Recent Developments and Future Directions in Pathway Tools Peter D. Karp SRI International

SRI International Bioinformatics Recent Developments Two Pathway Tools releases per year: May and November Release notes are at notes.html notes.html Note which software component, and whether change applies to desktop, Web, or both Upgrades recommended at least once per year

SRI International Bioinformatics Recent Developments – Version 9.5 New Interfaces to Oracle and MySQL New ontology of cellular components Navigator l More interactivity in Overview l Display of Omics data on individual pathways l Save Omics viewer displays l Comparative genomics u Align orthologous genes u Summary tables u Cross-species comparison of reactions and pathways

SRI International Bioinformatics Recent Developments – 9.5 Navigator l Genome browser improvements – Pseudogenes, center gene by clicking on tick mark, TU grey background l Show frame in all databases l Promoters and TF binding sites with low quality evidence are drawn using dashed lines Editors l Marvin chemical editor available l Embed hyperlinks to PGDB objects within comments l Reaction merging

SRI International Bioinformatics Recent Developments– 9.5 PathoLogic l Inference of transport reactions u Inferred from free-text descriptions of protein functions in Common- Name slot u GUI permits review and editing of inferred reactions u Example: L-lysine [periplasm] + ATP = L-lysine + ADP + Pi l Pseudogenes handled correctly l Other PGDBs can be used as reference DBs for pathway prediction l Windows port

SRI International Bioinformatics Recent Developments – Version 9.0 Navigator l New genome browser l More compact pathway diagrams l Improved operon depiction in gene pages

SRI International Bioinformatics Recent Developments – Version 8.5 Cellular Overview and Omics Viewer Improved l Users can create combined displays of gene expression, proteomics, metabolomics, and reaction flux measurements on the Omics Viewer l Drawing speed is improved l Metabolic pathways in the Overview are now grouped by pathway class l Zooming of the diagram is supported (desktop version only) l The periplasm and outer membrane have been added to the diagram, as have those proteins present in the periplasm and outer membrane l The layout of the Cellular Overview can be computed completely automatically by PathoLogic in a new PGDB Compound stereochemistry supported Support for JME chemical editor, molfile import/export

SRI International Bioinformatics Bug Reports Comprehensive bug reports are critical to allowing fast solutions l Platform and Pathway Tools version l Error message l What operation was in progress when error occurred l Backtrace :zoom :count :all

SRI International Bioinformatics Coming in Version 10.0 and Later Support for GO l Representation of GO, but no inference Semantic zooming in Overview Working on display of names in Overview Improvements to pathway graphics Expand comparative genomics New advanced query web interface Detect dead-end metabolites

SRI International Bioinformatics What Other Features are Needed? Contributions from other groups can accelerate development of Pathway Tools Past contributions l SBML Export (J. Zucker) l Import/Export tool (L. Goldovsky)

SRI International Bioinformatics How to Stimulate Software Contributions Distribution models l SRI distributes l Developer distributes SRI runs 3 rd -party inference tools during BioCyc generation How to accelerate development? l Tutorials on Pathway Tools internals? l Hackathons? l Tutorials on Lisp?

SRI International Bioinformatics Tools Needed Inference of GO terms Inference of cellular location Connect to Flux Balance Analysis software Genome properties Compare consistency of metabolic network to growth media requirements