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

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Recent Developments andFuture
DirectionsinPathway ToolsPeter D. KarpSRI
International
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Recent Developments

• Two Pathway Tools releases per year May and
  November
• Release notes are at http//bioinformatics.ai.sri
  .com/ptools/release-notes.html
• Note which software component, and whether change
  applies to desktop, Web, or both
• Upgrades recommended at least once per year

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Recent Developments Version 9.5

• New Interfaces to Oracle and MySQL
• New ontology of cellular components
• Navigator
• More interactivity in Overview
• Display of Omics data on individual pathways
• Save Omics viewer displays
• Comparative genomics
• Align orthologous genes
• Summary tables
• Cross-species comparison of reactions and
  pathways

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Recent Developments 9.5

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

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Recent Developments 9.5

• PathoLogic
• Inference of transport reactions
• Inferred from free-text descriptions of protein
  functions in Common-Name slot
• GUI permits review and editing of inferred
  reactions
• Example L-lysine periplasm ATP L-lysine
  ADP Pi
• Pseudogenes handled correctly
• Other PGDBs can be used as reference DBs for
  pathway prediction
• Windows port

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Recent Developments Version 9.0

• Navigator
• New genome browser
• More compact pathway diagrams
• Improved operon depiction in gene pages

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Recent Developments Version 8.5

• Cellular Overview and Omics Viewer Improved
• Users can create combined displays of gene
  expression, proteomics, metabolomics, and
  reaction flux measurements on the Omics Viewer
• Drawing speed is improved
• Metabolic pathways in the Overview are now
  grouped by pathway class
• Zooming of the diagram is supported (desktop
  version only)
• The periplasm and outer membrane have been added
  to the diagram, as have those proteins present in
  the periplasm and outer membrane
• 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

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Bug Reports

• Comprehensive bug reports are critical to
  allowing fast solutions
• Platform and Pathway Tools version
• Error message
• What operation was in progress when error
  occurred
• Backtrace zoom count all

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Coming in Version 10.0 and Later

• Support for GO
• 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

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What Other Features are Needed?

• Contributions from other groups can accelerate
  development of Pathway Tools
• Past contributions
• SBML Export (J. Zucker)
• Import/Export tool (L. Goldovsky)

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How to Stimulate Software Contributions

• Distribution models
• SRI distributes
• Developer distributes
• SRI runs 3rd-party inference tools during BioCyc
  generation
• How to accelerate development?
• Tutorials on Pathway Tools internals?
• Hackathons?
• Tutorials on Lisp?

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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