pairwise profile alignment
DESCRIPTION
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? - PowerPoint PPT PresentationTRANSCRIPT
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)