Tomita Masaru [a]. Hashimoto Kenta [a]. Takahashi Kouichi [a]. Shimizu
Thomas Simon [a]. Matsuzaki Yuri [a]. Miyoshi Fumihiko [a]. Saito Kanako
[a]. Tanida Sakura [a]. Yugi Katsuyuki [a]. Venter J Craig. Hutchison
Clyde A, III.
E-CELL: Software environment for whole-cell simulation, Bioinformatics 15(1) :72-84, 1999.
Abstract
Motivation: Genome sequencing projects and further systematic functional
analyses of complete gene sets are producing an unprecedented mass of
molecular information for a wide range of model organisms. This provides us
with a detailed account of the cell with which we may begin to build models
for simulating intracellular molecular processes to predict the dynamic
behavior of living cells. Previous work in biochemical and genetic
simulation has isolated well-characterized pathways for
detailed analysis, but methods for building integrative models of the cell
that incorporate gene regulation, metabolism and signaling have not been
established. We, therefore, were motivated to develop a software environment
for building such integrative models based on gene sets, and running
simulations to conduct experiments in
silico. Results: E-CELL, a modeling and
simulation environment for biochemical and genetic
processes, has been developed. The E-CELL system allows a user to define
functions of proteins, protein-protein interactions, protein-DNA
interactions, regulation of gene expression and other features of cellular
metabolism, as a set of reaction rules. E-CELL simulates cell behavior by
numerically integrating the differential equations described implicitly in
these reaction rules. The user can observe, through a computer display,
dynamic changes in concentrations of proteins, protein complexes and other
chemical compounds in the cell. Using this software, we constructed a model
of a hypothetical cell with only 127 genes sufficient for transcription,
translation, energy production and phospholipid synthesis. Most of the genes
are taken from Mycoplasma genitalium, the organism having the smallest known
chromosome, whose complete 580 kb genome sequence was determined at TIGR in
1995. We discuss future applications of the E-CELL system with special
respect to genome engineering. Availability: The E-CELL software is available
upon request. Supplementary information: The complete list of rules of the
developed cell model with kinetic parameters can be obtained via our web site
at: http://e-cell.org/. Contact: mt@sfc.keio.ac.jp
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