Development and Support of the Pathway Tools Software - 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 and develop several new capabilities to enhance Pathway Tools, including the con- struction of a next-generation metabolic pathway prediction algorithm with improved accuracy based on ad- vanced machine-learning methods. We will also develop tools to support analysis of isotopic labeling experi- ments for metabolomics, to enable researchers to quickly track labeled atoms through biochemical networks. We will integrate multiple software tools for inferring virulence gene annotations, and for searching and comparing virulence genes and pathways. We will also develop tools for reporting the update operations made by a team of curators to aid in managing curation efforts and identifying which automated inference tools are most frequently corrected by curators. Pathway Tools is a mature and production-grade software environment which has been licensed 15,567 re- search groups from around the world, and which has been cited 2,603 times. We propose to maintain the software, such as by installing new versions of its many components, and by supporting the user community through train- ing, documentation, and bug fixing.
