Editing Pathway/Genome Databases

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Editing Pathway/Genome Databases
Ron Caspi
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Pathway Tools in Editing Mode

• The database is separate from the user interface
• The Navigator provides one interface to the DB
• Editors provide an alternative interface to the DB

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Things to remember

• The editors are there for editing your own PGDB.
  Do not modify the EcoCyc or MetaCyc datasets
• Try to not alter the DB schema. Such changes may
  be overwritten when updating to a new version
• e.g. do not add or remove classes or slots
• Avoid Duplication! Reuse information whenever
  possible
• A PGDB should not describe the same biological or
  chemical entity more than once
• Some tools help preventing inadvertent creation
  of duplicate reactions/compounds

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List of Editors

• Compound Editor/Compound Structure Editors
• Reaction Editor
• Pathway Editor and Pathway Info Editor
• Protein/Subunit structure/Enzymatic Reaction
  Editors
• Synonym Editor
• Publication Editor
• Author/Organization Editor
• Gene Editor
• Intron Editor (Eukaryotes only)
• Transcription Unit Editor
• External database Editor
• Frame Editor
• Ontology Editor

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Activating Editing Mode

• Type (enable/disable-editors t) at the listener
  pane

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Saving Changes

• The user must save changes explicitly
• File gt Save Current DB
• Save DB button
• Revert Current DB
• The following commands are only available for
  databases stored in MySQL or Oracle
• List Unsaved Changes in Current DB
• Checkpoint Current DB Updates to File
• Restore Updates from Checkpoint File

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Other DB commands under the File menu

• Summarize databases
• Summarize current organism
• Refresh DB list
• Refresh All Current DBs
• Delete a DB
• Attempt to Reconnect to Database Server

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Invoking the Editors

• New Object Use the New command under top
  menus, or the Create command under the File
  menu (new feature)
• Existing Object Right-Click on the Object
  Handle, select Edit, then the appropriate editor

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Compound Editor

• Create or edit a compound
• Specify Class
• Common Name and Synonyms
• Comments, citations
• Links to other DBs

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More Compound Editing

• Compound Structure Editors (Marvin, JME)
• http//www.chemaxon.com/marvin/index.html
• Export/Import to Mol files
• Exporting to other DBs
• Merging
• Duplicate Frame and Edit

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The Synonym Editor

• Lets you easily edit the synonyms and set the
  common name

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Reaction Editor

• Enter or edit a reaction
• equation
• Set Conversion Type
• EC number (official?)
• Compartments (transport)
• Create new instances or classes

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Pathway Info Editor

• Class (variant class)
• Common Name
• Synonyms
• Evidence Codes
• Citations (CIT)
• Summary
• External Links
• Hypothetical reactions
• Enzymes not in use
• Author credits

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Evidence Codes for Pathways

• http//bioinformatics.ai.sri.com/evidence-ontology
  /
• 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
• Full documentation for an evidence code is
  displayed in the Navigator (click the code icon)

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Pathway Editor

• Graphically create and modify pathways
• Reaction Menu
• add reactions one by one
• Pathway Menu
• enter a linear pathway segment, add
  subpathways

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Connections Editor Operations
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Pathway Editor Limitations

• Complex situations can cause ambiguity
• link may be ignored
• dialog box for disambiguating
• pathway drawn in bizarre arrangement
• Fix
• try removing offending link and add links in
  different order
• The Pathway Editor does not handle polymerization
  pathways easily.

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Overview of Creating a Pathway

• Identify all the metabolites. Define any missing
  ones.
• Find the individual reactions in the
  PGDB/MetaCyc, and create new reactions if
  necessary.
• Compose the pathway from the individual reactions
  using the pathway editor
• Assign a class for the pathway
• Add a summary, citations, and evidence code
• Assign the appropriate enzymes, create complexes
  when appropriate.
• Curate information about enzymes and genes,
  including evidence codes for all enzymes.

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• Tutorial Compounds, Reactions and Pathways

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Import MetaCyc reactions instead of creating
duplicates!

• If the reaction is already present in MetaCyc,
  you will see a window like this one
• You should choose the option Import. However,
  you MUST write down the frame ID of the identical
  reaction, so you could use it later when
  specifying the pathway.

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Reuse existing reactions instead of creating
duplicates!

• If the reaction is already present in your PGDB,
  you will see a window like this one
• You should choose the option Delete. However,
  you MUST write down the frame ID of the identical
  reaction, so you could use it later when
  specifying the pathway.

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Fill Reaction frame IDs in your handout
Reaction Frame ID
ascorbate H2O 3-keto-L-gulonate RXN0-707

3-keto-L-gulonate ATP 3-keto-L-gulonate 6-phosphate ADP

3-keto-L-gulonate 6-phosphate L-xylulose-5-phosphate CO2

L-xylulose-5-phosphate L-ribulose-5-phosphate

L-ribulose-5-phosphate xylulose-5-phosphate

xylulose-5-phosphate D-ribulose-5-phosphate
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Creating New Reactions

• Dont forget to include spaces between chemical
  names and terms such as and
• ascorbate H2O 3-keto-L-gulonate
• 3-keto-L-gulonate ATP 3-keto-L-gulonate-6-phos
  phate ADP
• 3-keto-L-gulonate-6-phosphate
  L-xylulose-5-phosphate CO2
• L-xylulose-5-phosphate L-ribulose-5-phosphate
• L-ribulose-5-phosphate xylulose-5-phosphate
• xylulose-5-phosphate D-ribulose-5-phosphate

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Curating Enzymes
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Adding an Enzyme to a Reaction

• To add an enzyme to a reaction
• Right click the reaction, choose Edit ?
  Create/Add enzyme.
• If the enzyme exists, specify its ID. If not,
  click Search by genes or create new protein
• The Protein Subunit Structure Editor pops up

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Specifying Enzyme Complexes
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Specifying Multiple Subunits
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The Enzyme Editor
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Protein Editor
For an example, open CPLX-6621 in MetaCyc
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Enzymatic Reaction Editor
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Protein Subunit Editor

• Specify the copy number of each subunit
• Specify UniProt ID if available, experimental MW,
  and any useful info that may apply

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Citations

• Citation boxes
• The CITS field
• File gtImport Citations from PubMed
• Publication editor (invoke by right clicking on
  a citation at bottom)

Non PubMed citation Enter in citation box in the
form Smith06, invoke editor by clicking out of a
citation box.
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• Tutorial Enzymes, citations and export