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A Knowledge Model for Analysis and Simulation of Signal Transduction Networks

A Knowledge Model for Analysis and Simulation of Signal Transduction Networks. Our project is set up as a collaboration of three departments of Columbia University. Columbia Genome Center Computer Science Department of Medical Informatics. Authors:. Tomohiro Koike, Sergey Kalachikov,

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A Knowledge Model for Analysis and Simulation of Signal Transduction Networks

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

  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 thelogicalrepresentation 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 BA inactivates BA phoshorylates BA 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. biochemical logical

  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 Fujiwith no hurryIssa

  28. Thank you!

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