The Pathway/Genome Navigator
(These slides are a guide as you
experiment with the Navigator)
SRI International
Bioinformatics
Pathway/Genome Navigator – topics
 Getting
started with the Navigator
 Organism pages
 Queries in general
 Object displays and queries
 Miscellaneous commands
 User preferences
 Lab exercises
Introduction
 Navigator
SRI International
Bioinformatics
runs both on the desktop and on the
web
 The
desktop version generally has more
capabilities, but each has unique features
Desktop Mode -- Introduction
SRI International
Bioinformatics
Desktop Layout
 One
Large Window
 Several
Panes:
 Display pane
 Command menu
 LISP listener
Desktop Menus
 Main
SRI International
Bioinformatics
command menu
 Single-choice
menu
 Multiple-choice
 Aborting
menu (e.g. after a search)
out of menus
 Click Cancel or No Select
 Click outside the menu
 Type ^z
Using the Mouse
SRI International
Bioinformatics
 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 won’t use it)
 Mouse
documentation line (shows what you’re
over, what you can do)
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
SRI International
Bioinformatics
SRI International
Bioinformatics
Queries with multiple answers
 Results
in form of a menu to:
 select one
 some
 all
 Answer
List
 Next Answer
Indirect Queries
 Related
objects
 Objects
are clickable
 Objects
are color-coded by type
SRI International
Bioinformatics
History List
 Backward
 Forward
 Select
history
history
from history
SRI International
Bioinformatics
SRI International
Bioinformatics
Writing Complex Queries
 Web
Search  Advanced
 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

Using the BioCyc Web Site
and Other
Pathway Tools Based Web Sites
BioCyc Searches
SRI International
Bioinformatics

Multiple searches available for finding information in different
ways
The easiest searches to use are fairly coarse

Start by selecting database to search

Simplest search: Quick Search
 At upper right of most pages

Search Menu
 Object-specific searches
 Advanced search
 Ontologies search
 Google search
 BLAST search
 Search of full-text articles (EcoCyc only)

Database Selector
SRI International
Bioinformatics
 Click
on word “change” under Search menu or
under Quick Search button
 In
resulting selector, choose a PGDB
 Start typing a word in organism name
 Click on letter to navigate to organisms starting with that
letter
 Click a frequently used PGDB
 All
subsequent searches will apply to that
database
Quick Search




SRI International
Bioinformatics
Enter a search string in quick search box
Gene Search button searches gene names and synonyms
Quick Search button searches names and synonyms of
 Genes
 Proteins
 RNAs
 GO terms
 Compounds
 Reactions
 Pathways
 Transcription Units
Result page shows all matching objects, organized by
object type
Object Specific Searches
SRI International
Bioinformatics
 Allow
you to create detailed searches against
single types of objects
 Specify
multiple constraints on the object you
want to find
 Click
on triangles at the left to expand or hide
filters
 Note
that if a filter is hidden it will not be used in a
search
SRI International
Bioinformatics
BioCyc Web Site: Object Page Types

Genes + Gene Products
 Enzymes, transporters, transcription factors, others
 Extensive comments and citations
 Monomers and multimers are represented, and in different chemical
states
Reactions
Pathways
Compounds

