Genome 540 Homework Assignment 5

Due Sunday Feb. 15

1. Write a program that reads in three input protein sequences (from a FASTA file), together with a score matrix, creates the edit graph for the three sequences, and outputs this graph in a file in the appropriate input format for the WDAG program you wrote in part 1 of homework 4. Recall that, in the edit graph, vertices correspond to triples (i,j,k) where 0 <= i <= n1, 0 <= j <= n2, and 0 <= k <= n3, where n1, n2 and n3 are the lengths of the three sequences. There is an edge from (i,j,k) to (i',j',k') whenever i' = i or i+1, j' = j or j+1, and k' = k or k+1, and at least one of the equalities i'=i, j'=j, and k'=k is false. The label you should attach to an edge is the corresponding column of aligned residues & gap characters -- except that you can write it horizontally instead of vertically. For example, the label associated to the edge from (10,37,5) to (11,37,6) would be V-C if V is the 11th residue in the first sequence and C is the 6th residue in the third sequence. Note that different edges in the graph can have the same label.

   The weights attached to an edge should be the 'sum of pairs' weights. Specifically, each edge is labelled by 3 characters, say x_1, x_2, x_3, which may be residues or gap characters. There are 3 different unordered pairs of these characters, namely (x_1, x_2), (x_1, x_3) and (x_2, x_3). The weight attached to the edge is then the sum of the 3 pair weights, where the weight of (x_i, x_j) is

   • the corresponding score matrix entry if x_i and x_j are both residues;
   • the gap penalty if one of x_i and x_j is a residue, and the other is a gap character
   • 0 if both x_i and x_j are gap characters
2. Run your program to produce an output file giving the edit graph for the following three sequences:

   >HBB_PROLO   hemoglobin beta chain - raccoon
   VHLTADEKTAVTTLWGKVNVEEVGGEALGRLLVVYPWTQRFFESFGDLSSADAIMGNPKVKAHGKKVLNS
   FSEGLKNLDNLKGTFAKLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANA
   LAHKYH
   >HBA_TRAST  hemoglobin alpha chain - greater kudu
   LSAADKGHVKAAWGKVGSHAAEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGAKVAAALTKAVD
   HLDDLPGALSDLSDLHAHKLRVDPVNFKLLSHSLLVTLASHLPGDFTPAVHASLDKFLANVSTVLTSKYR
   >HBAM_RANCA  hemoglobin alpha-type chain, cardiac muscle - bullfrog
   GLSDSEKSAVASLWEKIAPQTNKLGAESMERLFKNHPETKSFFSRFDISPGSQDLLTHGGKIFGALGEAI
   KSLDNLQKYQDLHTNKLKLSSDHMKLLSAAIIEVFTAHFGGEVNQAAWNKFLGEVGAILTSS
   

   using the BLOSUM62 score matrix for the pairwise scores:

      A  R  N  D  C  Q  E  G  H  I  L  K  M  F  P  S  T  W  Y  V  B  Z  X  *
   A  4 -1 -2 -2  0 -1 -1  0 -2 -1 -1 -1 -1 -2 -1  1  0 -3 -2  0 -2 -1  0 -4 
   R -1  5  0 -2 -3  1  0 -2  0 -3 -2  2 -1 -3 -2 -1 -1 -3 -2 -3 -1  0 -1 -4 
   N -2  0  6  1 -3  0  0  0  1 -3 -3  0 -2 -3 -2  1  0 -4 -2 -3  3  0 -1 -4 
   D -2 -2  1  6 -3  0  2 -1 -1 -3 -4 -1 -3 -3 -1  0 -1 -4 -3 -3  4  1 -1 -4 
   C  0 -3 -3 -3  9 -3 -4 -3 -3 -1 -1 -3 -1 -2 -3 -1 -1 -2 -2 -1 -3 -3 -2 -4 
   Q -1  1  0  0 -3  5  2 -2  0 -3 -2  1  0 -3 -1  0 -1 -2 -1 -2  0  3 -1 -4 
   E -1  0  0  2 -4  2  5 -2  0 -3 -3  1 -2 -3 -1  0 -1 -3 -2 -2  1  4 -1 -4 
   G  0 -2  0 -1 -3 -2 -2  6 -2 -4 -4 -2 -3 -3 -2  0 -2 -2 -3 -3 -1 -2 -1 -4 
   H -2  0  1 -1 -3  0  0 -2  8 -3 -3 -1 -2 -1 -2 -1 -2 -2  2 -3  0  0 -1 -4 
   I -1 -3 -3 -3 -1 -3 -3 -4 -3  4  2 -3  1  0 -3 -2 -1 -3 -1  3 -3 -3 -1 -4 
   L -1 -2 -3 -4 -1 -2 -3 -4 -3  2  4 -2  2  0 -3 -2 -1 -2 -1  1 -4 -3 -1 -4 
   K -1  2  0 -1 -3  1  1 -2 -1 -3 -2  5 -1 -3 -1  0 -1 -3 -2 -2  0  1 -1 -4 
   M -1 -1 -2 -3 -1  0 -2 -3 -2  1  2 -1  5  0 -2 -1 -1 -1 -1  1 -3 -1 -1 -4 
   F -2 -3 -3 -3 -2 -3 -3 -3 -1  0  0 -3  0  6 -4 -2 -2  1  3 -1 -3 -3 -1 -4 
   P -1 -2 -2 -1 -3 -1 -1 -2 -2 -3 -3 -1 -2 -4  7 -1 -1 -4 -3 -2 -2 -1 -2 -4 
   S  1 -1  1  0 -1  0  0  0 -1 -2 -2  0 -1 -2 -1  4  1 -3 -2 -2  0  0  0 -4 
   T  0 -1  0 -1 -1 -1 -1 -2 -2 -1 -1 -1 -1 -2 -1  1  5 -2 -2  0 -1 -1  0 -4 
   W -3 -3 -4 -4 -2 -2 -3 -2 -2 -3 -2 -3 -1  1 -4 -3 -2 11  2 -3 -4 -3 -2 -4 
   Y -2 -2 -2 -3 -2 -1 -2 -3  2 -1 -1 -2 -1  3 -3 -2 -2  2  7 -1 -3 -2 -1 -4 
   V  0 -3 -3 -3 -1 -2 -2 -3 -3  3  1 -2  1 -1 -2 -2  0 -3 -1  4 -3 -2 -1 -4 
   B -2 -1  3  4 -3  0  1 -1  0 -3 -4  0 -3 -3 -2  0 -1 -4 -3 -3  4  1 -1 -4 
   Z -1  0  0  1 -3  3  4 -2  0 -3 -3  1 -1 -3 -1  0 -1 -3 -2 -2  1  4 -1 -4 
   X  0 -1 -1 -1 -2 -1 -1 -1 -1 -1 -1 -1 -1 -1 -2  0  0 -2 -1 -1 -1 -1 -1 -4 
   * -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4  1 
   
   Gap penalty: -6
   

   Then run your WDAG program from homework # 4 on this file, using the second output option (that prints the labels on all the edges in the path, in order) to produce a highest scoring path (and its score) giving a highest-scoring alignment of the three sequences; & send me and Chris the results.