The JigCell Problem Solving Environment (PSE)

1. The JigCell Problem Solving Environment (PSE) Marc Vass and Nick Allen Department of Computer Science Virginia Tech

2. Computational Molecular Biology • Conversions are done by hand CKI +APC Cdh1 +APC Cdk Cdc20 Cln Cdk CycB Molecular network Differential equations

3. Pds1 Esp1 Sic1 Sic1 P Esp1 Sister chromatid separation unaligned chromosomes SBF Cdh1 Pds1 Mcm1 Cdc20 PPX Net1P Tem1-GDP Cdc15/MEN Lte1 Bub2 Tem1-GTP Net1 Cdc14 Mcm1 Cdh1 Cdc20 RENT Cln2 Clb2 Clb5 Mad2 growth IEP unaligned chromosomes Mcm1 Cdc20 Cdh1 APC Clb2 Inactive trimer Cdc14 and Cln3 Swi5 CDKs SCF P Cdc14 Bck2 Inactive trimer ? MBF Clb5 DNA synthesis Clb2 SBF Cln2 Budding

4. The JigCell PSE • Why we need a PSE • Representing a model • Making a prediction based on the model • Validating a model

5. Without a PSE • Impossible to move beyond simple hand built models • Evaluating models is repetitive and time consuming • Leads to more errors

6. Begin with a Wiring Diagram Frog Egg Extract Model Reaction Equations Ma->Mi Mi->Ma

7. Enter Wiring Diagram into Model Builder

8. Define Parameters and Initial Conditions

9. Performing a Comparison • Identify experimental results of interest • Define a simulation with equivalent conditions • Massage simulation results into a usable form • Run an objective evaluation

10. Define Experimental Data

11. Associate Experimental Data with a Model

12. Massage Simulation Results

13. Define Objective Evaluation

14. Compare Simulations to Experiments • Quick identification of problems

15. Visualize Results MPF mphase activation MPF interphase activation

16. Conclusions • JigCell allows modelers to produce truly useful computer representations of molecular regulatory systems • JigCell also allows modelers to quickly evaluate and re-evaluate changes to their models against experimental data

17. Questions