. Russo and C. Friedman, A knowledge model for analysis and simulation of regulatory networks, Bioinformatics, (accepted) (2000).

24. Implementation: A Pathway Editor Koike, T., and Rzhetsky, A. 2000. A graphic editor for analyzing signal transduction pathways. Gene (accepted).

25. Human cell cycle/apoptosis pathways

26. Small fragment of the same pathway

27. O snail, climb Mount Fuji with no hurry Issa

29. Thank you!