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Viterbi is an algorithm for finding the maximum likelihood assignment to the hidden variables of an HMM, given the observed variables (we know the transition and emission probabilities of the HMM). However, the dynamic programming algorithm that finds the best alignment between two strings (Smith-Waterman), is also referred to as Viterbi. I'm trying to understand why Smith-Waterman is an instantiation of Viterbi. Specifically, what is the HMM that represents the alignment problem, what are the possible values for the hidden variables, what are the emission probabilities for each hidden variable, and what is the observed data. Can you help me see the correspondence?

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Added bioinformatics flag b/c of the typical context. –  Steve Huntsman Jan 29 '10 at 1:09

2 Answers 2

Consider the problem of finding the best score rather than the item that achieves the best score. Then both of these algorithms are matrix multplications in the tropical semiring. In other words they can be written as matrix multiplications over the reals union $\infty$, where the usual $+$ operation is replaced by $\min$ and multiplication is replaced by $+$. (You may need to think in terms of log probabilities to see the correspondence.)

You can see this by looking at the innermost loops of both algorithms. For example, the viterbi algorithm code at wikipedia has the $\min$ of a bunch of "emit_p[source_state][output] * trans_p[source_state][next_state]" in its innermost loop, just like the $a_{ij}b_{jk}$ in the definition of matrix multiplication. Similarly, if you look at the wikipedia edit distance algorithm the core work is done by a line "d[i, j] := minimum(d[i-1, j] + 1, d[i, j-1] + 1, d[i-1, j-1] + 1)". Again it's the $\min$ of a bunch of sums.

In fact, I wrote one piece of code code to implement both edit distance and Viterbi a while back. Unfortunately that article's probably gobblydegook if you don't know Haskell, but the text around the diagrams may be helpful.

(I should have made clear first time, edit distance and Smith-Waterman are pretty much the same thing, just with different weights.)

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Thanks for the comment, but I couldn't really see the correspondence. To be more specific, what would help me is to know what I should plug into "emit_p", "trans_p" and "output" in the code for the Viterbi algorithm in order to get an alignment between two given strings, x and y. –  Jonathan Jan 29 '10 at 7:12

A HMM for local alignment is shown at

http://books.google.com/books?id=R5P2GlJvigQC&pg=PA86

EDIT It's been 7 or 8 years since I really understood this stuff, but I have some old MATLAB code that implements Smith-Waterman. Since a cursory search doesn't show any such code, I figured I'd post it here. Although I don't think this is what you're really asking for, perhaps it will help you (or someone else).

function y=smithwatbl50lin(D1,D2)
% Smith-Waterman alignment of two ssDNAs 
% (OR RNAS: U is equivalent to T here)
% with 5-3 ([uppercase] char) strand D*
% Uses the BLOSUM50 matrix and linear gap penalty. 
% Alignment is done randomly (in that
% the traceback goes uniformly at random
% when it's got more than one possibility)

% As usual with my code, there's little room for error...

D1(find(D1=='U'))='T';
D2(find(D2=='U'))='T';

% BLOSUM50 matrix (use symmetry to minimize number of entries typed by hand)
bl50(1,1:20) = [5  -2 -1 -2 -1 -1 -1  0 -2 -1 -2 -1 -1 -3 -1  1  0 -3 -2  0];
bl50(2,2:20) = [7  -1 -2 -4  1  0 -3  0 -4 -3  3 -2 -3 -3 -1 -1 -3 -1 -3];
bl50(3,3:20) = [7   2 -2  0  0  0  1 -3 -4  0 -2 -4 -2  1  0 -4 -2 -3];
bl50(4,4:20) = [8  -4  0  2 -1 -1 -4 -4 -1 -4 -5 -1  0 -1 -5 -3 -4];
bl50(5,5:20) = [13 -3 -3 -3 -3 -2 -2 -3 -2 -2 -4 -1 -1 -5 -3 -1];
bl50(6,6:20) = [7   2 -2  1 -3 -2  2  0 -4 -1  0 -1 -1 -1 -3];
bl50(7,7:20) = [6  -3  0 -4 -3  1 -2 -3 -1 -1 -1 -3 -2 -3];
bl50(8,8:20) = [8  -2 -4 -4 -2 -3 -4 -2  0 -2 -3 -3 -4];
bl50(9,9:20) = [10 -4 -3  0 -1 -1 -2 -1 -2 -3  2 -4];
bl50(10,10:20)=[5   2 -3  2  0 -3 -3 -1 -3 -1  4];
bl50(11,11:20)=[5  -3  3  1 -4 -3 -1 -2 -1  1];
bl50(12,12:20)=[6  -2 -4 -1  0 -1 -3 -2 -3];
bl50(13,13:20)=[7   0 -3 -2 -1 -1  0  1];
bl50(14,14:20)=[8  -4  3 -2  1  4 -1];
bl50(15,15:20)=[10 -1 -1 -4 -3 -3];
bl50(16,16:20)=[5   2 -4 -2 -2];
bl50(17,17:20)=[5  -3 -2  0];
bl50(18,18:20)=[15  2 -3];
bl50(19,19:20)=[8  -1];
bl50(20,20)=5;
bl50=bl50+triu(bl50,1)';

% linear gap penalty
d=8;

