Pairwise profile alignment
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Pairwise profile alignment. Usman Roshan BNFO 601. Protein families. PFAM: http://pfam.sanger.ac.uk/ Family alignments can be used to search for new members in a database. Profile-sequence alignment. Given a family alignment, how can we align it to a sequence?

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Pairwise profile alignment

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Pairwise profile alignment

Pairwise profile alignment

Usman Roshan

BNFO 601


Protein families

Protein families

  • PFAM: http://pfam.sanger.ac.uk/

  • Family alignments can be used to search for new members in a database


Profile sequence alignment

Profile-sequence alignment

  • Given a family alignment, how can we align it to a sequence?

  • First, we compute a profile of the alignment.

  • We then align the profile to the sequence using standard dynamic programming.

  • However, we need to describe how to align a profile vector to a nucleotide or residue.


Profile

Profile

  • A profile can be described by a set of vectors of nucleotide/residue frequencies.

  • For each position i of the alignment, we we compute the normalized frequency of nucleotides A, C, G, and T


Aligning a profile vector to a nucleotide

Aligning a profile vector to a nucleotide

  • ClustalW/MUSCLE

    • Let f be the profile vector

    • Score(f,j)=

    • where S(i,j) is substitution scoring matrix


Aligning a profile vector to a nucleotide1

Aligning a profile vector to a nucleotide

  • PSI-BLAST

  • Score(f,i)=log(Qi/Pi)

  • Pi is the background probability of nucleotide i

  • qij is a matrix of match/mismatch probabilities

  • Define gi as

  • and Qi as


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