1. The Pathway/Genome Navigator

2. Overview Data page types General query strategies Web queries
Desktop Pathway Tools
User preferences
Lab exercises

3. Pathway/Genome Navigator
Navigator runs both on the desktop and on the web
Desktop version
Runs faster
More capabilities
PGDB creation, editing
Reachability analysis, metabolite tracing, object groups
More omics analysis
Both have capabilities the other does not have

4. Data Page Types for Individual PGDB Objects
Genes*
RNAs *
Proteins *
Enzymes, transporters, transcription factors, others
Extensive comments and citations
Monomers and multimers are represented, and in different chemical states
Transcription units
Reactions
Pathways
Compounds
Organisms
Searches are organized around these page types
* Note: Gene pages will be merged with RNA and Protein pages in early 2010

5. Direct Queries Search for a specific object you know
Searches common to all object types
By name – must be exact (though there are synonyms)
By identifier
BioCyc ID
Accession number
Web only: UniProt ID
By substring – if you don’t know an exact name
Searches that are specific to object type

6. Indirect Queries
Find an object by searching for an object that is probably related to it
Then navigate to the object you seek

7. Complex Queries Define multi-criteria searches
System returns all objects that meet those criteria

8. BioCyc Web Site Web browsers Firefox Safari Chrome
Internet Explorer not recommended
Create a Web account
Save page formatting preferences, omics viewer preferences
Save default organism
Save organism lists for comparative analyses
Receive updates on new releases

9. Web Searches
Multiple searches available for finding information in different ways
Quick search (simplest search)
Object-specific searches
Ontology-based searches
Advanced search
Searches of full-text literature articles

10. Select Current Organism
Click on “change”
Under Quick Search button
Bottom of Search menu
Bottom of Tools menu
Select by typing or clicking

11. Organism Pages Tools -> Reports -> Summary statistics
PGDB authors, statistics

12. Sample Web Searches for EcoCyc
Quick Search: xyl
Quick Search: trpa type:gene
Quick Search: b1200
Search -> Genes/Proteins/RNAs
40 < MW < 50 and 5.5 < pI < 6.0
< Map-Position < and
Has Gene Ontology term “locomotion”
(under Biological Process)

13. Sample Web Searches for HumanCyc
Quick Search: dopamine
Quick Search: dopamine type:compound
Quick Search: b1200
Search -> Genes/Proteins/RNAs
Enzymes using Mg2+ as a cofactor
Search -> Compounds
300 <= MW <= and containing N

14. Shared Display Characteristics
Gene-Reaction schematic
Citations and comments
Database Links
Classes

15. Gene-Reaction Schematic
Drawn in reaction, protein, and gene windows
Representations (ArgB)
Genes are boxes on the right
Proteins are circles in the middle – numbers show complexes
Reactions in box on left, with E.C. number if available
Allows navigation between genes, proteins, rxns
Links proteins with shared reactions
ArgD
Links members of protein complexes
Pol III – extreme example

16. Citations and Comments
Citations in mnemonic form
Click on citation – go to citations at bottom of page
Click there, go to PubMed ref, if available

17. Database Links Unification links (info about the protein elsewhere)
PDB
PIR
RefSeq
UniProt
Relationship links:
PDB-Homolog-P34554

18. Class Hierarchies Reactions
Enzyme-nomenclature system (full EC system in MetaCyc only)
Proteins
Gene Ontology terms are assigned to proteins
Can also assign MultiFun terms
Compounds
Pathways

19. Desktop Mode

20. Desktop Mode
Linux/PC, Windows/PC, Macintosh

21. Desktop Window Layout One Large Window Several Panes: Display pane
Command menu
LISP listener

22. Menus Main command menu Single-choice menu
Multiple-choice menu (e.g. after a search)
Aborting out of menus
Click Cancel or No Select
Click outside the menu
Type ^z

23. Using the Mouse
Left mouse button: to invoke specific commands and for hypertext navigation
Right mouse button: to bring up menus of additional operations (for example, when editing a frame)
Mouse documentation line (shows what you’re over, what you can do)

24. Queries with Multiple Answers
Results in form of a menu to:
select one
some
all
Answer List
Next Answer

25. Organism Pages All Organisms Page – Starting Page Organism grouping
Summary of organisms
Single organism page
PGDB authors, statistics

