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    BLOSUM Matrices

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    Raj Kumar Soni
    BLOSUM matrices are substitution matrices derived from blocks of local sequence alignments with varying levels of identity. They provide scoring values for aligning amino acids in protein sequences. BLOSUM62 is commonly used as it is derived from blocks with less than 62% identity. The matrices are constructed by counting amino acid pairs in alignments, normalizing to probabilities, and calculating log-odds scores. They do not assume an evolutionary model like PAM matrices but rather conserved blocks in proteins.

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    BLOSUM Matrices

    Uploaded by

    Raj Kumar Soni
    485 views18 pages
    BLOSUM matrices are substitution matrices derived from blocks of local sequence alignments with varying levels of identity. They provide scoring values for aligning amino acids in protein sequences. BLOSUM62 is commonly used as it is derived from blocks with less than 62% identity. The matrices are constructed by counting amino acid pairs in alignments, normalizing to probabilities, and calculating log-odds scores. They do not assume an evolutionary model like PAM matrices but rather conserved blocks in proteins.

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    BLOSUM matrices are substitution matrices derived from blocks of local sequence alignments with varying levels of identity. They provide scoring values for aligning amino acids in protein sequences. BLOSUM62 is commonly used as it is derived from blocks with less than 62% identity. The matrices are constructed by counting amino acid pairs in alignments, normalizing to probabilities, and calculating log-odds scores. They do not assume an evolutionary model like PAM matrices but rather conserved blocks in proteins.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    485 views18 pages

    BLOSUM Matrices

    Uploaded by

    Raj Kumar Soni
    BLOSUM matrices are substitution matrices derived from blocks of local sequence alignments with varying levels of identity. They provide scoring values for aligning amino acids in protein sequences. BLOSUM62 is commonly used as it is derived from blocks with less than 62% identity. The matrices are constructed by counting amino acid pairs in alignments, normalizing to probabilities, and calculating log-odds scores. They do not assume an evolutionary model like PAM matrices but rather conserved blocks in proteins.

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    Alignment IV

    BLOSUM Matrices
    BLOSUM matrices

    • Blocks Substitution Matrix. Scores


    for each position are obtained
    frequencies of substitutions in blocks
    of local alignments of protein
    sequences [Henikoff & Henikoff92].
    • For example BLOSUM62 is derived
    from sequence alignments with no
    more than 62% identity.
    2
    BLOSUM Scoring Matrices

    • BLOck SUbstitution Matrix


    • Based on comparisons of blocks of sequences
    derived from the Blocks database
    • The Blocks database contains multiply aligned
    ungapped segments corresponding to the most
    highly conserved regions of proteins (local
    alignment versus global alignment)
    • BLOSUM matrices are derived from blocks whose
    alignment corresponds to the BLOSUM-,matrix
    number

    3
    Conserved blocks in alignments

    AABCDA...BBCDA
    DABCDA.A.BBCBB
    BBBCDABA.BCCAA
    AAACDAC.DCBCDB
    CCBADAB.DBBDCC
    AAACAA...BBCCC

    4
    Constructing BLOSUM r
    • To avoid bias in favor of a certain protein, first
    eliminate sequences that are more than r%
    identical
    • The elimination is done by either
    – removing sequences from the block, or
    – finding a cluster of similar sequences and replacing it by
    a new sequence that represents the cluster.
    • BLOSUM r is the matrix built from blocks with no
    more the r% of similarity
    – E.g., BLOSUM62 is the matrix built using sequences with
    no more than 62% similarity.
    – Note: BLOSUM 62 is the default matrix for protein
    BLAST

    5
    Collecting substitution statistics

    1. Count amino acids pairs in each


    column; e.g., A
    – 6 AA pairs, 4 AB pairs, 4 AC, 1 BC, 0 BB, A
    0 CC.
    – Total = 6+4+4+1=15
    B
    A
    2. Normalize results to obtain
    probabilities (pX’s and qXY’s) C
    A
    3. Compute log-odds score matrix from
    probabilities:
    s(X,Y) = log (qXY / (pX py))
    6
    Computing probabilities

    From http://www.csit.fsu.edu/~swofford/bioinformatics_spring05/lectures/lecture03-blosum.pdf
    7
    Computing probabilities

    8
    Computing probabilities

    9
    Example

    From http://www.csit.fsu.edu/~swofford/bioinformatics_spring05/lectures/lecture03-blosum.pdf
    10
    Example

    11
    Example

    12
    Example

    13
    Comparison
    • PAM is based on an evolutionary model
    using phylogenetic trees
    • BLOSUM assumes no evolutionary model,
    but rather conserved “blocks” of proteins

    14
    Relative Entropy
    20 i
    H   pi pj s (i , j )
    i 1 j 1

    • Indicates power of scoring scheme to


    distinguish from “background noise” (i.e.,
    randomness)
    • Relative entropy of a random alignment
    should be negative
    • Can use H to compare different scoring
    matrices
    15
    Equivalent PAM and Blossum
    matrices (according to H)

    • PAM100 ==> Blosum90


    • PAM120 ==> Blosum80
    • PAM160 ==> Blosum60
    • PAM200 ==> Blosum52
    • PAM250 ==> Blosum45

    16
    PAM versus Blosum

    Source: http://www.csit.fsu.edu/~swofford/bioinformatics_spring05/lectures/lecture03-blosum.pdf 17
    Superiority of BLOSUM for database
    searches
    (according to Henikoff and Henikoff)

    18

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