Title: The Pathway/Genome Navigator
1The Pathway/Genome Navigator
2Overview
- Data page types
- General query strategies
- Web queries
- Desktop Pathway Tools
- User preferences
- Lab exercises
3Pathway/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
4Data 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
5Direct 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 dont know an exact name
- Searches that are specific to object type
6Indirect Queries
- Find an object by searching for an object that is
probably related to it - Then navigate to the object you seek
7Complex Queries
- Define multi-criteria searches
- System returns all objects that meet those
criteria
8BioCyc 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
9Web 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
10Select Current Organism
- Click on change
- Under Quick Search button
- Bottom of Search menu
- Bottom of Tools menu
- Select by typing or clicking
11Organism Pages
- Tools -gt Reports -gt Summary statistics
- PGDB authors, statistics
12Sample Web Searches for EcoCyc
- Quick Search xyl
- Quick Search trpa typegene
- Quick Search b1200
- Search -gt Genes/Proteins/RNAs
- 40 lt MW lt 50 and 5.5 lt pI lt 6.0
- 3000000 lt Map-Position lt 3500000 and
- Has Gene Ontology term locomotion
- (under Biological Process)
13Sample Web Searches for HumanCyc
- Quick Search dopamine
- Quick Search dopamine typecompound
- Quick Search b1200
- Search -gt Genes/Proteins/RNAs
- Enzymes using Mg2 as a cofactor
- Search -gt Compounds
- 300 lt MW lt 320 and containing N
14Shared Display Characteristics
- Gene-Reaction schematic
- Citations and comments
- Database Links
- Classes
15Gene-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
16Citations and Comments
- Citations in mnemonic form
- Click on citation go to citations at bottom of
page - Click there, go to PubMed ref, if available
17Database Links
- Unification links (info about the protein
elsewhere) - PDB
- PIR
- RefSeq
- UniProt
- Relationship links
- PDB-Homolog-P34554
18Class 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
19Desktop Mode
20Desktop Mode
- Linux/PC, Windows/PC, Macintosh
21Desktop Window Layout
- One Large Window
- Several Panes
- Display pane
- Command menu
- LISP listener
22Menus
- 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
23Using 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 youre over,
what you can do)
24Queries with Multiple Answers
- Results in form of a menu to
- select one
- some
- all
- Answer List
- Next Answer
25Organism Pages
- All Organisms Page Starting Page
- Organism grouping
- Summary of organisms
- Single organism page
- PGDB authors, statistics
26Select Current Organism
- From All Organisms Page
- Through organism selector
27Pathway Mode Commands
- Search by pathway name
- Search by substring
- Search by class
- Search by substrates (can pick role in pathway)
28Whats 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
29Reaction Mode Commands
- Search by reaction name
- Search by E.C.
- Search by class (another E.C. interface)
- Search by pathway
- Search by substrates
30Whats 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)
31Protein 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
32Whats 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
33Gene Mode Commands
- Search by gene name (can also put in TU IDs)
- Search by substring
- Get gene by class
- Basically the same for RNAs
34Whats 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
35Whats 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)
36Compound Mode Commands
- Search compound by name
- Search compound by substring
- Search by SMILES (structure)
- Search by class
- Advanced search
37The 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
38Whats in a Compound Page?
- Sample (N-acetylglutamyl-phosphate)
- Synonyms, empirical formula, MW, links
- Structure
- SMILES code
- Pathways and reactions involving this compound
39Miscellaneous 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
40History List
- Backward history
- Forward history
- Select from history
41User Preferences
- Color
- Layout
- Compound window
- Reaction window
- Pathway window
- History/Answer list
- Reverting and saving user preferences
42Program-Based Queries
- 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
43Lab 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
44Lab 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
45Lab 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
46Lab 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.
47Lab 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