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SRI InternationalBioinformaticsIntroduction
Each overview is a genome-scale diagram of cellular machinery
Cellular Overview Regulatory Overview Genome Overview
Overviews painted with omics data become omics viewers
SRI InternationalBioinformaticsThe Cellular Overview Diagram
Metabolic pathways, transporters, other membrane proteins, periplasmic proteins
Generated automatically by Pathway Tools
Can be a static display or a dataset viewing tool
Can be printed as a poster
SRI InternationalBioinformaticsOrganization of the Overview
Lines are reactions, nodes are biochemical species (compounds, proteins)
There’s a legend explaining symbols usedIncludes metabolic and transport reactionsPathways grouped functionally
Anabolism on the left, catabolism on the right, energy in the middle
Gray backgrounds indicate more specific functional groups Non-pathway reactions on far right
Generally, pathways flow downward
SRI InternationalBioinformaticsPhysical Location in the
Overview
Non-cytoplasmic proteins with known locations shown
In E. coli, that means periplasmic, cell and outer membrane This includes proteins with no associated reaction
Cytoplasmic proteins with enzymatic activities shown
Non-enzymatic cytoplasmic proteins left off to avoid clutterCompare the gram-positive B. anthracis
Note pathway holes visualized as gray linesOverview>Show/Hide Transport Links
SRI InternationalBioinformaticsMousing Over in the Overview
Mousing over a gray backing tells you the pathway class
Mousing over a node gives compound name and pathway
Mousing over a line gives similar informationCan click through from anything to the PGDBCan right-click to:
Zoom Pop up pathways Indicate pathway connections (clear in overview menu) More
SRI InternationalBioinformaticsHighlighting in the Overview
Overview>Highlight>many options Pathway by class (biosynthesis > all > select all) Reactions > All without EC numbers (note second color)
Note all reaction options (many!) Reactions > By modulation
Can clear highlighting at any timeCan save highlighting to file for later useCan do Genes and Compounds as wellCan pull information from a file, or from answer
list
SRI InternationalBioinformaticsHighlighting to Compare
Organisms
Look at shared or nonshared reactionsExample – E. coli reactions shared with humansExample – switch to a second organism
Reactions not shared with (human and coli) Set from Any to All One way to think about drug targeting, e.g.
Quick note – cross-species comparison from pathways
Go to this from individual pathway pages Compares presence of pathway in question, and reactions of
that pathway
SRI InternationalBioinformaticsThe Genome Overview Diagram
Shows genes schematically, not to scale (unlike Genome Browser)
Shows transcription units and direction of transcription
Shows protein versus RNA coding status
Mouse over for gene name, product, pathway participation, and intergenic spacing
SRI InternationalBioinformaticsThe Regulatory Overview
Diagram
Displays the regulatory network for your organism
At the moment, regulatory relationships are only curated
Rings show regulatory status Inner – regulators only Middle – regulators that are also regulated Outer – regulated only
SRI InternationalBioinformaticsExposing Regulatory
Relationships
Pick a gene and right-click on it – will be presented with options
Can show direct and indirect regulators and regulatees
Display options available in the menu
Can show just the interacting part of the network
SRI InternationalBioinformaticsThe Omics Viewers
Intuitive, visual displays of large data sets
Visualize any data that attaches numbers to genes, proteins or compounds
Proteomics, metabolomics, genomics
Accepts tab-delimited and SAM datasets
SRI InternationalBioinformaticsUsing the Omics Viewers
Overview>Omics Viewer>Text File / SAM OutputSingle-time-point experiment
Choose display Relative/absolute data What kind of data? Which column is the data in? (Object IDs must be in zero)
Color schemes Default (not standard between different datasets) Others (see next slide)
SRI InternationalBioinformaticsOmics Viewer Output
Data report Total data rows Data rows not shown Data rows with invalid data Color key
Display options Set maximum cutoff for default color scheme (e.g. 0.3) Set manual color cutoffs (e.g. 0.3, 0.6, 0.9) Both options let you compare different experiments
SRI InternationalBioinformaticsViewing Multiple Data Sets
View as an AnimationTypically a time course, but does not have to beNeed to tell Pathway Tools which columns to useSame output color / cutoff selections as single
experimentIf you use automatic color scale, it’s set to the
maximum shift in the experiment Thus, all time points / data sets comparable A good way to standardize across experiments
Can move between experiments/time points manually
Can save as HTML
SRI InternationalBioinformaticsObject Groups
Define and save groups of genes, metabolites, pathways, etc
Paint groups onto overviewsCombine groupsTransform groupsPerform enrichment analysis
Desktop mode only
SRI InternationalBioinformaticsGroup Creation
Groups can contain one or more object types
Add current object to groupRight-click on object
Add from answer list
Add from file
Type in names of objects
SRI InternationalBioinformaticsCombine Groups
UnionIntersectionDifferenceExclusive-Or
Can be used to combine query results
SRI InternationalBioinformaticsTransform Groups
Genes -> All pathways containing those genesGenes -> All TFs that regulate those genes
Compounds -> All pathways containing them
SRI InternationalBioinformaticsTransformation Examples
EcoCyc: Create an empty group Add “superpathway of chorismate” Transform to genes of pathway Transform to regulators of gene
SRI InternationalBioinformaticsEnrichment Analysis
Is some group statistically enriched for members of a set within a PGDB?
Examples: Is a group of genes enriched for genes in one or more
metabolic pathways? Is a group of metabolites enriched for membership in one or
more metabolic pathways?