SRI International Bioinformatics 1 Advanced Editing of Pathway/Genome Databases Ron Caspi

SRI International Bioinformatics 2 General Curation

SRI International Bioinformatics 3 User Preferences

SRI International Bioinformatics 4 Create and Use Author and Organization Frames

SRI International Bioinformatics 5 Using the Text Editor ●Formatting ● italic, bold ● know your α, β ● Text wrapper: need two newlines to force a new paragraph ● Text wrapper: Never leave empty spaces at the end of a line ● An internal link to a reaction frame will print the reaction equation ● To print an enzymatic activity name use an internal link to the enzymatic activity frame ID, not the enzyme frame ID (important when an enzyme is multifunctional e.g. CPLX-6934 ). ● When providing multiple citations, use |CITS:[PMID1][PMID2| (rather than |CITS:[PMID1]|, |CITS:[PMID2]|. ●Special characters: ● Ångstrom Å (Å) ● Degree ° (◦)

SRI International Bioinformatics 6 Use Internal Hyperlinks

SRI International Bioinformatics 7 Use Variant Classes example: Putrescin Biosynthesis

SRI International Bioinformatics 8 Hypothetical Reactions, Excluded Enzymes Enzymes Not Used : useful when an enzyme is associated with a reaction, but does not participate in a specific pathway. For example, a catabolic enzyme in a biosynthetic pathway (e.g. EC , ornithine carbamoyltransferase) Hypothetical reactions: useful when a pathway step is proposed, but has not been proven Specified in the Pathway Info Editor

SRI International Bioinformatics 9 Super Pathways ●Need to keep pathways within well-defined end points ●Link pathways to upstream or downstream pathways with pathway links. ●Keep pathways simple ●Create more complex metabolic networks using superpathways ●Example: superpathway of aromatic compound degradation (aerobic)superpathway of aromatic compound degradation (aerobic) is composed of: ●catechol degradation II ●mandelate degradation I ●benzoate degradation (aerobic) ●  -ketoadipate degradation ●protocatechuate degradation II ●shikimate degradation ●quinate degradation ●4-hydroxymandelate degradation ●tryptophan degradation I

SRI International Bioinformatics 10 Advanced Curation

SRI International Bioinformatics 11 Using the Frame Editor The frame editor is powerful, but dangerous… Use it when there are no alternatives. Examples: ●Renaming frames ●Modified proteins ●Modifying dates of author credits ●Replacing an enzyme or reaction in an enzymatic-reaction frame ●Removing mistakes from pathway frames, such as predecessor pairs that the software ignores. ●Removing duplicated values from slots that should only have a single value (OFFIClAL-EC?) ●Investigated orphan enzymatic reaction frames reported by the consistency Checker

SRI International Bioinformatics 12 Protein complexes Adenosylmethionine decarboxylase is first synthesized as a proenzyme, and then self- cleaves into two smaller polypeptides. Each cleavage product forms a homotetramer, and the two complexes form a heterooctamer. A combination of editors enables creation of such multi-level complexes. Tutorial: Creating Protein Complexes

SRI International Bioinformatics 13 Classes and Instances ●Instance frames describe specific objects (e.g. a specific gene) ●Class frames describe general types of biological objects (e.g. the class of all genes) ●Proteins that are substrates of MetaCyc reactions are classes ●Every compound with an “R” in its structure should be a class

SRI International Bioinformatics 14 Converting an existing compound instance to a class ●Open the compound editor ●Click “Convert to Class” and exit ●Rename the frame to follow class name convention (if necessary) ●Modify the common name to start with “a” Modifications of MetaCyc classes is considered a schema change, and will be overwritten during the next update! Only use this procedure to correct curation errors that were introduced in your PGDB!

SRI International Bioinformatics 15 The Ontology Editor

SRI International Bioinformatics 16 The Ontology Editor ●Changing parent classes ●Adding parent classes ●Creating new classes to improve ontology Tutorial: the Ontology Editor

SRI International Bioinformatics 17 The Consistency Checker Consistency Checking should be performed routinely (every few months), and detected problems should be addressed

SRI International Bioinformatics 18 Consistency Checker – Automatic Tasks Bad Links MetaCyc pathways are extensively linked to other pathways. When new PGDBs are created by Pathologic, these links are still there, even if they point to pathways that are not present in the new PGDB. These links are only removed by the Consistency Checker.

SRI International Bioinformatics 19 Consistency Checker – Manual Tasks Example: create an empty |FRAME: | construct, then run the task “Check Frame References”

SRI International Bioinformatics 20 Exporting Pathways Between PGDBs ●To export a pathway to a file: (optional inclusion of enzymes and genes) ●Edit => Add Pathway to File Export List ●File => Export => Selected Pathways to Lisp-format File ●To import a pathway from file: ●File => Import => Pathways from File ●To export a pathway directly to another PGDB (both PGDBs must be installed on the same system): ●Edit -> Export Pathway to DB

SRI International Bioinformatics 21 Moving Objects Between PGDBs The following commands will import a frame from MetaCyc to EcoCyc: Both databases must be open before this will work. ●(import-compounds '(CPD-ID) (kb-of-organism 'meta) (kb-of-organism 'ecoli)) ●(import-reactions '(ID-RXN) (kb-of-organism 'meta) (kb-of-organism 'ecoli)) ●(import-proteins '(ID-MONOMER) (kb-of-organism 'meta) (kb-of-organism 'ecoli))

SRI International Bioinformatics 22 Exporting Graphics ●You can save any screen as a vector-based postscript file by using File -> Print ●The PS files are easily converted to PDF by Adobe Distiller (pat of the Acrobat Pro package) ●Graphics programs like Corel Draw or Illustrator can open the PDF files and let you manipulate the graphics ●The software also generates two posters – the cellular overview, and the genome poster. Those are also generated in postscript format.

SRI International Bioinformatics 23 Creating Links to External Databases ●To define a new external database link: ●File → Create → External Database Description ●Enter frame name ●Fill fields as shown in next slide ●To edit an existing link: ●Right-click on a link (from a Navigator page), and select “Edit External Database Info” ●Creating links to a PGDB see

SRI International Bioinformatics 24 External Database Editor

SRI International Bioinformatics 25 Polymerization example: folate polyglutamylation Ifolate polyglutamylation I

SRI International Bioinformatics 26 The Pathway Registry

SRI International Bioinformatics 27 The Registry – Schema Upgrades

SRI International Bioinformatics 28 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