ti met may10

The Systems Biology Software Infrastructure

TiMet Workshop

May 7th 2010, Edinburgh

Richard Adams

www.sbsi.ed.ac.uk

http://sourceforge.net/projects/sbsi/

‘A new infrastructure to streamline the

connection between data, models, and

analysis,

allowing the updating of large scale

data, models

and analytic tools with greatly reduced

overhead’

SBSI - Overall objective

SBSI Contributors

Core developers

EPCC

Test Models and Evaluation

Project management

Circadian clock modellers

Stephen Gilmore PI

Nikos Tsorman Neil Hanlon

Galina Lebedeva

Alexey Goltsov

Azusa Yamaguchi

Kevin Stratford

People previously involved with SBSI

Shakir AliAnatoly Sorokin

Treenut SaithongStuart Moodie

Ozgur Akman

Igor GoryaninCarl Troein

Biopepa integration

Adam Duguid

Richard Adams

Requirements & Numerics

Andrew Millar

Graphical Notation

Network Inference

Process Algebras

Model analysis

Existing knowledge

High-resolution data

High-throughput data

New knowledge

Static models

Kinetic models

Systems Biology Software Infrastructure™

Kinetic Parameter Facility

Circadian clock

RNA metabolismInterferon signalling

Systems Biology Research, CSBE view

ERB-b signalling

Initial use case :Parameter Estimation Problem

• Building predictive models – challenging problem in Systems Biology

• Parameter estimation – critical stage in model development

• Multiple data sets needed for model calibration

• Optimization of large scale models –computationally challenging

• Circadian clock modelling project requires model optimization.

SBSI Numerics optimization

SBML model, Parameter constraints,Experimental Data

filesConfiguration file

Model.cpp,Datafiles,Parameter constraints

SBML->C++ conversion

-Best parameters-Cost function behaviour-Time course with best parameters

Eddie (ECDF)

Output

Using command line client

Run on HPC

retrieve results

Input

Integration of other CSBEprojects

BioPepa ✔

Outline of SBSI design

External model & experimentaldata sources

BioModels ✔

SBSI Dispatcher

(Task Manager)Compile C codes

Submit jobs to HPC ✔Retrieve results

✔Provide job status

SBSI Numerics

core

SBSI Visual

✔Desktop application✔Upload and edit SBML models Run simulations Configure and run optimisations✔Interact with external repositories✔Visualisation of data and results

Eddie (ECDF)

SBSI Numerics SBSI Numerics

SBSI serversSBSI Numerics

SBSI - complete system

Integration of other CSBE projects

BioPepa ✔ EPE

External model & experimentaldata sources

SBSI Visual

✔Desktop application✔Upload and edit SBML models Run simulations Configure and run optimisations✔Interact with external repositories✔Visualisation of data and results

SBSI Numerics

SBSI - local mode

SBSI Dispatcher

(Task Manager)Compile C codes

Submit jobs to HPC ✔Retrieve results

✔Provide job status

SBSI Numerics

CellDesigner

Eddie (ECDF)

SBSI Numerics SBSI Numerics

SBSI serversSBSI Numerics

A plugin for CellDesigner

CellDesigner –SBSI plugin

Nactem

CellDesigner

Dunnart

InSilicoIDESBSI

PathText Kleio

Panther Pathwaysdatabase

autolayouts

visualizes

annotates

Provides SBML models

Optimizes?

Sabio-RKdatabaseKinetic

parameters

Copasi

Ananiadou/Tsujii/Kemper

Mi (SRI) Funahashi/Ghosh

Nomura (Osaka)

updates

EHMN

Goryanin (Edinburgh)

Boyd (Melbourne)

4-6 July Manchester, 8-9 October Edinburgh (ICSB), OIST early March 2011

Existing organisations/interactions

Planned collaborations

Gilmore (Edinburgh)

GARUDA partners

Proposed collaborations

Multiple Cost Function

Optimizing Circadian Clock models with experimental data

BIOMD055: “Extension of a genetic network model by iterative experimentation and mathematical analysis.” by J. C. W. Locke, M. M. Southern, L. Kozma-Bognar, V. Hibberd, P. E. Brown, M. S. Turner, A. J. Millar (2005b). Molecular Systems Biology. 1:13The model has 57 parameters and 13 states( equations). Fitting data is 2 of those states obtained by experiment.

Using BG/L 128 nodes, it finished at 63140th generation by non-improvement criteria.The run time is 46 hours. Multiple Cost Function is used up to 6740 generation, after 6740th, only X2Cost is applied

Release code base on Sourceforge

Establish SBSI Numerics on Hector

Provide access to SBSI through CellDesigner

Develop user base /community

Publish!

SBSI goals 2010

In the workspace you can store models, data, objective functions and results

Editor view allows access to files

Data visualization panel

Step 1 – create a new SBSI project

Running parameter optimisations…

Running parameter optimisations…

Step 2 – choose models,data and algorithm type-multiple datasets can be selected

Step 3: choose parameters, constraints and initial values

Running parameter optimisations…

Running parameter optimisations…

Step 4: configure optimization algorithm

Step 5: Compare simulation using best parameters, with experimental data.