SRI International Bioinformatics 1 Pathway Tools Features Available Only in the Desktop Version PathoLogic

2 SRI International Bioinformatics PathoLogic PathoLogic is a module of the Pathway Tools software that builds Pathway/Genome databases Invoked from the Tools menu in the desktop version only

3 SRI International Bioinformatics PathoLogic: Inference of Metabolic Pathways Annotated Genomic Sequence Pathologic Integrates genome and pathway data to identify putative metabolic pathways Gene Products DNA Sequences Genes/ORFs Reactions Pathways Compounds Transporters Genes Operons Pathway Holes Pathways Compounds Gene Products Reactions MetaCyc Pathway/Genome Database Protein complexes Fast automated generation of organism-specific PGDBs

4 SRI International Bioinformatics Input Project Information Specify a name for the PGDB Specify the organism If there is an NCBI taxonomy ID for this organism, use it. You can specify authors, citations, contact , copyrights, a project home page etc

5 SRI International Bioinformatics Specifying the Genetic Elements A replicon editor opens up, facilitating specification of the different genetic elements present in the organism. Specify the files with annotation and sequence data for each genetic element.

6 SRI International Bioinformatics Trial Parse Once the input has been specified, the software can perform a trial parse, to provide quick confirmation that everything is ready for PGDB generation

7 SRI International Bioinformatics The Build Process is Largely Automatic What PathoLogic does during the automatic build: Parses the input files Creates objects for every gene and gene product Uses EC numbers, GO annotations and name matching to match enzymes to reactions in MetaCyc Imports catalyzed reactions and compounds from MetaCyc Generates a list of enzymes that couldn’t be assigned to reactions Infers pathways Generates Overview Diagrams Generates reports

8 SRI International Bioinformatics Post-Build Tasks Refine -> Assign Probable Enzymes Refine -> Assign Modified Proteins Refine -> Create Protein Complexes Refine -> Rescore Pathways Refine -> Predict Transcription Units Refine -> Transport Inference Parser (TIP) Refine -> Update Overview Refine -> Pathway Hole Filler

9 SRI International Bioinformatics Assign Probable Enzymes

10 SRI International Bioinformatics Transport Inference Parser (TIP) TIP constructs transport reactions by intelligent parsing of text in annotations. For example, the following annotation (in a Gram-negative bacterium): “Cation efflux family protein” lead to the creation of the reaction a cation [cytosol] = a cation [periplasmic space] TIP is an interactive tool – curators can go over all reactions manually, if desired.

11 SRI International Bioinformatics Transport Inference Parser (TIP)

12 SRI International Bioinformatics Filling Pathway Holes Pathway Hole Curated DBs UniProt & PIR BLAST/GC Identify Candidates Evaluate Candidates w/ Bayes classifier New Genome Retrieve sequences from other organisms Fill Hole

13 SRI International Bioinformatics Filling Holes

14 SRI International Bioinformatics PathoLogic Limitations PGDBs generated by PathoLogic provide access to all of Pathway Tools features, including simple, intuitive queries and powerful analysis tools. However, keep in mind that PGDBs generated by PathoLogic are computationally-predicted, and are likely to contain many errors In order to improve the quality of the database, consider manual curation

15 SRI International Bioinformatics The PGDB Registry

16 SRI International Bioinformatics The PGDB Registry The PGDB Registry is a utility that lets Pathway Tools users share PGDBs with each other The Registry is based after the Napster™ model PGDBs remain on their owner’s server, but are registered at SRI All users can query the SRI server from their copy of Pathway Tools, and download any Registry PGDB directly from the owner’s server

17 SRI International Bioinformatics The PGDB Registry

18 SRI International Bioinformatics The Registry – Schema Upgrades

19 SRI International Bioinformatics The Registry – Uploading Your PGDB The process of uploading a PGDB to the Registry is largely automated. See “Publishing PGDBs in the Registry” in the User Guide for details

20 SRI International Bioinformatics PGDB Collectors Downloaded PGDBs are listed with the download date, making it easy to see which ones may need to be updated. If you open many PGDBs, make sure you have a lot of RAM.