The huge quantity of data and knowledge de?ned by the genome sequence of an organism, and by large numbers of other experimental ?ndings for the organism, requires a database (DB) as a central repository for information about the genome, the biochemical network, and the regulatory processes of that organism. The Pathway Tools software is a robust and comprehensive system for constructing organism-speci?c DBs and for pathway analysis of genomes. Pathway Tools enables communities of scientists to create, query, visualize, and analyze organism DBs, and to publish such DBs on the web. The software supports construction of organism DBs that combine a large number of bioinformatics datatypes, including genome maps, genes, operons, RNAs, proteins, chemical compounds, biochemical reactions, metabolic pathways, and regulatory interactions. Pathway Tools is a mature and production-grade software environment that has been used by 762 groups outside SRI to analyze 6,100 genomes. Pathway Tools further supports the creation of quantitative metabolic ?ux models from organism DBs. Such metabolic ?ux models have diverse applications. They enable computational predictions of which genes and reactions within the metabolic network are essential, thus facilitating the design of drugs against disease-causing bacteria. They support the engineering of new metabolic pathways, such as for bioenergy research. Metabolic models for individual organisms can be combined by using Pathway Tools in a plug-and-play fashion to create models of organism communities, such as for the human gut microbiome. Such models will be a primary means by which we create a predictive understanding of the human microbiome. We propose to extend the metabolic-modeling module of Pathway Tools to enable more accurate and rapid creation of metabolic models for individual organisms and for organism communities, and to model a wider range of organism interactions. We propose to create an interactive cellular dashboard and control panel that facilitates multi-level interpretation of metabolic-model results and of high-throughput datasets. And we propose to enhance the Pathway Tools metabolic network diagram to depict metabolic interactions within a community of organisms. We propose to provide support services for the large and growing user community for Pathway Tools, to maintain quality documentation for the software, and to create two thoroughly tested releases of the software per year.
The proposed project will generate software tools that increase the ability of scientists to use genome sequence data to advance human health. This software enables creating central database repositories and websites containing genome data and data on cellular networks for disease-causing bacteria and for experimental model organ- isms, such as the laboratory mouse. The software enables researchers to develop metabolic models describing the interactions of bacteria within the human microbiome to develop a predictive understanding of the microbiome to advance health.
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