Comparing sequences without alignment

Few generally available programs allow the flexible investigation of alternative alignments. A way of avoiding the problem is to make use of one of the earliest methods of comparing two sequences, the `dot-plot', or diagonal plot [Gibbs & McIntyre, 1970,Staden, 1982]. Although the dot-plot does not give an alignment directly, it is an effective technique to view simultaneously all similarities between two sequences. Similarities may be obvious in a dot-plot, but missed entirely by a dynamic programming sequence alignment program that only displays the top scoring alignment.

For two sequences A and B of length m and n respectively, a matrix D_m,n is generated where each element D_i,j represents the similarity between sequence segments centred on A_i and B_j. In its simplest form, D_i,j = 1 if A_i = B_j and D_i,j = 0 if $A_{i} \neq B_{j}$. A graph is plotted with A and B on each axis and a dot plotted whenever D_i,j > 0. Regions of sequence similarity appear as diagonal lines on the plot and repeats as parallel lines. Insertions and deletions show up as steps in the diagonals as the diagonal moves from one diagonal to another. The most sophisticated dot-plot techniques calculate D_i,j from a sliding window, and score similarities by a pair-score matrix such as BLOSUM62 or PAM250. Dotter [Sonnhammer & Durbin, 1995] provides a particularly rich set of features including an interactive dot-plot `contrast' adjustment that simplifies the interpretation of plots.