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Feb21_Alignment - Integrative Biology 200A"PRINCIPLES OF...

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1 Integrative Biology 200A “PRINCIPLES OF PHYLOGENETICS” Spring 2008 University of California, Berkeley Will- 21 Feb 2008 Alignment Two or more sequences (bases, amino acids, proteins, etc.) are matched in a pairwise alignment either globally (two sequences matched over their whole length) or locally (some subset of the sequences matched while other regions are not expected to match). Sequence similarity can simply be a mathematical distance between two. Establishing an initial estimate of homology (basically similarity) is essential. Unaligned sequence data has no a priori base homology. As a consequence, the fixed alignment, achieved by one method or another, is treated as prior, or background knowledge. Recall the hierarchy of characters and state and that only the states are really tested in the analyses. The outcome phylogenetic analyses are often strongly influenced by the alignment. BLAST ( Altschul, SF, W Gish, W Miller, EW Myers, and DJ Lipman. Basic local alignment search tool. J Mol Biol 215(3):403-10, 1990) . For example, a gene is newly identified and function understood in Drosophila , a researcher can BLAST the database of the human genome to look for similar gene sequences. Very basic description of BLAST 1. Uses short segments (“words”) of sequence to find other sequences that contain the same set. 2. Does “ungapped” alignment extending from the matched subsequence regions to find high-scoring matches 3. Does a rapid gapped alignment to select and rank close matches Practical issues : For two sequences, i.e. pairwise alignment, of length n, if no gaps are allowed then there is one or few optimal alignment(s). If gaps are allowed, i.e. there is sequence length variation, then... (2n)!/(n!) 2 e.g. n=50 then 10 29 alignments. Enumeration is not an option! We need heuristic searches based on Optimality and scoring. Two problems- how to find alignments and how to choose. Alignment really attempts to balance the amount of indels with the amount of base substitution, normally based on some cost differential. Of course it is possible to account for all differences by inserting enough gaps (trivial alignment). In the simplest model this is the “Edit distance” or the minimal number of events required to transform one sequence into another using some scheme of insertions, deletions and substitutions.
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  • Spring '08
  • Alignment, Sequence alignment, Basic Local Alignment, Multiple sequence alignment, global alignment, rapid gapped alignment

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Feb21_Alignment - Integrative Biology 200A"PRINCIPLES OF...

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