1. SRI International Bioinformatics 1 Navigation to Related Objects Bioinformatics Research Group SRI International latendre@ai.sri.com Mario Latendresse October 2010, Pathway Tools Workshop

2. SRI International Bioinformatics 2 Available on the Web Applies for compounds, genes, proteins, reactions, pathways Once such an object is found, a new menu appears on the right on the top menu bar The menu offers to search the object found: 1. In all databases or 2. Another database The In all databases is demanding (BioCyc has over 1000 databases); more so for genes and proteins

3. SRI International Bioinformatics 3 Does this Object Exist in Other PGDBs?

4. SRI International Bioinformatics 4 How is Similarity Computed? For pathways, reactions, and compounds: based on frame-ids (unique identifiers) For proteins and genes: based on names, synonyms, and orthologs l The result page tells you, for each database, if found based on name/synonyms or orthologs, or both

5. SRI International Bioinformatics 5 Demo on the Web of another database 1. At BioCyc.org, select E. coli K12 as the database to search 2. Search for the glycolysis pathway using the Search->Pathways command 3. Once the glycolysis pathway is displayed, Select the command Pathway->Show this pathway in another database 4. Select the database to search (e.g., MetaCyc) 5. If it exists in the other database, the glycolysis pathway is displayed for this database

6. SRI International Bioinformatics 6 Demo on the Web of in all databases 1. At BioCyc.org, select E. coli K12 as the database to search 2. Search for compound N-methyltryptophan. 3. Once the compound is displayed, select the command Compound->Show this compound in all databases 4. About 28 databases (the number depends on the current version of BioCyc.org) are found containing that compound

7. SRI International Bioinformatics 7 Result for In all databases for a Compound

8. SRI International Bioinformatics 8 For Genes and Proteins The search for similar proteins and genes is based on names (name and synonyms) and orthologs The result page gives the reasons of the match

9. SRI International Bioinformatics 9 Result In all databases for a Gene

10. SRI International Bioinformatics 10 Implementation The two commands are implemented using BioVelo. A general purpose query language for Pathway Tools The query itself can be saved since it appears as a URL in the browser

11. SRI International Bioinformatics 11 Implementation (2) Searching all databases for a pathway [ ( Z1,r ): Z1<-dbs, r := Z1~GLYCOLYSIS ] Searching all databases for a compound [ (Z1,r,r^Chemical-formula): Z1 <- dbs, r:=Z1~PEPTIDE-TRYPTOPHAN ] Searching all databases for a reaction [ (Z1,r,r^EC-number): Z1 <- dbs, r := Z1~L-IDITOL-2-DEHYDROGENASE-RXN ] Searching all databases for a gene [ r : l1 := find-objects(META,ECOLI~EG11024), l2 := find-orthologs(META,ECOLI~EG11024), both := l1**l2, ort := l2 -- both, sim := l1 -- both, r <- … both … ort … sim …]

12. SRI International Bioinformatics 12 Navigation to Related Objects Questions?