SRI International Bioinformatics 1 Submitting pathway to MetaCyc Ron Caspi

2 SRI International Bioinformatics Why Curate a PGDB? A well curated PGDB can serve as a central online resource that integrates many types of information about an organism Novel pathways from organism-specific PGDBs can be imported into MetaCyc, where they improve the quality of all future PGDBs requires modest resources- a part time curator is all it takes. A pathway can be researched and curated in as little as a day or two, although complicated pathways take much longer. Raise funding for a curation project!

3 SRI International Bioinformatics What Exactly is Curation? Correction of false-positive and false-negative predictions Incorporation of information from experimental literature Authoring of comments and citations Ongoing updating and refinement of a PGDB Gene positions, names, synonyms Protein functions, activators, inhibitors, reactions catalyzed Addition of new pathways, modification of existing pathways Defining TF binding sites, promoters, control of transcription initiation Updating database fields

4 SRI International Bioinformatics Overview of Creating a Pathway Identify the reactions in the pathway, and look up the EC numbers (if applicable) Find the individual reactions in the PGDB/MetaCyc, and create new reactions if necessary. You may need to create new compounds as well Compose the pathway from the individual reactions using the pathway editor Add commentary and citations Assign the appropriate enzymes, create complexes when appropriate. Curate full information for enzymes and genes. QA: make sure that the pathway has an associated class, and that every enzyme (and the pathway) has an evidence code.

5 SRI International Bioinformatics Run the Consistency Checker The Consistency Checker finds data errors and inconsistencies that you would have never suspected to exist in your PGDB. It is very important to run it and fix the errors that it finds. Running the Consistency Checker is like changing the oil in your car!

6 SRI International Bioinformatics Create and Use Author and Organization Frames

7 SRI International Bioinformatics Add Pathway Evidence Codes Evidence Codes Definition: Experimental evidence codes: IDA: inferred from direct assay IEP: inferred from expression pattern IPI: inferred from physical interaction TAS: traceable author statement IGI: inferred from genetic interaction IMP: inferred from mutant phenotype

8 SRI International Bioinformatics Add Literature References If a PubMed ID exists enter it in the citation box. This saves you work, and will provide hyperlinks to the PubMed abstract pages. If there is no PubMed ID, use the format “Smith89” PubMed references need to be imported manually

9 SRI International Bioinformatics Add Pathway Summaries Add any comments that are appropriate for the pathway Do not add comments about a specific enzyme or reaction in here Use the CITS button for literature citations You can embed web hyperlinks in the text (use the Hyperlink button) You can refer to other objects in the database by generating internal hyperlinks to these objects (FRAME button)

10 SRI International Bioinformatics Use Internal Hyperlinks

11 SRI International Bioinformatics Specify Enzyme Complexes

12 SRI International Bioinformatics Use Enzymatic Activity and/or Enzyme Names Correctly In some cases the two names are different Example: for the enzymes “pyruvate kinase I” and “pyruvate kinase II”, the enzymatic activity name is “pyruvate kinase”

13 SRI International Bioinformatics Example for a Submitted Pathway

14 SRI International Bioinformatics Submit Your Pathways to MetaCyc Right-click on the pathway name, and choose Edit - Add pathway to File Export List Click on the File menu, and choose Export - Selected Pathways to Lisp-Format File the file to biocyc- or to any curator.biocyc-