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, but each has unique features

Desktop Mode -- Introduction

SRI InternationalBioinformatics

Desktop Layout

One Large Window

Several Panes: Display pane Command menu LISP listener

SRI InternationalBioinformaticsDesktop 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

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 InternationalBioinformaticsWriting 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 Siteand Other

Pathway Tools Based Web Sites

SRI InternationalBioinformaticsBioCyc Searches

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)

SRI InternationalBioinformaticsDatabase Selector

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

SRI InternationalBioinformaticsQuick Search

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

SRI InternationalBioinformaticsObject Specific Searches

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 InternationalBioinformaticsBioCyc 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

SRI InternationalBioinformaticsTextpresso Search

EcoCyc only

Searches full text of a large corpus of articles (2010: 24,000 articles)

Keyword and/or ontology-based searches

Scope is sentence by default

Results presented at bottom of page

SRI InternationalBioinformaticsTextpresso Search

Keyword search examples: tryptophan yanofsky -- keyword and tryptophan,yanofsky -- keyword or attenuation –tryptophan – exclude tryptophan “excess tryptophan” -- phrase

Ontology search examples:

SRI InternationalBioinformaticsAdditional Searches

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

SRI InternationalBioinformaticsWeb Account System

Page formatting preferences

Omics viewer preferences

Comparative analysis preferences

Receive email updates on new releases

Overview of Object Displays

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

Lab Exercises – Desktop Version

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 InternationalBioinformaticsDesktop Lab 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 InternationalBioinformaticsDesktop Lab 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 InternationalBioinformaticsDesktop Lab Exercises

Retrieve all chaperone genesRetrieve gene aroAFind the glutamine biosynthesis pathway by

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

SRI InternationalBioinformaticsDesktop Lab 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

Web Version Lab Exercises

SRI InternationalBioinformaticsWeb Lab Exercises

In EcoCyc:

Retrieve gene aroARetrieve all kinasesRetrieve all chaperone genes using two different

approachesRetrieve all membrane proteins that cite an article

by GrossRetrieve all genes whose product interacts with

ppGpp as a regulator or cofactor

SRI InternationalBioinformaticsWeb Lab Exercises

In MetaCyc:

Retrieve reaction with EC# 5.3.1.9Retrieve compounds adenine and uracil using

ontology search Retrieve all reactions involving glutamate as a

substrateFind genes coding for enzymes involved in the

degradation of short-chain fatty acidsFind all pathways involved in degradation of

arginine