% get integral character arrays
E1(D1=='A')='0';
E1(D1=='C')='1';
E1(D1=='G')='2';
E1(D1=='T')='3';
E2(D2=='A')='0';
E2(D2=='C')='1';
E2(D2=='G')='2';
E2(D2=='T')='3';

r=length(E1);
c=length(E2);

% translate to codons, dropping any possible end garbage
E1=E1(1:3*floor(r/3));
E2=E2(1:3*floor(c/3));
% Amino acid hash assigments
%  A  R  N  D  C  Q  E  G  H  I  L  K  M  F  P  S  T  W  Y  V
%  1  2  3  4  5  6  7  8  9 10 11 12 13 14 15 16 17 18 19 20
% Term --> 21
% List codons in alphabetical order (which equates to
% setting A=0, C=1, G=2, T=3 as we do above and using numerical order)
% and then hash to get
aha=[12 3 12 3 17 17 17 17 2 16 2 16 10 10 13 10];
ahc=[6 9 6 9 15 15 15 15 2 2 2 2 11 11 11 11];
ahg=[7 4 7 4 1 1 1 1 8 8 8 8 20 20 20 20];
aht=[21 19 21 19 16 16 16 16 21 5 18 5 11 14 11 14];
aminohash=[aha ahc ahg aht];
% NB. This will keep us from using zillions (ok, 64) if statements
% Now we're making polypeptides, terminating at the first 21 found
for codon=1:floor(r/3)
    ah=aminohash( base2dec(E1(3*(codon-1)+1:3*codon),4) + 1);
    if ah==21
        break;
    end
    PP1(codon)=ah;
end
for codon=1:floor(c/3)
    ah=aminohash( base2dec(E2(3*(codon-1)+1:3*codon),4) + 1);
    if ah==21
        break;
    end
    PP2(codon)=ah;
end

LPP1=length(PP1);
LPP2=length(PP2);

F=zeros(LPP1+1,LPP2+1);
traceback=zeros(LPP1+1,LPP2+1);
% raster-fill F...
for i=2:LPP1+1
    for j=2:LPP2+1
        temp1=F(i,j-1)-d; % left
        temp2=F(i-1,j)-d; % up
        temp3=F(i-1,j-1)+bl50(PP1(i-1),PP2(j-1)); % left and up
        temp{i,j}=[0 temp1 temp2 temp3];
        F(i,j)=max(temp{i,j});
        temp4=find(temp{i,j}==F(i,j));
        traceback(i,j)=temp4(ceil(rand*length(temp4)));
        clear temp4;
    end
end


iah='ARNDCQEGHILKMFPSTWYV'; % inverse amino hash string

% Find the biggest score entry. If several than pick one uniformly at random
mf=max(max(F));
tempf=find(F==mf);
[mfi,mfj]=ind2sub(size(F),tempf(ceil(rand*length(tempf))));

% in the end we'll flip alignment--REMEMBER!
backtrace=[mfi,mfj];
if F(backtrace(1),backtrace(2))==0
    'no local alignment'
    break;
elseif traceback(backtrace(1),backtrace(2))-1==3
    alignment(:,1)=[iah(PP1(backtrace(1)-1));' ';iah(PP2(backtrace(2)-1))];
    backtrace=backtrace-[1 1];
elseif traceback(backtrace(1),backtrace(2))-1==2
    alignment(:,1)=[iah(PP1(backtrace(1)-1));' ';'-'];
    backtrace=backtrace-[1 0];
elseif traceback(backtrace(1),backtrace(2))-1==1
    alignment(:,1)=['-';' ';iah(PP2(backtrace(2)-1))];
    backtrace=backtrace-[0 1];
end

k=1;    
while max(backtrace>1)
    k=k+1;
    if F(backtrace(1),backtrace(2))==0
        break;
    elseif traceback(backtrace(1),backtrace(2))-1==3
        alignment(:,k)=[iah(PP1(backtrace(1)-1));' ';iah(PP2(backtrace(2)-1))];
        backtrace=backtrace-[1 1];
    elseif traceback(backtrace(1),backtrace(2))-1==2
        alignment(:,k)=[iah(PP1(backtrace(1)-1));' ';'-'];
        backtrace=backtrace-[1 0];
    elseif traceback(backtrace(1),backtrace(2))-1==1
        alignment(:,k)=['-';' ';iah(PP2(backtrace(2)-1))];
        backtrace=backtrace-[0 1];
    else
        break;
    end
end

alignment=fliplr(alignment);

la=size(alignment,2);
for i=1:la
    if alignment(1,i)==alignment(3,i)
        alignment(2,i)=alignment(1,i);
    elseif bl50(min(find(iah==alignment(1,i))),min(find(iah==alignment(3,i))))>0
        alignment(2,i)='+';
    else
        alignment(2,i)=' ';
    end
end

y=alignment;
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Yes, I have that book, and this is exactly where I lost them. The "observed nodes" in the HMM in that figure are matching pairs of letters. Given the observations it is trivial to infer the hidden nodes: if the observed value is two letters - it's an M state. Otherwise (the observed value is a letter and a dash) the state is an X state or a Y state, depending where the dash is. But in the alignment problem the strings are given without an alignment. How can you plug it in to the above HMM in order to run Viterbi on it? –  Jonathan Jan 29 '10 at 7:07

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