Overviews and Omics Viewers
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Overviews and Omics Viewers
SRI InternationalBioinformaticsIntroduction
Each overview is a genome-scale diagram of a different aspect of the 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
Desktop vs Web version: Desktop has more commands currently Web version can be faster to zoom
SRI InternationalBioinformaticsOrganization of the
Cellular 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 gray background identifies pathway class
Mousing over a node gives compound name and pathway
Mousing over a line gives reaction informationCan click through from anything to the PGDB
SRI InternationalBioinformaticsZooming and Panning
Web mode: Hold mouse and drag to pan Click ladder at upper left, or double-click to zoom
Desktop: right-click to Zoom Pop up pathways Indicate pathway connections (clear in overview menu) More
SRI InternationalBioinformaticsHighlighting in the Overview
Desktop Mode
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 in the Overview
Web Mode
Cellular Overview>Highlight>many optionsClear/enable individual highlights using switching
panel at upper rightCan save highlighting to file for later useMultiple highlight
Highlight/Omics View Based on Names and Frame IDs
Generate URL that will re-create current highlighting pattern
Cellular Overview>Generate Bookmark for Current …
SRI InternationalBioinformatics
Highlighting to Compare OrganismsDesktop ModeLook 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 InternationalBioinformaticsGenome Overview
To enter (desktop mode): Overviews > Show Genome Overview Genome Browser: Click level 4 (Genome)
To enter (web mode): Tools > Genome Overview Genome Browser: Click level 4 (Genome)
Mouse over genes for more informationDesktop: Substring search available
SRI InternationalBioinformaticsRegulatory Overview
Displays the regulatory network for an organism
At the moment, regulatory relationships must curated or loaded from an external database
Rings show regulatory status Inner – regulators only Middle – regulators that are also regulated Outer – regulated only
Desktop: Overviews > Show Regulatory OverviewWeb: Tools > Regulatory Overview
SRI InternationalBioinformaticsExploring Regulatory
Relationships
Pick a gene and right-click on it – will be presented with options
Highlight genes by GO terms or substring
Can show direct and indirect regulators and regulatees
Display options available in the menu Change layout Display highlighted genes only Zoom and pan
SRI InternationalBioinformaticsAnalysis of Omics Datasets
Omics Viewers Cellular Overview Regulatory Overview Genome Overview
Genome Browser tracks
Groups facility Define groups of differentially regulated genes Perform enrichment analysis Transform to operons Transform to significantly expressed pathways
SRI InternationalBioinformaticsThe Omics Viewers
Intuitive, visual displays of large data sets using the three overviews
Visualize any data that attaches numbers to genes, proteins or compounds
Proteomics, metabolomics, genomics
Accept tab-delimited and SAM (desktop only) datasets
Some differences between desktop and web versions
Omics pop-ups are desktop only
SRI InternationalBioinformaticsUsing the Omics Viewers
Entry Desktop: Overview>Omics Viewer>Text File / SAM Output Web: Cellular Overview > Highlight Experimental Data
Single-time-point experiment Choose which omics viewers to use
Data file Object IDs must be in column zero What object IDs to use? Which column is the data in? Labels can be specified in the data file in first non-comment
line: $Label1 Label2 Label3
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 InternationalBioinformaticsOmics Viewer Options
Relative vs absolute Absolute: Concentrations or molecule counts. Negative
values are ignored. Relative: Assumes values are centered
0-centered vs 1-centered scale 0-centered = log scale with positive and negative values 1-centered = linear scale, centered on 1, log transform
SRI InternationalBioinformaticsOmics Viewer Color Schemes
Full color spectrum from data Data from one file mapped to full color spectrum Different experiments will receive different color assignments
Full color spectrum with max cutoff User specifies cutoff Useful for comparing datasets
Three color display with threshold Three color bins: x < 1/T , 1/T < x < T, x > T
User-defined bins with computer colorsUser-defined bins with user colors
SRI InternationalBioinformaticsViewing Multiple Data Sets
Compare multiple data points using 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 InternationalBioinformaticsOmics Pop-Ups
Desktop only for now; web versions to come
SRI InternationalBioinformatics
Omics Data Graphing on Cellular Overview
SRI InternationalBioinformatics
SRI InternationalBioinformaticsUsing Groups for Omics
Data Analysis
Define group from omics data file
Enrichment analysis
Groups Transform Group Pathways of Gene Significant Pathways of Gene Genes in Same Operon Regulators of Gene Enrichment Analysis
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