Gene Ontology Term Analysis

Revision as of 18:09, 11 November 2009 by Smith (talk | contribs) (References)

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Overview

The Gene Ontology project describes genes (gene products) using terms from three structured vocabularies: biological process, cellular component and molecular function.

A number of analysis methods in geWorkbench a list of interesting genes, for example, those differentially expressed (t-test), or those which show similarities in expression (Hierarchical Clustering, SOM, ARACNe). The Gene Ontology Enrichment component, also referred to as the "GO Terms" component, allows the genes in such a "changed-gene" list to be characterized using their assignments to various categories in the Gene Ontology. It asks, for this list of genes, are any particular GO categories represented at a level higher than expected by chance (enriched), as determined by comparison with their frequency of occurrence in the reference gene list?


The Gene Ontology (GO Terms) analysis component in geWorkbench is built around the Ontologizer 2.0 software product from Peter Robinson's group at the Charite Medical Institute in Berlin. It provides several methods for enrichment analysis, including Term-for-Term, Parent-Child, and Topology. More information about these methods can be found at the Ontologizer website at http://compbio.charite.de/index.php/ontologizer2.html.


This tutorial is currently being developed and will be complete on November 11, 2009.

Analysis Component GUI

Parameters

Selection

T GO Terms Analysis Parameters Selection.png

Reference Gene List

The first pulldown allows one to choose from the following sources for the reference gene list:

  • All Genes - uses all markers in the current microarray dataset.
  • From Set - if chosen, the second pull-down shows the available sets defined in the Markers component.
  • From File - if chosen, the "Load" button becomes active.

Load - If From File is chosen, the user can load a comma-separated list of markers to use as the reference set.

Text field - displays the contents of the currently loaded reference gene list, regardless of source.

Changed Gene List

The first pull-down allows one to choose from the following sources for the changed-gene list:

  • From Set - if chosen, the second pull-down shows the available sets defined in the Markers component.
  • From File - if chosen, the "Load" button becomes active.
  • From Result Node - if chosen, the second pull-down shows a list of available differential expression (t-test, ANOVA) result nodes from the Project Folders component.

Load - If From File is chosen, the user can load a comma-separated list of markers to use as the changed gene list.

Text field - displays the contents of the currently loaded changed-gene list, except if "From Result Node" is chosen.

Ontology Selection

Not currently implemented, this is intended to allow the loading of alternate ontologies besides the three comprising the Gene Ontology.

Ontologizer

T GO Terms Analysis Parameters Ontologizer.png

Annotations

  • Use loaded annotations - If an annotation file was read in when the microarray dataset was loaded, it is displayed here.
  • Use alternate annotation file - A new or alternate annotation file can be read in by selecting this option. Currently only the Affymetrix annotation file format is supported.
  • Alternate annotation text field - if an alternate annotation file is chosen, the file name will be display in this field.
  • Browse - this button brings up a file browser for choosing an annotation file.

Enrichment Method

T GO Terms Analysis Parameters Ontologizer Enrichment.png

Multiple Testing Correction

T GO Terms Analysis Parameters Ontologizer MultipleTestingCorrections.png

  • Benjamini-Hochberg -
  • Benjamini-Yekutieli -
  • Bonferroni -
  • Bonferroni-Holm -
  • None (default) -
  • Westfall-Young-Single-Step -
  • Westfall-Young-Step-Down -

References

  • Alexa A, Rahnenführer J, Lengauer T (2006). Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. Bioinformatics 22(13), pps. 2600-1607 (link to paper)
  • Bauer S, Grossmann S, Vingron M, Robinson PN (2008). Ontologizer 2.0--a multifunctional tool for GO term enrichment analysis and data exploration. Bioinformatics 24(14), pps. 1650-1. (link to paper)
  • Falcon S, Gentleman R. (2007) Using GOstats to test gene lists for GO term association. Bioinformatics 23(2), pps. 257-8. (link to paper)
  • Grossmann S, Bauer S, Robinson PN, Vingron M (2007). Improved detection of overrepresentation of Gene-Ontology annotations with parent child analysis. Bioinformatics 23(22), pps. 3024-31. (link to paper)
  • Robinson PN, Wollstein A, Böhme U, Beattie B. (2004) Ontologizing gene-expression microarray data: characterizing clusters with Gene Ontology. Bioinformatics 20(6), pps. 979-81. (link to paper)