I M S B
MMD- A Mathematical Modeling Database for Cell Signaling Pathways.
V. Mahesh*, M. Breit, G. Enzenberg, B. Pfeifer, R. Modre-Osprian, B. Tilg
Institute for Biomedical Signal Processing and Imaging, University for Health Sciences, Medical Informatics and Technology,
Hall in Tirol, Austria. [email protected]
imsb.umit.at
DBiBD 2005 National e-Science Centre,
Edinburgh, Scotland, UK
I M S BRoadmap
• Motivation
• Need of an Integrative Environment
• Knowledge Utilization
• Integrative Environment
• MMD Core Schema
• Results
• Current Status of MMD
• Discussion and Outlook
I M S BMotivation and GoalMotivation
• Improving the level of understanding cell signaling pathways will have a number of potential and practical applications for medications and drug design.
• For example TNFα mediated NF-κB signaling pathway takes part in:– Cancer, Diabetes, Morbus Crohn– Protein-Protein Interaction-Networks.
Goal
• Building up of a knowledgebase.• That stores biological information.• That stores modeling information (including mathematical models) concerning pathways.
I M S BNeed of an Integrative Environment
Hypothesizedmechanistic
diagram
Experimentaldesign
Mathematicalmodeling
Mathematical analysis
Predictions
Experimentalmethods
Time coursemeasured data
Match ?
No
SimulationTranslation
I M S BKnowledge Utilization
Conceptual Models
Biocarta: EGF MAPK Kaskade
Mathematical Model
Biological Databases
Schoeberl B et al. Nat Biotechnol. 2002 Apr;20(4):370-5.
I M S B
Biological Knowledge Modeling Knowledge
Modeling Tools
Simulation &Analysis
Pathway Tools
Biological Interpretation
Combing Abstract Knowledge
I M S B
KEGG
DIP
GO
IntegratedWorkspace
Mathematical Modeling Database
Designing Environment
Data exchange between PathBlazer and MMD
BIND
CZDB
Modeling data handling
Simulation Environment
Integrative Environment
MS-SQL Server2000
Data exchange between Matlab and MMD
BIND,DIPBiological
Dataset
SimulationDataset
Modeling Dataset
I M S B
Knowledgebase (KB): Information about pathways, interactions and their association to components that includes modeling dataset.
Pathways: A group of interacting components.
Reactions:
A group of components that undergo a transformation.
Components: It can be a protein, DNA/RNA, sub molecule, etc that is involved in a reaction.
Organizational Structure of MMD
Results
Pathways
Reactions
Components
Knowledgebase
I M S BDatabase Core Schema
Components
Reactions
Pathways
I M S B A Model stored in MMDBouwmeester T, etal. Nat Cell Biol. 2004 Feb;6(2):97-105
TNF pathway model.Cho KH, etal. Simulation. 2003 Dec;79(12):726-39
I M S BComponent & Reaction records of MMD
Component_ID
Name Component_Description
Disease
Formula
Source
Created
1472 TNFR1 Tumor necrosis factor receptor superfamily, member 1A; tumor necrosis factor-alpha receptor; tumor necrosis factor binding protein 1. A member of the TNF-receptor superfamily. One of the major receptors for the tumor necrosis factor-alpha. Germline mutations of the extracellular domains of this receptor were found to be associated with the autosomal dominant periodic fever syndrome. Note that the GI refers to an incomplete description of the molecule, [mat_peptide:22-455]. OMIM:191190
Biological
28.01.20
04 14:44:05
Reaction_ID Reaction_NameReaction_Description
DiseaseReaction_Formu
laCreated
Datasource
40105 TNFalpha/TNFR1 association and dissociation
-(k1)*(m1)*(m2) +(k2)*(m3) +(k24)*(m24) +(k13)*(m12)
05.07.2004 11:42:46
IMSB
I M S BCurrent Status of MMD
1. We have incorporated biological knowledge from the online protein databases
like BIND,DIP and others, into our database.
2. We implemented and tested the TNFpathway model based on Cho et al. within our environment.
3. We extended the TNFpathway model of Cho using the integrative environment.
4. We implemented data handling tools between different parts of the integrative environment, e.g., pathway-XML file handling tool in Matlab to extract modeling information (set of ODEs).
I M S BDiscussion & Outlook• Expanding the Database Schema
- Experimental and Clinical data.
- Protein complex building.
- Validation of implemented pathway models.
• Further Work
- Extending the database schema for including simulation results.
- Incorporate a flexible data exchange format using XML that
supports us to exchange the data e.g., using Biopax.
- Incorporating BIOUML or Cytoscape tool into our environment for
a more global visualization.
I M S BTeam
Integrativer Environment,Database
Computational Systems Biology
Biological and Clinical Questions
Modeling and Simulation of Signaling Pathways.
Mahesh Visvanathan, M.Sc. Breit Marc, M.Sc.
Enzenberg Gernot, Dr.Bernhard Pfeifer, Dip.-Ing. Modre-Osprian Robert, Dr.
Tilg Bernhard, Prof., Dr.