Transcript The JigCell Problem Solving Environment (PSE) Marc Vass and Nick Allen

The JigCell Problem Solving
Environment (PSE)
Marc Vass and Nick Allen
Department of Computer Science
Virginia Tech
CKI
Computational Molecular
Biology
d CDK
= k1 - (v2’ + v2” . Cdh1 ) . CDK
dt
d Cdh1 (k3’ + k3” . Cdc20A) (1 - Cdh1) (k4’ + k4” . CDK . M) Cdh1
=
dt
J3 + 1 - Cdh1
J4 + Cdh1
Cdk
Cln
d IEP
= k9 . CDK . M . (1 – IEP ) – k10 . IEP
dt
d Cdc20T
(CDK . M)4
= k5’ + k5 ” 4
- k6 . Cdc20T
dt
J5 + (CDK . M)4
Cdk
CycB
Molecular network

d Cdc20A k7 . IEP (Cdc20T - Cdc20A) k8 . MAD Cdc20A
=
- k6 . Cdc20T
dt
J7 + Cdc20T - Cdc20A
J8 + Cdc20A
Differential equations
Conversions are done by hand
Esp1
Pds1
Esp1
Sister chromatid separation
unaligned chromosomes
Cdh1
SBF
Pds1
Mcm1
Cdc20
PPX
Net1P
Tem1-GDP
Cdc15/MEN
Lte1
Bub2
Tem1-GTP
Net1
Mcm1
Cdc14
Cdh1
Cdc20
RENT
Mad2
growth
IEP
Mcm1
Clb2
Cln3
Cln2
Clb2
Swi5
and
Cdc20
APC
Inactive trimer
Cdc14
Sic1
Bck2
CDKs
PP
Sic1
Cdc14
Inactive trimer
?
MBF
Clb5
DNA synthesis
Clb2
SBF
Clb5
unaligned chromosomes
Cln2
Budding
SCF
Cdh1
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
Reaction Equations
Ma->Mi
Mi->Ma
Frog Egg Extract Model
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