Using Gene Ontology

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Using Gene Ontology
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Assigning (or Hypothesizing About) Biological
Meaning to Clusters

• What do you want to be able to to?
• Identify over-represented functional categories
  in the clusters (i.e., cluster contains may more
  genes known to be involved in a specific
  biological process than would be expected by
  chance)
• Why do you want to be able to do this?
• If you find a gene of unknown function in a
  cluster of genes in which a known function is
  overrepresented, your gene of unknown function
  may have the same or a related function!
• Requirements for systematic analysis
• Standard assignment of genes into functional
  categories
• Gene Ontology or GO project at NCBI
• Controlled vocabulary for describing biological
  processes (protein biosynthesis\translation,
  apoptosis\programmed cell death)

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Gene Ontology (GO) projecthttp//www.geneontology
.org/

• Purpose
• 1) Establish a unified framework for
  organism-independent gene annotation
• 2) Define controlled terms (ontologies) for
  description of gene products from 3 aspects
• Biological process (DNA repair, mitosis)
• Molecular function (protein serine/threonine
  kinase activity, transcription factor activity)
• Cellular component (nucleus, ribosome)
• Characteristics
• 1) A gene can have multiple associations in each
  ontology
• 2) GO terms are organized in hierarchical
  structures called directed acyclic graphs (DAGs)
• - The most general classifications are at top
  levels of the graph
• - More specialized classifications at lower
  levels

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(No Transcript)
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Example Cluster 3, 95 genes
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Identifying enriched GO categories in clusters

• In the previous example
• Total number of chips genes with annotation
  5000
• Remember, some genes may be of unknown function
  and not be annotated.
• Total number of chips genes associated with
  metabolism GO category 3,600 (72)
• Number of annotated genes in cluster 3 73
• Number of metabolic genes in cluster 3 50 (68)
• Is it reasonable to assume that genes in Cluster
  3 are enriched for metabolic function?
• Statistical tests are essential to determine
  whether enrichment of a certain class of proteins
  is significant

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Online Databases that annotate genes by GO

• Human
• Entrez http//www.ncbi.nih.gov/entrez/query.fcgi?d
  bgene
• GOA http//www.ebi.ac.uk/GOA/
• Mouse Mouse Genome Informatics (MGI)
• http//www.informatics.jax.org/
• Rat Rat Genome Database
• http//rgd.mcw.edu/
• Fly FlyBase
• http//flybase.bio.indiana.edu/
• Arabidopsis TAIR
• http//www.arabidopsis.org/
• Yeast Sacchromaces Genome Database
• http//www.yeastgenome.org/
• Affymetrix chips Netaffx
• http//www.affymetrix.com