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Try to answer the following questions:
  1. What are the component ontologies of the Gene Ontology?
  2. What kind of graph is the Gene Ontology?
    • What properties are specific to such a graph?
  3. Two genes, X and Y, are annotated with molecular function ontology terms, A and B (respectively). Using pseudocode (or plain English that is precise enough to base actual code on), outline how you would find the most specific ontology term T that applies to both X and Y.
  4. Explain the distinction between a gene and a gene ontology term .
    • How much information (in the Shannon sense) is conveyed by a typical gene ontology term annotation?
      • Refer to the following paper in your reply (e.g. Figure 1): Alterovitz G et al.  Ontology engineering.  Nat Biotechnol. 2010 Feb;28(2):128-30. doi: 10.1038/nbt0210-128.
  5. What is the Wikipedia:Hypergeometric_distribution ?
    1. The yeast genome contains approximately 7547 genes (5213 experimentally verified, 2334 predicted). Of these, 463 are annotated with GO:0003677 (DNA binding). A microarray experiment identifies a set of 273 genes that are expressed in response to a particular chemical stimulus, of which 5 are annotated with the same GO term. Compute a p-value for this observation by summing out the tail of a hypergeometric distribution, showing your working.
    2. Suppose that this observation occurs in the context of a search for enriched terms in an ontology that contains a total of 127 terms. What inequality should your p-value satisfy in order to be <1% significant in the context of this search?
  6. What is...
    1. a GO "gene association" set? (or file?)
    2. the transitive closure of a gene association set?
    3. the relationship between transitive closure and syllogism?
  7. Other than the Gene Ontology, describe up to three ontologies in each of these areas:
    1. genomics
    2. clinical medicine
    3. neuroscience
    4. biochemistry

-- IanHolmes - 17 Nov 2010

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