The Pathway/Genome Navigator

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

SRI InternationalBioinformatics

Pathway/Genome Navigator – topics

Getting started with the NavigatorOrganism pagesQueries in generalObject displays and queriesMiscellaneous commandsUser preferencesLab exercises

SRI InternationalBioinformaticsIntroduction

Navigator runs both on the desktop and on the web

The desktop version generally has more capabilities

SRI InternationalBioinformatics

Desktop Layout

One Large Window

Several Panes: Display pane Command menu LISP listener

SRI InternationalBioinformaticsMenus

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

SRI InternationalBioinformaticsUsing 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 won’t use it)

Mouse documentation line (shows what you’re over, what you can do)

SRI InternationalBioinformaticsOrganism 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 InternationalBioinformaticsQueries with multiple answers

Results in form of a menu to: select one some all

Answer List Next Answer

SRI InternationalBioinformaticsIndirect Queries

Related objects

Objects are clickable

Objects are color-coded by type

SRI InternationalBioinformaticsHistory List

Backward history

Forward history

Select from history

SRI InternationalBioinformaticsComplex 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

SRI InternationalBioinformaticsShared Display Characteristics

Gene-Reaction schematic

Citations and comments

Database Links

Classes

SRI InternationalBioinformaticsGene-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, rxnsLinks proteins with shared reactions

ArgDLinks members of protein complexes

Pol III – extreme example

SRI InternationalBioinformaticsCitations and Comments

Citations in mnemonic form

Click on citation – go to citations at bottom of page

Click there, go to PubMed ref, if available

SRI InternationalBioinformaticsDatabase 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

SRI InternationalBioinformaticsClass 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

SRI InternationalBioinformaticsMenu Categories

PathwayReactionProtein(RNA)GeneCompound

SRI InternationalBioinformaticsPathway Mode Commands

Search by pathway name

Search by substring

Search by class

Search by substrates (can pick role in pathway)

SRI InternationalBioinformaticsWhat’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 InternationalBioinformaticsReaction Mode Commands

Search by reaction name

Search by E.C. #

Search by class (another E.C. interface)

Search by pathway

Search by substrates

SRI InternationalBioinformaticsWhat’s 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)

SRI InternationalBioinformaticsProtein Mode Commands

Search by protein nameSearch by substringSearch by pathwaySearch by organism (MetaCyc)Search by UniProt AccSearch by GO termSearch by MultiFun termSearch by Weight, pISearch by modulation of activity

SRI InternationalBioinformaticsWhat’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

SRI InternationalBioinformaticsGene Mode Commands

Search by gene name (can also put in TU IDs)

Search by substring

Get gene by class

Basically the same for RNAs

SRI InternationalBioinformaticsWhat’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

SRI InternationalBioinformaticsWhat’s 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)

SRI InternationalBioinformaticsCompound Mode Commands

Search compound by name

Search compound by substring

Search by SMILES (structure)

Search by class

Advanced search

SRI InternationalBioinformaticsThe SMILES Language

Simplified Molecular Input Line Entry SystemFormal language for describing chemical

structuresUsed within the Pathway Tools in a substructure

searchCase is significant (lowercase for aromatic rings)Examples:

formate C(=O)Omalate OC(=O)CC(O)C(O)=O

For more information, see the Help facility

SRI InternationalBioinformaticsWhat’s 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

SRI InternationalBioinformaticsMiscellaneous Commands

History commandsAnswer-List commandsClone window commandFix window and unfix window commandsOther commands:

Print to file (makes a postscript) Help Preferences Exit

SRI InternationalBioinformaticsUser Preferences

ColorLayoutCompound windowReaction windowPathway windowHistory/Answer listReverting and saving user preferences

SRI InternationalBioinformaticsLab Exercises

Set up personal preferences for:

Color

Layout (set number of windows to 2)Save new preferencesPlay with settings for Compound, Reaction,

Pathway, and Overview windows.Choose settings for History/Answer List

preferences

SRI InternationalBioinformaticsLab Exercises

Retrieve compounds containing a formate groupRetrieve compounds adenine and uracil using

class query Retrieve reaction with EC# 5.3.1.9Retrieve all reactions in the class

sulfurtransferasesRetrieve all reactions involved in proline

biosynthesisRetrieve all reactions where glutamate appears on

left sidegenes coding for enzymes involved in the

degradation of short-chain fatty acids

SRI InternationalBioinformaticsLab Exercises

Retrieve all enzymes involved in purine biosynthesis

Retrieve all kinasesDisplay region spanning from 10 % - 20 % of E.

coli chromosome Display chromosomal region around gene aroADisplay a map showing all chaperone genes

SRI InternationalBioinformaticsLab Exercises

Retrieve all chaperone genesRetrieve gene aroAFind the glutamine biosynthesis pathway by

issuing each of the three types of queries in Pathway mode.

SRI InternationalBioinformaticsLab Exercises

Clone windowNavigate in the cloned windowSet preferences so Navigator displays 2 windowsNavigate by clicking on live objectsFix WindowNavigate in unfixed windowFix second window and then click on live object