Editing Pathway/Genome Databases

SRI International Bioinformatics Pathway Tools Paradigm Separate database from user interface Navigator provides one view of the DB Editors provide an alternative view of the DB Reuse information whenever possible! l Compounds are the building blocks of reactions l Reactions are the building blocks of compounds l A PGDB should not describe the same biological entity more than once

SRI International Bioinformatics List of Editors Gene Editor Transcription Unit Editor Protein Editor Reaction Editor Chemical Compound Editor Pathway Editor Publication Editor Metabolic Overview Editor

SRI International Bioinformatics Invoking the Editors Right-Click on an Object Handle l Edit l Show

SRI International Bioinformatics Saving Changes The user must save changes explicitly with Save KB To discard changes made since last save l Special -> KB -> Revert KB

SRI International Bioinformatics Naming Frames Use names with biological meaning Recommendation: do not change names if they have been in use for more than 1 hour Conventions: l hyphens as word separators l name length is restricted to 40 characters l instance names are written in uppercase l most class names are capitalized (e.g, Compounds) - use |

SRI International Bioinformatics Naming Conventions Compounds: mnemonics, others with prefix C Genes: use same id as genome project Polypeptides: use mnemonic plus suffix -MONOMER Protein complexes: use mnemonic plus suffix -CPLX Enzymatic reactions: use mnemonic plus suffix -ENZRXN Reactions: use mnemonic or EC number plus suffix -RXN Pathways: use mnemonic plus suffix -PWY

SRI International Bioinformatics Pathway Editor To graphically create and modify pathways Two tools: l Connections Editor: to add reactions, remove reactions, alter connections l Always invoked first l Segment Editor: to enter a linear pathway segment Invoking the pathway editor: New: Special => Create Pathway or Edit New Pathway in Pathway Mode Existing: Right-Click menu for pathway, select Pathway Editor command

SRI International Bioinformatics Connections Editor Operations Two main display panes: l left: unconnected pathway reactions l right: draws connected reactions (looks like the regular Pathway Tools window) Connecting reactions: l select initial reaction (in either pane) ===> red and green reactions l select a green reaction Additional Commands: l Exit: keep changes, abort changes l Reaction: add reaction, add reaction(s) from history, create new reaction frame, clone a reaction frame, add connection, delete predecessor/successor link, disconnect reaction, delete reaction from pathway, choose main compounds for reaction, edit reaction frame l Pathways: enter a linear pathway segment, guess pathway predecessor list, disconnect all reactions, invoke relationships editor, add subpathway by name, add subpathway by substring, add subpathway by class, delete subpathway

SRI International Bioinformatics Connections Editor Limitations Ambiguity in some complicated situations on ordering: l link may be ignored l dialog box for disambiguating l pathway drawn in bizarre arrangement Fix: l try removing offending link and add links in different order Pathway editor does not handle polymerization pathways Pathway editor does not permit specification (for a circular pathway) which compound should be on top

SRI International Bioinformatics Pathway Segment Editor To enter linear sequence of reactions faster than with the Connections Editor Reactions are specified by EC numbers or reaction substrates One segment may contain up to 7 reactions

SRI International Bioinformatics Reaction Editor To create a new reaction frame in a P/G database Contains Compound Resolver Can automatically create enzymatic-reaction and protein frames and their relationship links Invoke by: Create Reaction from Reaction Mode Entering Reaction Equation: Reaction frame id, Reaction EC number, Reaction equation, Enzymatic-Reaction frame id, Enzymatic-Reaction names, Protein Complex?, Protein Frame id, Protein names, Show rxn, Edit rnx frame, Balanced?, Done, Abort Compound Resolution Tool

SRI International Bioinformatics Citations I May be stored in Citations slot of objects: l As a single value (e.g., [SMITH95] or [ ] (Medline UID)) May be attached to specific slot values: l By putting citation in an annotation called CITATION May be placed within the text in a COMMENT slot l Example text: The subunit structure of this enzyme was determined by Jones and colleages |CITS: [ ]|.

SRI International Bioinformatics Citations II Creating Publications Frames l Special => Hierarchy Viewer l Frame => Find Publications l Frame => Create => Instance l Frame => Edit

SRI International Bioinformatics Creating Links with External Databases Object Correspondence Creating links to a pathway/genome db Creating links from a pathway/genome db

SRI International Bioinformatics Ocelot Concurrency Control I Simultaneous updates Optimistic concurrency control l optimistic: assumes conflicts will be infrequent l allows users to make changes at will l checks for conflicts at times of saving

SRI International Bioinformatics Ocelot Concurrency Control II Save KB operation l 1. Ocelot checks whether any changes made by user conflict with changes that may have been saved recently by others l 2. No conflicts found => save to Oracle Saves to current organism KB Unsaved KB indicator (*)

SRI International Bioinformatics Ocelot Concurrency Control III Revert KB operation Refresh KB operation l automatically at 2:00 am u if the user does not have any unsaved updates in their wokspace

SRI International Bioinformatics Editing rules: Support Policy Do not alter KB schema l e.g. do not add or remove classes or slots Do not modify the E. coli or MetaCyc datasets

SRI International Bioinformatics The Special Menu: KB Show KB Modifications Revert KB Refresh KB Reconnect to Oracle Checkpoint KB Restore Checkpoint Delete KB

SRI International Bioinformatics Constraint Checking General rules that constrain the valid relationships among instances Constraints are checked when new facts are asserted to assure that the KB remains logically consistent Constraints on slots: l Domain violation checks to make sure they should be in instances of that class l Range violation : u value type u value cardinality l Inverse l Cardinality l Lisp-predicate

SRI International Bioinformatics Consistency Checking Removes newlines from names Converts < to | in string citations Check isozyme sequence similarity Fix references from polypeptides to genes Changes compound names to ids in a variety of slots Matches physiological regulators to other regulators Cross-references compounds to reactions Checks pathways predecessors/reactions/subs Check reactions Check compound structures Calculates sub- and super-pathways Finds missing sub-pathways links Verifies chromosome components and positions