Lecture 16

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Fast Sequence Database Searches (BLAST)

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(*) Computing E-values is possible for HSPs since the statistcs of gap-less alignments are analytically tractable. Similar conclusions in general cannot be drawn from gapped alignments. Note the E-values are not a statement about the retrieved hit, but a statement about an expected distribution of scores. Or, to rephrase this, a poor e-value does not mean that your hit is not a homologue, but it means that at that score an irrelevant sequence has a a high chance of scoring well due to chance similarities.

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(*) Note that restricting by organism is not a restriction on the search, but a restriction on the list of results that are being reported. The search takes just as long. Many databases of model-organism genome projects offer BLAST searches on their specific data. These may be faster.

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(*) How many? That depends. Unknown genes (or "ORFans") may comprise a significant (albeit diminishing) fraction of genomes. See Siew&Fischer(2003) and the ORFan database