Transcript Introduction - Bioinformatics Research Group at SRI International

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Editing Pathway/Genome
Databases
Ron Caspi
Part I: Compounds, Reactions and Pathways
Why Curation is Important!
 Database
curation greatly enhances the
usefulness of the data
 “in
silico” information less solid than
experimental evidence
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Pathway Tools Paradigms
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Separate database from user interface
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Navigator provides one interface to the DB
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Editors provide an alternative interface to the DB
• Reuse information whenever possible!
• A PGDB should not describe the same biological or chemical
entity more than once
• Compounds are the building blocks of reactions
• Reactions are the building blocks of pathways
List of Editors
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Compound Editor
Compound Structure Editor
Reaction Editor
Pathway Editor
Synonym Editor
Protein Editor
Gene Editor
Intron Editor (Eukaryotes only)
Transcription Unit Editor
Publication Editor
Frame Editor
Relationships Editor
Ontology Editor
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Invoking the Editors
Use the “New” command
Or: Right-Click on an
Object Handle
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Saving Changes
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user must save changes explicitly with Save DB
discard changes made since last save
 File => Revert Current DB
The File Menu: DB commands
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List Unsaved Changes in Current DB
Revert Current DB
Refresh All Current DBs
Checkpoint Current DB
Revert to Checkpoint in Current DB
Delete a DB
Save Current DB
Attempt to Reconnect to Oracle
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Editing rules: Support Policy
 Do
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not alter DB schema
 e.g. do not add or remove classes or slots
 Do not modify the EcoCyc or MetaCyc datasets
Compound Editor
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Create or edit a
compound
Invoke by:
New:
Compound => New
Existing: Right-Click compound
name, select Compound Editor
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Common name and
synonyms
links to other DBs
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More Compound Editing
 Compound
 Mol
Structure Editor
files
 Exporting to other DBs
 Merging
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Reaction Editor
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Create or edit a reaction
Invoke by:
New:
Reaction => New
Existing: Right-Click reaction name, select Reaction Editor
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Entering Reaction Equation
Compound Resolver
Pathway Editor
 Graphically
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create and modify pathways
 Two
tools:
 Connections Editor: to add reactions, remove reactions, alter
connections
 Segment Editor: to enter a linear pathway segment(s)
 Invoking
the pathway editor:
New:
Pathway => New
Existing: Right-Click pathway name,
select Pathway Editor command
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Connections Editor Operations
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Two main display panes:
 left: unconnected pathway reactions
 right: draws connected reactions (looks like the regular Pathway Tools
window)
Connecting reactions:
 select initial reaction (in either pane) ===> red and green reactions
 select a green reaction
Additional Commands:
 Exit: keep changes, abort changes
 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
 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
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Connections Editor Limitations
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Ambiguity in some complicated situations on ordering:
 link may be ignored
 dialog box for disambiguating
 pathway drawn in bizarre arrangement
Fix:
 try removing offending link and add links in different order
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Pathway editor does not handle polymerization pathways
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In circular pathways, Pathway editor does not permit
specification which compound should be at the top
Pathway Segment Editor
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 To
enter linear sequence of reactions (arguably)
faster than with the Connections Editor
 Reactions
are specified by EC numbers or
reaction substrates
 One
segment may contain up to 7 reactions
Creating Links with External
Databases
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Creating links from a pathway/genome db to an external
database
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To define a new external database:
Tools => Ontology Browser
View => Browse from new root / type Databases
Highlight Databases
Frame => Create => Instance
Enter frame name, frame edit
Enter Common Name, Static-Search-URL
e.g. http:/gene.pharma.com/dbquery?
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Creating links to a pathway/genome db
see http://biocyc.org/linking.shtml
Make sure that…
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You perform all exercises
on the Hb. pylori database,
not on your own!!!
Creating New Reactions
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Create the following five reactions:
1.
ascorbate + H2O = 3-keto-L-gulonate
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3-keto-L-gulonate + ATP = 3-keto-L-gulonate-6-phosphate + ADP
3.
3-keto-L-gulonate-6-phosphate = L-xylulose-5-phosphate + CO2
4.
L-xylulose-5-phosphate = L-ribulose-5-phosphate*
5.
L-ribulose-5-phosphate = xylulose-5-phosphate
Create a New Compound
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Define a New Pathway
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Define the pathway L-ascorbate degradation to xylulose-5phosphate by connecting the reactions together
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Assign class:
(Pathways -> Degradation/Utilization/Assimilation -> Carboxylates,
Other)
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Add a link to non-oxidative branch of the pentose phosphate
pathway
(Generation of precursor metabolites and energy => Pentose
phosphate pathways =>)
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Add a reverse link from non-oxidative branch of the pentose
phosphate pathway to the new pathway
Pathway Curation
• Class
• Common Name
• Synonyms
• Evidence code
• Citations
• Comments
• Links
• Hypothetical
reactions
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Evidence Codes for Pathways
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http://brg.ai.sri.com/ptools/evidence-ontology.html
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EV-AS: Author statement
 NAS – non-traceable
 TAS - traceable
EV-COMP: Inferred from computation
 AINF - Artificial inference
 HINF - Human inference
EV-EXP: Inferred from experiment
 IDA - inferred from direct assay
 IEP - inferred from expression pattern
 IGI - inferred from genetic interaction
 IMP- inferred from mutant phenotype
 IPI - inferred from physical interaction
EV-IC: Inferred by curator
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Super Pathways
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 Create
more complex metabolic networks using
superpathways
 Example:
superpathway of alanine biosynthesis
composed of alanine biosynthesis I
alanine biosynthesis II
alanine biosynthesis III
Pathway Export
 Export
Edit => Add Pathway to File Export List
 File => Export => Selected Pathways to File
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Constraint Checking
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General rules that constrain the valid relationships among
instances
Constraints are checked when new facts are asserted to
assure that the DB remains logically consistent
Constraints on slots:
 Domain violation checks to make sure the slots are in instances of the
appropriate class
 Range violation :
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value type
value cardinality
Inverse
Cardinality
Lisp-predicate
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Consistency Checking (correctify-kb)
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Removes newlines from names
Converts “<“ to “|” in string citations
Checks isozyme sequence similarity
Fixes 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
Checks reaction balancing
Checks compound structures
Calculates sub- and super-pathways
Finds missing sub-pathways links
Verifies chromosome components and positions
Run (correctifykb)
 Open
 Run
the database Hb. pylori (HypCyc)
(correctify-kb)
 Analyze
output
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