Searches are organized around these page types



Textpresso Search
 EcoCyc
SRI International
Bioinformatics
only
 Searches
full text of a large corpus of articles
(2010: 24,000 articles)
 Keyword
 Scope
and/or ontology-based searches
is sentence by default
 Results
presented at bottom of page
Textpresso Search
 Keyword
search examples:
 tryptophan yanofsky -- keyword and
 tryptophan,yanofsky -- keyword or
 attenuation –tryptophan – exclude tryptophan
 “excess tryptophan” -- phrase
 Ontology
search examples:
SRI International
Bioinformatics
Additional Searches
SRI International
Bioinformatics
 Advanced
search allows user to formulate
detailed multi-object searches
 Ontology
searches allow the user to drill down
through a classification system to find
information of interest
 Google
search performs search across all web
pages within this site for words of interest
 BLAST
search performs sequence search against
a single specified genome
Web Account System
 Page
formatting preferences
 Omics
viewer preferences
 Comparative
 Receive
analysis preferences
email updates on new releases
SRI International
Bioinformatics
Overview of Object Displays
SRI International
Bioinformatics
Shared Display Characteristics
 Gene-Reaction
schematic
 Citations
and comments
 Database
Links
 Classes
SRI International
Bioinformatics
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
SRI International
Bioinformatics
Citations and Comments
 Citations
 Click
in mnemonic form
on citation – go to citations at bottom of
page
 Click
there, go to PubMed ref, if available
Database Links
 Unification
SRI International
Bioinformatics
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
Class Hierarchies
SRI International
Bioinformatics
 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
Menu Categories
 Pathway
 Reaction
 Protein
 (RNA)
 Gene
 Compound
SRI International
Bioinformatics
SRI International
Bioinformatics
Pathway Mode Commands
 Search
by pathway name
 Search
by substring
 Search
by class
 Search
by substrates (can pick role in pathway)
SRI International
Bioinformatics
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
SRI International
Bioinformatics
Reaction Mode Commands
 Search
by reaction name
 Search
by E.C. #
 Search
by class (another E.C. interface)
 Search
by pathway
 Search
by substrates
SRI International
Bioinformatics
What’s in a reaction frame?
 Search
by EC for 2.6.1.11 (pick one)
 Picture
of reaction with clickable compounds
 Pathways
 Place
the reaction is involved in
in class hierarchy
 Enzymes
carrying out reaction (note schematic)
SRI International
Bioinformatics
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
SRI International
Bioinformatics
What’s in a protein frame?
 Sample
frame (ArgD)
 Synonyms,
general features, comments
 Unification
links, gene-reaction schematic
 GO
terms
reaction frames – how this protein
carries out that reaction (bridging the two)
 Enzymatic
 Evidence
codes
Gene Mode Commands
SRI International
Bioinformatics
 Search
by gene name (can also put in TU IDs)
 Search
by substring
 Get
gene by class
 Basically
the same for RNAs
SRI International
Bioinformatics
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
What’s in a TU frame?
 Sample
 Genes
frame (argCBH)
in context, with TFs
 Promoter
 TF
SRI International
Bioinformatics
with start site and citations
binding sites, with citations
 Regulatory
interactions (ilvL attenuator in TU524)
SRI International
Bioinformatics
Compound Mode Commands
 Search
compound by name
 Search
compound by substring
 Search
by SMILES (structure)
 Search
by class
 Advanced
search
The SMILES Language
 Simplified
SRI International
Bioinformatics
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
SRI International
Bioinformatics
What’s in a compound frame?
 Sample
(N-acetylglutamyl-phosphate)
 Synonyms,
 Structure
 SMILES
empirical formula, MW, links
(you can add these in editors)
code
 Pathways
and reactions involving this compound
SRI International
Bioinformatics
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
User Preferences
 Color
 Layout
 Compound
window
 Reaction window
 Pathway window
 History/Answer list
 Reverting and saving user preferences
SRI International
Bioinformatics
Lab Exercises – Desktop
Version
Lab Exercises
 Set
SRI International
Bioinformatics
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
Desktop Lab Exercises
 Retrieve
SRI International
Bioinformatics
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
Desktop Lab Exercises
 Retrieve
SRI International
Bioinformatics
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
Desktop Lab Exercises
 Retrieve
SRI International
Bioinformatics
all chaperone genes
 Retrieve gene aroA
 Find the glutamine biosynthesis pathway by
issuing each of the three types of queries in
Pathway mode.
Desktop Lab Exercises
 Clone
SRI International
Bioinformatics
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
Web Version Lab Exercises
Web Lab Exercises
 In
SRI International
Bioinformatics
EcoCyc:
 Retrieve
gene aroA
 Retrieve all kinases
 Retrieve all chaperone genes using two different
approaches
 Retrieve all membrane proteins that cite an article
by Gross
 Retrieve all genes whose product interacts with
ppGpp as a regulator or cofactor
Web Lab Exercises
 In
SRI International
Bioinformatics
MetaCyc:
 Retrieve
reaction with EC# 5.3.1.9
 Retrieve compounds adenine and uracil using
ontology search
 Retrieve all reactions involving glutamate as a
substrate
 Find genes coding for enzymes involved in the
degradation of short-chain fatty acids
 Find all pathways involved in degradation of
arginine