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As databases of biological
structure and function grow, there is an increasing demand for computational
methods that integrate information from diverse sources, reconstruct
biological networks, predict the physiological functions of cellular
networks, and integrate structurally across scales of biological
organization from molecule to organism.
On March 28-30, 2005 at the Catamaran Hotel in San Diego’s Mission Bay, we
hosted a two-day satellite meeting to the 2005 International Congress of
Physiological Sciences. The meeting, entitled, “Computational Physiology:
From Genome to Physiome,” was organized under the auspices of the National
Biomedical Computation Resource and the Physiome and Bioengineering
Committee of the IUPS. Major sponsorship was provided by the NIH through the
National Center for Research Resources, and additional funding was received
through generous educational grants from Dell, IBM (USA and NZ) and Pfizer
Global Research and Development.
The meeting was attended by over 80 scientists from 10 countries in the
Americas, Asia, the Pacific and Europe including a strong representation of
graduate studies and postdoctoral trainees. Twenty-three invited speakers
and over 20 posters spanned a range of topics from bioinformatics, systems
biology, metabolic engineering and computational cell biology to multi-scale
imaging and modeling of tissue, organ and system physiology in health and
diseases.
The satellite marks the latest in a series of international workshops on the
theme of the “Physiome Project,” a concept that was first presented in a
report from the Commission on Bioengineering in Physiology to the IUPS
Council at the 32nd International Congress in Glasgow in 1993. The term
“physiome” comes from “physio” (life) + “ome” (as a whole), and is intended
to provide a “quantitative description of physiological dynamics and
functional behavior of the intact organism”1. A satellite workshop “On
designing the Physiome Project,” organized by James Bassingthwaighte, Chair
of the then IUPS Commission on Bioengineering in Physiology, was held in
Petrodvoretz, Russia, following the 33rd International Congress in St
Petersburg in 1997. A synthesium on the Physiome Project was held at the
34th International Congress of the IUPS in Christchurch, New Zealand, in
August 2001, and the Physiome Project was designated by the IUPS executive
as a major focus for IUPS during this decade. The Physiome Commission of the
IUPS was created in 2000 and later combined with the Bioengineering
Commission into the IUPS Physiome and Bioengineering Committee, co-chair by
Peter Hunter and Aleksander Popel. Since the Physiome Project was launched
by IUPS, many of the annual meetings of bioengineering societies have
included physiome tracks in their programs.
The satellite meeting in Mission Bay continued to advance the physiome
concept and its goals by exploring the interface between in-silico systems
biology and multi-scale computational biology. During the first day of the
meeting, Shankar Subramaniam (UCSD) and Giovanni Paternostro (The Burnham
Institute) described new progress in the systems biology of complex
phenotypes including diabetes and aging using bioinformatic and genome-scale
phenotyping methods. Jeffrey Hasty (UCSD), Jeremy Rice (IBM Research) and
Trey Ideker (UCSD) described the reconstruction and modeling of networks of
protein-DNA and protein-protein interactions. Bernhard Palsson (UCSD)
introduced a comprehensive reconstruction of the human mitochondrial
metabolic network and the use of constraint-based models to analyze
metabolite fluxes in genome-scale models. This set the stage for
presentations by James Bassingthwaighte (University of Washington), Satoshi
Matsuoka (Osaka University), and Nicolas Smith (University of Auckland) on
kinetic models of mitochondrial energy metabolism and myocardial ischemia.
The day ended with a dinner cruise on Mission Bay.
Peter Hunter (University of Auckland) introduced the second day with an
update on the progress of the Physiome project with special emphasis on the
development of XML-based “markup languages” such as CellML as standardized
encodings of cell systems models and the growing databases of models3
available using these languages. Dan Cook (University of Washington) and
Brian Athey (University of Michigan) expanded on this theme discussing
ontologies and frameworks for integrative modeling and infrastructure and
strategies for team science.
Leslie Loew (University of Connecticut), Maryann Martone (USCD) and Tom
Bartol (The Salk Institute) spoke in a session on multi-scale models of
single cells in which they described community software and data resources
such a Virtual Cell4, the Cell-Centered Database5 and MCell6.
Denis Noble (Oxford University) led the session on cardiac cell modeling
with a survey of computational models of cardiac myocyte ion currents and
their application to unraveling arrhythmia mechanisms. He was followed by
Donald Bers (Loyola of Chicago) and Jeffrey Saucerman (UCSD) who focused on
modeling cardiac myocyte excitation-contraction coupling, intracellular Ca
handling and the signaling pathways that regulate them.
Multi-scale analyses at the tissue, organ and whole body scales, their
application to diagnosis and therapeutic mechanisms and the power of
visualization in these settings were discussed by Craig Henriquez (Duke
University), Alan Garfinkel (UCLA), Natalia Trayanova (Tulane), Yoram Rudy
(Washington University) and Christopher Johnson (University of Utah).
The satellite succeeded in demonstrating the new degree of integrative
physiological understanding that is becoming possible with the latest
advances in computational biology from genome to physiome. A special issue
of Experimental Physiology with selected papers from the meeting will be
published soon. The goal of predicting phenotype from the combination of
genotype and environmental influences is closer than ever before, and future
meetings should be encouraged. More information on the satellite, including
abstracts of presentations and posters, can be found at
http://nbcr.net/physiome/.
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| Attendees at the IUPS
Satellite on Computational Physiology enjoyed lunch outside by the beach
in San Diego’s Mission Bay. |
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| Shu Chien
taking first place in the keg race with Martin Frank during the IUPS
Beach Party. |
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| Animal rights
demonstrators protesting the presence of the IUPS Congress in San Diego. |
References:
Bassingthwaighte JB. Strategies for the Physiome Project. Annals of
Biomedical Engineering 28, 1043-1058, 2000.
Hunter P J, Borg, T. Integration from Proteins to Organs: The Physiome
Project, Nature, 4(3), 237-243, 2003.
Lloyd CM, Halstead MD, Nielsen PF. CellML: its future, present and past.
Prog Biophys Mol Biol.85(2-3):433-50, 2004
Slepchenko BM, Schaff JC, Macara I, Loew LM. Quantitative cell biology with
the Virtual Cell. Trends Cell Biol. 13(11):570-6, 2003
Martone ME, Zhang S, Gupta A, Qia X, He H, Price DL, Wong M, Santini S,
Ellisman MH. The cell-centered database: a database for multiscale
structural and protein localization data from light and electron microscopy.
Neuroinformatics 1(4):379-95, 2003
Coggan JS, Bartol TM, Esquenazi E, Stiles JR, Lamont S, Martone ME, Berg DK,
Ellisman MH, Sejnowski TJ. Evidence for ectopic neurotransmission at a
neuronal synapse. Science 15;309(5733):446-51, 2005.
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