msa-Lecture3

msa-Lecture3 - Lecture 3: Multiple Sequence Alignment Eric...

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Lecture 3: Multiple Sequence Alignment Eric C. Rouchka, D.Sc. eric.rouchka@uofl.edu http://kbrin.a-bldg.louisville.edu/~rouchka/CECS694/
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Amino Acid Sequence Alignment No exact match/mismatch scores Match state score calculated by table lookup Lookup table is mutation matrix
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PAM250 Lookup
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Affine Gap Penalties Gap Open Gap Extension Maximum score matrix determined by maximum of three matrices: Insertion matrix (gap in sequence A) Deletion matrix (gap in sequence B)
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Dynamic Programming with Affine Gap M i,j = MAX{ M i-1, j-1 + s(x i , y i ), I i-1, j-1 + s(x i , y i ), D i-1, j-1 + s(x i , y i ) } I i,j = MAX{ M i-1, j – g, // Opening new gap, g = gap open penalty; I i-1, j – r} // Extending existing gap, r = gap extend penalty D i,j = MAX{M i,j-1 – g, // Opening new gap; D i,j-1 – r} // Extending existing gap V i,j = MAX {M i,j , I i,j , D i,j }
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Programming Project #1 Don’t worry about affine gaps – will become part of programming project 2 Make sure you can align DNA and amino acid sequence
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Multiple Sequence Alignment Similar genes conserved across organisms Same or similar function
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Multiple Sequence Alignment Simultaneous alignment of similar genes yields: regions subject to mutation regions of conservation mutations or rearrangements causing change in conformation or function
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Multiple Sequence Alignment New sequence can be aligned with known sequences Yields insight into structure and function Multiple alignment can detect important features or motifs
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Multiple Sequence Alignment GOAL: Take 3 or more sequences, align so greatest number of characters are in the same column Difficulty: introduction of multiple sequences increases combination of matches, mismatches, gaps
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Example Multiple Alignment Example alignment of 8 IG sequences.
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Approaches to Multiple Alignment Dynamic Programming Progressive Alignment Iterative Alignment Statistical Modeling
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Dynamic Programming Approach Dynamic programming with two sequences Relatively easy to code Guaranteed to obtain optimal alignment Can this be extended to multiple sequences?
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Dynamic Programming With 3 Sequences Consider the amino acid sequences VSNS, SNA, AS Put one sequence per axis (x, y, z) Three dimensional structure results
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This note was uploaded on 02/13/2012 for the course CS 91.510 taught by Professor Staff during the Fall '09 term at UMass Lowell.

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msa-Lecture3 - Lecture 3: Multiple Sequence Alignment Eric...

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