The JigCell Problem Solving Environment (PSE)

Marc Vass and Nick AllenDepartment of Computer Science

Virginia Tech

Computational Molecular Biology

Conversions are done by hand

CdkCycB

Cdh1 CK

I

ClnCdk

Cdc20 +APC

Molecular network

+APCd CDK

dt = k1 - (v2’ + v2” . Cdh1 ) . CDK

d Cdh1dt =

(k3’ + k3” . Cdc20A) (1 - Cdh1) J3 + 1 - Cdh1 -

(k4’ + k4” . CDK . M) Cdh1 J4 + Cdh1

d IEPdt = k9

. CDK . M . (1 – IEP ) – k10 . IEP

d Cdc20T

dt = k5’ + k5” (CDK . M)4

J54 + (CDK . M)4 - k6

. Cdc20T

d Cdc20A

dt = k7

. IEP (Cdc20T - Cdc20A) J7 + Cdc20T - Cdc20A

- k8

. MAD Cdc20A

J8 + Cdc20A - k6

. Cdc20T

Differential equations

growth

RENT

Lte1

Clb5MBF

P Sic1 SCFSic1Swi5

Clb2Mcm1

APC

Cdc14

Cdc14

CDKs

Cln2SBF

?

andCln3

Bck2

DNA synthesis

Inactive trimer

Inactive trimer

P

Clb2

Budding

Cdc20

Cdc20

Cdh1

Cdh1

Mcm1

Mad2

unaligned chromosomes

Cdc14

SBF

Esp1 Esp1Pds1

Pds1

Net1

Net1P

PPX

Cdc15/MENTem1-GDP

Tem1-GTPBub2

unaligned chromosomesCdh1

Sister chromatid separation

Mcm1

IEP

Cln2Clb2Clb5

Cdc20

The JigCell PSE

Why we need a PSE Representing a model Making a prediction based on the

model Validating a model

Without a PSE

Impossible to move beyond simple hand built models

Evaluating models is repetitive and time consuming

Leads to more errors

Begin with a Wiring Diagram

Frog Egg Extract Model

Ma->MiMi->Ma

Reaction Equations

Enter Wiring Diagram into Model Builder

Define Parameters and Initial Conditions

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

Define Experimental Data

Associate Experimental Data with a Model

Massage Simulation Results

Define Objective Evaluation

Compare Simulations to Experiments

Quick identification of problems

Visualize Results

MPF mphase activation MPF interphase activation

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

Questions