26. Select Current Organism
From All Organisms Page
Through organism selector

27. Pathway Mode Commands Search by pathway name Search by substring
Search by class
Search by substrates (can pick role in pathway)

28. What’s in a Pathway Frame?
Go to arginine biosynthesis I (from ArgD)
Intermediates and reactions
Can toggle level of detail
Feedback regulation can be shown
Locations of mapped genes
Genetic regulation schematic
Note presence of comments, citations, class hierarchy

29. Reaction Mode Commands
Search by reaction name
Search by E.C. #
Search by class (another E.C. interface)
Search by pathway
Search by substrates

30. What’s in a Reaction Frame?
Search by EC for (pick one)
Picture of reaction with clickable compounds
Pathways the reaction is involved in
Place in class hierarchy
Enzymes carrying out reaction (note schematic)

31. Protein Mode Commands Search by protein name Search by substring
Search by pathway
Search by organism (MetaCyc)
Search by UniProt Acc
Search by GO term
Search by MultiFun term
Search by Weight, pI
Search by modulation of activity

32. What’s in a Protein Frame?
Sample frame (ArgD)
Synonyms, general features, comments
Unification links, gene-reaction schematic
GO terms
Enzymatic reaction frames – how this protein carries out that reaction (bridging the two)
Evidence codes

33. Gene Mode Commands Search by gene name (can also put in TU IDs)
Search by substring
Get gene by class
Basically the same for RNAs

34. What’s in a Gene Frame? Sample frame (argC)
Synonyms, classification (GO), link to browser
Unification links, gene-reaction schematic
Regulation schematic
Gene local context and TUs

35. What’s in a Transcription Unit Frame?
Sample frame (argCBH)
Genes in context, with TFs
Promoter with start site and citations
TF binding sites, with citations
Regulatory interactions (ilvL attenuator in TU524)

36. Compound Mode Commands
Search compound by name
Search compound by substring
Search by SMILES (structure)
Search by class
Advanced search

37. The SMILES Language Simplified Molecular Input Line Entry System
Formal language for describing chemical structures
Used within the Pathway Tools in a substructure search
Case is significant (lowercase for aromatic rings)
Examples:
formate C(=O)O
malate OC(=O)CC(O)C(O)=O
For more information, see the Help facility

38. What’s in a Compound Frame?
Sample (N-acetylglutamyl-phosphate)
Synonyms, empirical formula, MW, links
Structure
SMILES code
Pathways and reactions involving this compound

39. Miscellaneous Commands
History commands
Answer-List commands
Clone window command
Fix window and unfix window commands
Other commands:
Print to file (makes a postscript)
Help
Preferences
Exit

40. History List
Backward history
Forward history
Select from history

41. User Preferences Color Layout Compound window Reaction window
Pathway window
History/Answer list
Reverting and saving user preferences

42. Program-Based Queries
Write queries in LISP
Must understand features of schema
class names
slot names
Pathway tools site has example searches
Definitely learnable
Can place results on the answer list

43. Lab Exercises Set up personal preferences for: Color
Layout (set number of windows to 2)
Save new preferences
Play with settings for Compound, Reaction, Pathway, and Overview windows.
Choose settings for History/Answer List preferences

44. Lab Exercises Retrieve compounds containing a formate group
Retrieve compounds adenine and uracil using class query
Retrieve reaction with EC#
Retrieve all reactions in the class sulfurtransferases
Retrieve all reactions involved in proline biosynthesis
Retrieve all reactions where glutamate appears on left side
genes coding for enzymes involved in the degradation of short-chain fatty acids

45. Lab Exercises Retrieve all enzymes involved in purine biosynthesis
Retrieve all kinases
Display region spanning from 10 % - 20 % of E. coli chromosome
Display chromosomal region around gene aroA
Display a map showing all chaperone genes

46. Lab Exercises Retrieve all chaperone genes Retrieve gene aroA
Find the glutamine biosynthesis pathway by issuing each of the three types of queries in Pathway mode.

47. Lab Exercises Clone window Navigate in the cloned window
Set preferences so Navigator displays 2 windows
Navigate by clicking on live objects
Fix Window
Navigate in unfixed window
Fix second window and then click on live object