[show abstract][hide abstract] ABSTRACT: A new version of the E-Cell simulation system,which runs on Windows as well as Linux, has been released as free software under the terms of the GNU General Public License.
[show abstract][hide abstract] ABSTRACT: Molecular biology's advent in the 20th century has exponentially increased our knowledge about the inner workings of life. We have dozens of completed genomes and an array of high-throughput methods to characterize gene encodings and gene product operation. The question now is how we will assemble the various pieces. In other words, given sufficient information about a living cell's molecular components, can we predict its behavior? We introduce the major classes of cellular processes relevant to modeling, discuss software engineering's role in cell simulation, and identify cell simulation requirements. Our E-Cell project aims to develop the theories, techniques, and software platforms necessary for whole-cell-scale modeling, simulation, and analysis. Since the project's launch in 1996, we have built a variety of cell models, and we are currently developing new models that vary with respect to species, target subsystem, and overall scale.
[show abstract][hide abstract] ABSTRACT: 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.
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.
The E-CELL software is available upon request.
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/.
[show abstract][hide abstract] ABSTRACT: To characterize the extent of DNA methylation and its possible biological roles in a wide variety of organisms, we have analyzed gene sequences extracted from the GenBank database. Sequences of both methylated and non-methylated species were used for comparative analysis. The local CpG dinucleotide distribution near the 5' ends of genes as well as the degree of overall CpG suppression/depletion in the entire gene region were examined in all complete gene sequences for each species. We show that the distribution patterns of CpG near the 5' region of genes differ among vertebrates, invertebrates, plants and bacteria. CpG island-like peaks in CpG O/E (observed/expected ratio) were observed not only in methylated species, but also in non-methylated species. In methylated non-vertebrates, overall CpG O/E values were lower, and peaks in the CpG profile of 5' regions were larger than in non-methylated species. We discuss the implications of such biases with respect to DNA methylation.