Bioinformatics, Vol 15, 72-84, Copyright © 1999 by Oxford University Press
M Tomita, K Hashimoto, K Takahashi, TS Shimizu, Y Matsuzaki, F Miyoshi, K Saito, S Tanida, K Yugi, JC Venter and CA Hutchison 3rd
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/.
ARTICLES
E-CELL: software environment for whole-cell simulation
Laboratory for Bioinformatics, Keio University, 5322 Endo, Fujisawa, 252, Japan.mt@sfc.keio.ac.jp
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