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Curation of models: Painstaking effort or rewarding activity?

Curation of models: Painstaking effort or rewarding activity?. Harish Dharuri Monday, October 20, 2014 Second Biomodels.net Training Camp. What makes it painstaking…. Incomplete information in the paper Missing Initial Conditions Parameter values

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Curation of models: Painstaking effort or rewarding activity?

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  1. Curation of models: Painstaking effort or rewarding activity? Harish Dharuri Monday, October 20, 2014 Second Biomodels.net Training Camp

  2. What makes it painstaking… • Incomplete information in the paper • Missing • Initial Conditions • Parameter values • Lack of correspondence between simulation result and figures given in the paper. • Typo’s in model equations or just outright wrong representation. • Unresponsive authors.

  3. What makes it painstaking… • Software issues: SBML compliance. • Balance the need to make models compatible across the spectrum with aesthetics of model representation.

  4. What makes it rewarding…and there are many reasons • Learning • Learning • Learning

  5. Examples in Model Integration • Yeast Pheromone Pathway and Cell Cycle • BIOMD0000000032 and BIOMD0000000056 • Calcium Dynamics

  6. Yeast Pheromone Pathway CDC28+Far1PP: Leads to Cell Cycle Arrest

  7. Far1PP-CDC28 time profile

  8. Budding Yeast Cell Cycle, Chen et al (2004)

  9. Time Series – Cell Cycle Model

  10. Kegg Pathway

  11. CLN1,2,3 Mutant – G1 Arrest

  12. Recap • What we are doing… • Merging the Yeast Pheromone model and the Cell cycle model. • Far1PP-CDC28 (ComplexN) inhibits Cyclins (CLN1, CLN2 and CLN3) in the cell cycle model. • Inference made from literature. • What we hope to see… • Cell cycle stop in the G1 phase. • Needs to look like experimental data from CLN (1,2,3) mutants.

  13. Introduction of Pheromone mating factor Dynamics of the Merged Model - DNA synthesis

  14. Introduction of Pheromone mating factor Dynamics of the Merged Model – CKI profile

  15. Calcium signaling pathway

  16. Conclusions • What makes it painstaking • Issues with • Publications • Software • Authors don’t like me  • What makes it rewarding • Offers a terrific learning experience • Ideal training for a Systems Biology aspirant

  17. Conclusions • Another Issue • Employability with this skill set • What is the market demand/perception

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