IMSB
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.
mahesh.visvanathan@umit.at
imsb.umit.at
DBiBD 2005
National e-Science Centre,
Edinburgh, Scotland, UK
Roadmap
• Motivation
• Need of an Integrative Environment
• Knowledge Utilization
• Integrative Environment
• MMD Core Schema
• Results
• Current Status of MMD
• Discussion and Outlook
IMSB
Motivation and Goal
IMSB
Motivation
•
•
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.
Need of an Integrative Environment
IMSB
Hypothesized
mechanistic
diagram
Translation
Mathematical
modeling
Mathematical
analysis
Simulation
No
Predictions
Match ?
Experimental
methods
Experimental
design
Time course
measured data
Knowledge Utilization
Biological Databases
IMSB
Conceptual Models
Biocarta: EGF
MAPK Kaskade
Mathematical Model
Schoeberl B et al. Nat Biotechnol.
2002 Apr;20(4):370-5.
Combing Abstract Knowledge
Biological Knowledge
IMSB
Modeling Knowledge
Modeling
Tools
Pathway
Tools
Biological
Interpretation
Simulation &
Analysis
Integrative Environment
Simulation Environment
Integrated
Workspace
KEGG
DIP
GO
Modeling data handling
BIND
Designing Environment
CZDB
Data exchange between Matlab
and MMD
Data exchange between
PathBlazer and MMD
Mathematical Modeling Database
MS-SQL Server2000
BIND,DIP
Biological
Dataset
IMSB
Modeling
Dataset
Simulation
Dataset
Organizational Structure of MMD
Knowledgebase (KB):
Information about pathways, interactions
and their association to components that
includes modeling dataset.
Pathways:
A group of interacting components.
Results
Knowledgebase
Pathways
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.
IMSB
Reactions
Components
Database Core Schema
Components
Reactions
Pathways
IMSB
A Model stored in MMD
IMSB
Bouwmeester T, etal. Nat Cell Biol.
2004 Feb;6(2):97-105
Cho KH, etal.
Simulation. 2003
Dec;79(12):726-39
TNF a pathway model.
Component & Reaction records of MMD
IMSB
Com
pone
nt_I
D
147
2
Name
TNFR1
D
i
s
e
a
s
e
Component_Description
F
o
r
m
u
l
a
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
Reaction_ID
Reaction_Name
40105
TNFalpha/TNFR1
association and
dissociation
Reaction_Des
cription
Disease
Reaction_Formu
la
-(k1)*(m1)*(m2)
+(k2)*(m3)
+(k24)*(m24)
+(k13)*(m12)
S
o
u
r
c
e
B
io
lo
gi
c
al
Created
05.07.2004
11:42:46
Cre
ated
28.0
1.20
04
14:4
4:05
Dataso
urce
IMSB
Current Status of MMD
IMSB
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 TNFa pathway model based on Cho et al.
within our environment.
3.
We extended the TNFa pathway 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).
Discussion & Outlook
IMSB
• 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.
Team
IMSB
Computational
Systems Biology
Integrativer Environment,
Database
Mahesh Visvanathan, M.Sc.
Breit Marc, M.Sc.
Enzenberg Gernot, Dr.
Bernhard Pfeifer, Dip.-Ing.
Modre-Osprian Robert, Dr.
Tilg Bernhard, Prof., Dr.
Modeling and Simulation of
Signaling Pathways.
Biological and
Clinical Questions