sri international bioinformatics update your computers! to install a patch: tools => instant...
TRANSCRIPT
SRI InternationalBioinformaticsUpdate your computers!
To install a patch:
Tools => Instant Patch => Download and Activate All Patches
Editing Pathway/Genome Databases
Part I: Compounds, Reactions and Pathways
Ron Caspi
SRI InternationalBioinformaticsWhy Curation is Important!
Database curation greatly enhances the usefulness of the data
“in silico” information less solid than experimental evidence
SRI InternationalBioinformaticsPathway Tools Paradigms
Separate database from user interface
Navigator provides one interface to the DB
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
SRI InternationalBioinformaticsList of Editors
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
SRI InternationalBioinformaticsInvoking the Editors
Or: Right-Click on an
Object Handle
Use the “New” command
SRI InternationalBioinformaticsSaving Changes
The user must save changes explicitly with Save DB
To discard changes made since last save File => Revert Current DB
SRI InternationalBioinformaticsThe File Menu: DB commands
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
SRI InternationalBioinformaticsEditing rules: Support Policy
Do not alter DB schema e.g. do not add or remove classes or slots
Do not modify the EcoCyc or MetaCyc datasets
SRI InternationalBioinformaticsCompound Editor
Create or edit a compound
Invoke by:
New: Compound => New
Existing: Right-Click compound name, select Compound Editor
Common name and synonyms
links to other DBs
SRI InternationalBioinformaticsMore Compound Editing
Compound Structure EditorMol filesExporting to other DBsMerging
SRI InternationalBioinformaticsReaction Editor
Create or edit a reaction Invoke by:
New: Reaction => New
Existing: Right-Click reaction name, select Reaction Editor
Entering Reaction Equation Compound Resolver
SRI InternationalBioinformaticsPathway Editor
Graphically 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 => NewExisting: Right-Click pathway name,
select Pathway Editor command
SRI InternationalBioinformaticsConnections Editor Operations
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
SRI InternationalBioinformatics
Connections Editor Limitations
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
Pathway editor does not handle polymerization pathways
In circular pathways, Pathway editor does not permit specification which compound should be at the top
SRI InternationalBioinformaticsPathway Segment Editor
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
SRI InternationalBioinformaticsCreating Links with External
Databases
Creating links from a pathway/genome db to an external database
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?
Creating links to a pathway/genome dbsee http://biocyc.org/linking.shtml
SRI InternationalBioinformaticsMake sure that…
You perform all exercises on the Hb. pylori database, not on your own!!!
SRI InternationalBioinformaticsCreating New Reactions
Create the following five reactions:
1. ascorbate + H2O = 3-keto-L-gulonate
2. 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
SRI InternationalBioinformaticsCreate a New Compound
SRI InternationalBioinformaticsDefine a New Pathway
Define the pathway L-ascorbate degradation to xylulose-5-phosphate by connecting the reactions together
Assign class:
(Pathways -> Degradation/Utilization/Assimilation -> Carboxylates, Other)
Add a link to non-oxidative branch of the pentose phosphate pathway(Generation of precursor metabolites and energy => Pentose phosphate pathways =>)
Add a reverse link from non-oxidative branch of the pentose phosphate pathway to the new pathway
SRI InternationalBioinformaticsPathway Curation
• Class
• Common Name
• Synonyms
• Evidence code
• Citations
• Comments
• Links
• Hypothetical reactions
SRI InternationalBioinformaticsEvidence Codes for Pathways
http://brg.ai.sri.com/ptools/evidence-ontology.html
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
SRI InternationalBioinformaticsSuper Pathways
Create more complex metabolic networks using superpathways
Example: superpathway of alanine biosynthesis
composed of alanine biosynthesis I
alanine biosynthesis II
alanine biosynthesis III
SRI InternationalBioinformaticsPathway Export
Export
Edit => Add Pathway to File Export List File => Export => Selected Pathways to File
SRI InternationalBioinformaticsConstraint Checking
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 :
value type value cardinality
Inverse Cardinality Lisp-predicate
SRI InternationalBioinformaticsConsistency Checking
(correctify-kb) 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
SRI InternationalBioinformaticsRun
(correctify-kb)
Open the database Hb. pylori (HypCyc)
Run (correctify-kb)
Analyze output