1. Pairwise profile alignment Usman Roshan BNFO 601

2. Protein families PFAM: http://pfam.sanger.ac.uk/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(Q i /P i ) P i is the background probability of nucleotide i q ij is a matrix of match/mismatch probabilities Define g i as and Q i as