Thursday, November 21, 2024
11/21/2024
Project Summary The huge breadth and depth of data and knowledge defined by the genome sequence of an organism, and by large numbers of other experimental findings 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 such organism-specific DBs. Path- way 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 bioin- formatics datatypes, including genome maps, genes, operons, RNAs, proteins, chemical compounds, biochemical reactions, metabolic pathways, and regulatory interactions. Pathway Tools further enables inference of qualitative metabolic reconstructions from sequenced genomes, and the creation of quantitative metabolic flux models from those reconstructions. Such metabolic models enable computational predictions of which genes and reactions within the metabolic network are essential, thus facilitating the design of drugs against disease-causing bacteria. We propose to research several new inference algorithms that derive new information for a sequenced pathogen genome for inclusion in Pathway Tools DBs. One algorithm will detect cross-feeding and cofactor- exchange relationships within a community of organisms to advance mechanistic understanding of the human microbiome. A second algorithm will enable rapid communication of the biochemical machinery of an organism encoded in its genome to scientists, such as during a disease outbreak. A third algorithm will improve the pre- diction of operons within bacterial genomes based on new features including RNA-seq data. We also propose to implement a suite of cloud-based editing tools for Pathway Tools databases that execute within the user's web browser. These editing tools will enable communities of scientists to work together to update and share knowl- edge about a given genome. Pathway Tools is a mature and production-grade software environment that 10,800 research groups around the world have licensed, and it has been cited 1,650 times. We propose to maintain the software, such as by installing new versions of its many components, and to support its user community through training, documentation, and bug fixing.
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