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Aligning Profile Vectors to Sequences in Protein Family Analysis

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This guide discusses the process of aligning profile vectors to sequences using standard dynamic programming, focusing on protein families. It covers creating a profile from family alignments, which can be used to identify new members in databases. By computing nucleotide or residue frequencies for each position in an alignment, a profile vector is generated. Subsequently, the alignment of this profile vector to a specific sequence is performed using methods such as ClustalW, MUSCLE, and PSI-BLAST. The scoring of alignments relies on substitution scoring matrices and background probabilities.

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Aligning Profile Vectors to Sequences in Protein Family Analysis

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  1. Pairwise profile alignment Usman Roshan BNFO 601

  2. Protein families • PFAM: http://pfam.sanger.ac.uk/ • Family alignments can be used to search for new members in a database

  3. 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.

  4. 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

  5. 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

  6. 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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