Advanced Editing of Pathway/Genome Databases

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Advanced Editing of Pathway/Genome Databases
Ron Caspi
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General Curation
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User Preferences
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Create and Use Author and Organization Frames
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Using the Text Editor

• Formatting
• ltigtitaliclt/igt, ltbgtboldlt/igt
• know your alpha, beta
• 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
  CITSPMID1PMID2 (rather than CITSPMID1,
  CITSPMID2.
• Special characters
• Ångstrom Aring (Å)
• Degree deg (?)

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Use Internal Hyperlinks
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Use Variant Classes
example Putrescin Biosynthesis
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Hypothetical Reactions, Excluded Enzymes
Specified in the Pathway Info Editor

• 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 2.1.3.3, ornithine carbamoyltransferase)
• Hypothetical reactions useful when a pathway
  step is proposed, but has not been proven

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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)
• is composed of
• catechol degradation II
• mandelate degradation I
• benzoate degradation (aerobic)
• b-ketoadipate degradation
• protocatechuate degradation II
• shikimate degradation
• quinate degradation
• 4-hydroxymandelate degradation
• tryptophan degradation I

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Advanced Curation
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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

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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
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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

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Converting an existing compound instance to a
class
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!

• 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

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The Ontology Editor
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The Ontology Editor

• Changing parent classes
• Adding parent classes
• Creating new classes to improve ontology
• Tutorial the Ontology Editor

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The Consistency Checker
Consistency Checking should be performed
routinely (every few months), and detected
problems should be addressed
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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.
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Consistency Checker Manual Tasks
Example create an empty FRAME construct,
then run the task Check Frame References
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Exporting Pathways Between PGDBs

• To export a pathway to a file
• (optional inclusion of enzymes and genes)
• Edit gt Add Pathway to File Export List
• File gt Export gt Selected Pathways to
  Lisp-format File
• To import a pathway from file
• File gt Import gt Pathways from File
• To export a pathway directly to another PGDB
  (both PGDBs must be installed on the same
  system)
• Edit -gt Export Pathway to DB

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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))

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Exporting Graphics

• You can save any screen as a vector-based
  postscript file by using File -gt 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.

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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 http//biocyc.org/linking.shtml

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External Database Editor
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Polymerization
example folate polyglutamylation I
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The Pathway Registry
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The Registry Schema Upgrades
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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