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 Cdk CycB Cdh1 CKI Cln Cdk Cdc20 +APC Molecular network +APC Differential equations

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

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 Ma->Mi Mi->Ma Reaction Equations

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 activationMPF 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