Introduction - Bioinformatics Research Group at SRI International
Download
Report
Transcript Introduction - Bioinformatics Research Group at SRI International
Update your computers!
To
SRI International
Bioinformatics
install a patch:
Tools => Instant Patch => Download and Activate
All Patches
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
SRI International
Bioinformatics
Pathway Tools Paradigms
SRI International
Bioinformatics
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
List 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 International
Bioinformatics
Invoking the Editors
Use the “New” command
Or: Right-Click on an
Object Handle
SRI International
Bioinformatics
Saving Changes
The
To
SRI International
Bioinformatics
user must save changes explicitly with Save DB
discard changes made since last save
File => Revert Current DB
The 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 International
Bioinformatics
Editing rules: Support Policy
Do
SRI International
Bioinformatics
not alter DB schema
e.g. do not add or remove classes or slots
Do not modify the EcoCyc or MetaCyc datasets
Compound 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 International
Bioinformatics
More Compound Editing
Compound
Mol
Structure Editor
files
Exporting to other DBs
Merging
SRI International
Bioinformatics
Reaction Editor
SRI International
Bioinformatics
Create or edit a reaction
Invoke by:
New:
Reaction => New
Existing: Right-Click reaction name, select Reaction Editor
Entering Reaction Equation
Compound Resolver
Pathway Editor
Graphically
SRI International
Bioinformatics
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
SRI International
Bioinformatics
Connections 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 International
Bioinformatics
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
Pathway Segment Editor
SRI International
Bioinformatics
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
SRI International
Bioinformatics
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 db
see http://biocyc.org/linking.shtml
Make sure that…
SRI International
Bioinformatics
You perform all exercises
on the Hb. pylori database,
not on your own!!!
Creating New Reactions
SRI International
Bioinformatics
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
Create a New Compound
SRI International
Bioinformatics
Define a New Pathway
SRI International
Bioinformatics
Define the pathway L-ascorbate degradation to xylulose-5phosphate 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
Pathway Curation
• Class
• Common Name
• Synonyms
• Evidence code
• Citations
• Comments
• Links
• Hypothetical
reactions
SRI International
Bioinformatics
Evidence Codes for Pathways
SRI International
Bioinformatics
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
Super Pathways
SRI International
Bioinformatics
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
SRI International
Bioinformatics
Constraint Checking
SRI International
Bioinformatics
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 International
Bioinformatics
Consistency 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
Run (correctifykb)
Open
Run
the database Hb. pylori (HypCyc)
(correctify-kb)
Analyze
output
SRI International
Bioinformatics