The Pathway/Genome Navigator

SRI InternationalBioinformatics

Overview

Data page types

General query strategies

Web queries

Desktop Pathway Tools

User preferences

Lab exercises

SRI InternationalBioinformaticsPathway/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 http://biocyc.org/desktop-vs-web-mode.shtml

SRI InternationalBioinformaticsData 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

SRI InternationalBioinformaticsDirect 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

SRI InternationalBioinformaticsIndirect Queries

Find an object by searching for an object that is probably related to it

Then navigate to the object you seek

SRI InternationalBioinformaticsComplex Queries

Define multi-criteria searches

System returns all objects that meet those criteria

SRI InternationalBioinformaticsBioCyc 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 email updates on new releases

SRI InternationalBioinformaticsWeb Searches

Multiple searches available for finding information in different ways

Quick search (simplest search)

Object-specific searches

Ontology-based searches

Advanced search http://biocyc.org/query.html

Searches of full-text literature articles

SRI InternationalBioinformaticsSelect Current Organism

Click on “change” Under Quick Search button Bottom of Search menu Bottom of Tools menu

Select by typing or clicking

SRI InternationalBioinformaticsOrganism Pages

Tools -> Reports -> Summary statistics PGDB authors, statistics

SRI InternationalBioinformaticsSample Web Searches for

EcoCyc

Quick Search: xylQuick Search: trpa type:geneQuick Search: b1200

Search -> Genes/Proteins/RNAs 40 < MW < 50 and 5.5 < pI < 6.0 3000000 < Map-Position < 3500000 and Has Gene Ontology term “locomotion” (under Biological Process)

SRI InternationalBioinformaticsSample Web Searches for

HumanCyc

Quick Search: dopamineQuick Search: dopamine type:compoundQuick Search: b1200

Search -> Genes/Proteins/RNAs Enzymes using Mg2+ as a cofactor

Search -> Compounds 300 <= MW <= 320 and containing N

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

Relationship links: PDB-Homolog-P34554

Desktop Mode

SRI InternationalBioinformaticsDesktop Mode

Linux/PC, Windows/PC, Macintosh

SRI InternationalBioinformatics

Desktop Window 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)

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

SRI InternationalBioinformaticsQueries with Multiple Answers

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

Answer List Next Answer

SRI InternationalBioinformaticsOrganism Pages

All Organisms Page – Starting Page Organism grouping Summary of organisms

Single organism page PGDB authors, statistics

SRI InternationalBioinformaticsSelect Current Organism

From All Organisms Page

Through organism selector

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 Page?

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 Transcription Unit

Page?

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 Page?

Sample (N-acetylglutamyl-phosphate)

Synonyms, empirical formula, MW, links

Structure

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 InternationalBioinformaticsHistory List

Backward history

Forward history

Select from history

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