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Digital Human Meeting
FAS, July 23, 2001
NLM, Bethesda, MD
“Biology must graduate
from the cartoon diagram.”
-Bruce Alberts, NAS President
Princeton Institute for Integrative Genomics
Symposium on Biological Networks
May 2001
2001 Physiome Sciences, Inc. All rights reserved.
The Physiome Sciences Vision…
Providing technology to enable the creation
of computer-based biological models from
subcellular to organism levels
Promoting the acceptance of standards to
permit the integration, exchange, and
extension of models across organizational and
geographic boundaries
2001 Physiome Sciences, Inc. All rights reserved.
Physiome Sciences’ Approach
Hierarchical modeling of biology
Individual
Pathways
Signaling
systems
Cell
Organs
Organ
Systems
2001 Physiome Sciences, Inc. All rights reserved.
Pitfalls in building biological
models
“Point” solutions
Models should be reusable and extensible
“Black boxes”
Data and assumptions should be accessible
Static data content
Models should be able to integrate new data as
they become available
2001 Physiome Sciences, Inc. All rights reserved.
Overcoming pitfalls: In Silico
CellTM architecture
3rd party applications
Modeling
tools
Database
CellMLTM
Mathematics
MathML
Simulations
2001 Physiome Sciences, Inc. All rights reserved.
What is CellMLTM?
An extensible mark-up language (XML) that
Describes structure and mathematics of
(sub)cellular models
Embeds metadata and documentation
Defines an extension mechanism
Facilitates re-use of models and model components
(encapsulation)
Biological scope examples version 1.0:
Excitable cells
Reaction networks
Signaling pathways
2001 Physiome Sciences, Inc. All rights reserved.
Why CellMLTM?
Models are traditionally hard-coded in C, C++,
Matlab, Mathematica
Publications often contain an incomplete set of
equations and data
Very difficult to duplicate results and to
exchange and extend models
CellML permits users to exchange all the
information needed to represent (and run) a
model
2001 Physiome Sciences, Inc. All rights reserved.
Development of CellMLTM
as an open standard
“Physiome” Mark-Up Languages (CellML,
FieldML, AnatML) developed as open
standards in collaboration with University of
Auckland
Website: www.CellML.org
Mailing List: [email protected]
Edit/Run/Validate Tools for CellML (Q3 2001)
CellML model repository (Q4 2001)
2001 Physiome Sciences, Inc. All rights reserved.
Source: Jim Broach, Princeton University
Modeling tool: Pathway Editor
2001 Physiome Sciences, Inc. All rights reserved.
Modeling tool: Cell Editor
• Permits integration of
biochemistry (pathways)
and electrophysiology
within a cell-based tool
• Outputs models to other
software platforms for
assembling more
complex (organ, system)
models
2001 Physiome Sciences, Inc. All rights reserved.
Modeling cardiac heterogeneity:
single cell response to drug
Experimental data
from Burashnikov and
Antzelevitch, 1998
Simulated Data
BCL = 300, 500, 1000, 2000, 4000,
6000 msec
2001 Physiome Sciences, Inc. All rights reserved.
Modeling cardiac heterogeneity:
integrate from single cell to tissue
Anatomy
Ion channel density
Physiology
AP
IKs
Ito
Epi
INa (late)
ECG
Endo
1x
6x
Expression level
Anatomy
Genome
Physiome
2001 Physiome Sciences, Inc. All rights reserved.
Predicting cardiac safety
Antihistamines
Simulated cellular APs
at 3 concentrations
Input data
Simulated ECG
analysis
Amount of drug block
DQT
Worse
DAPD

DQT
Better
DAPD

Concentration (µM)
IKs
IKr
Ito
2001 Physiome Sciences, Inc. All rights reserved.
Summary
Physiome is working to provide a flexible framework for
modeling biology across scales from the subcellular
upwards.
Spatial heterogeneity in cardiac muscle as a case study
towards integrated modeling of the heart.
XML-based standards (CellML, SBML, FieldML, AnatML)
will facilitate exchange and reuse of models and
components. We’ll have tools out soon.
Open source? We’re interested, but have yet to adopt an
official stance.
2001 Physiome Sciences, Inc. All rights reserved.
for more info:
www.physiome.com
[email protected]
2001 Physiome Sciences, Inc. All rights reserved.