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?

• 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

• 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

• ClustalW/MUSCLE – Let f be the profile vector

– Score(f,j)=

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

€

f i S(i, j)i∈{A ,C ,G,T}

∑

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

€

gi =f jPjqij

i∈{A ,C ,G,T}

∑

€

Qi =αf i + βgiα + β

(α ,β are constants)