The Pathway/Genome Navigator

1
The Pathway/Genome Navigator

• (These slides are a guide as you experiment with
  the Navigator)

2
Pathway/Genome Navigator topics

• Getting started with the Navigator
• Organism pages
• Queries in general
• Object displays and queries
• Miscellaneous commands
• User preferences
• Lab exercises

3
Introduction

• Navigator runs both on the desktop and on the web
• The desktop version generally has more
  capabilities

4
Desktop Layout

• One Large Window
• Several Panes
• Display pane
• Command menu
• LISP listener

5
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

6
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)
• Middle mouse button for very specialized uses
  (you probably wont use it)
• Mouse documentation line (shows what youre over,
  what you can do)

7
Organism Pages

• All Organisms Page
• Organism grouping
• Summary of organisms
• Single organism page
• Summary of organism stats
• Notion of current organism
• Command mode queries
• Comparative analyses
• Clicking through links organism continuity

8
Query Facilities topics

• Direct queries
• Queries with multiple answers
• Indirect approach navigation
• History List
• Complex queries

9
Direct Queries

• Done by type (for example, search for proteins)
• Searches common to all types
• By name/frame ID must be exact (though there
  are synonyms)
• By substring if you dont know an exact name
• Particular searches by type
• Will be handled as we cover each type

10
Queries with multiple answers

• Results in form of a menu to
• select one
• some
• all
• Answer List
• Next Answer

11
Indirect Queries

• Related objects
• Objects are clickable
• Objects are color-coded by type

12
History List

• Backward history
• Forward history
• Select from history

13
Complex Queries

• WWW Form
• 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

14
Object Displays and Queries topics

• Shared display characteristics
• Searching within each category of object
• Whats in each kind of object frame?
• Looking at genomes and orthologs

15
Shared Display Characteristics

• Gene-Reaction schematic
• Citations and comments
• Database Links
• Classes

16
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

17
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

18
Database Links

• Unification links (info about the protein
  elsewhere)
• PDB
• PIR
• RefSeq
• UniProt
• Gene page For coli, we added links to
  coli-specific sites
• Relationship links
• PDB-Homolog-P34554

19
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

20
Menu Categories

• Pathway
• Reaction
• Protein
• (RNA)
• Gene
• Compound

21
Pathway Mode Commands

• Search by pathway name
• Search by substring
• Search by class
• Search by substrates (can pick role in pathway)

22
Whats 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

23
Reaction Mode Commands

• Search by reaction name
• Search by E.C.
• Search by class (another E.C. interface)
• Search by pathway
• Search by substrates

24
Whats in a reaction frame?

• Search by EC for 2.6.1.11 (pick one)
• Picture of reaction with clickable compounds
• Pathways the reaction is involved in
• Place in class hierarchy
• Enzymes carrying out reaction (note schematic)

25
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

26
Whats 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

27
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

28
Whats 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

29
Whats in a TU 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)

30
Compound Mode Commands

• Search compound by name
• Search compound by substring
• Search by SMILES (structure)
• Search by class
• Advanced search

31
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

32
Whats in a compound frame?

• Sample (N-acetylglutamyl-phosphate)
• Synonyms, empirical formula, MW, links
• Structure (you can add these in editors)
• SMILES code
• Pathways and reactions involving this compound

33
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

34
User Preferences

• Color
• Layout
• Compound window
• Reaction window
• Pathway window
• History/Answer list
• Reverting and saving user preferences

35
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

36
Lab Exercises

• Retrieve compounds containing a formate group
• Retrieve compounds adenine and uracil using class
  query
• Retrieve reaction with EC 5.3.1.9
• 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

37
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

38
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.

39
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