Pairwise profile alignment

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