New, improved, and practical k-stem sequence similarity measures for probe design.

We define new measures of sequence similarity for oligonucleotide probe design. These new measures incorporate the nearest neighbor k-stem motifs in their definition, but can be efficiently computed by means of a bit-vector method. They are not as computationally costly as algorithms that predict nearest neighbor hybridization potential. Our new measures for sequence similarity correlate significantly better with nearest neighbor thermodynamic predictions than either BLAST or the standard edit or insertion-deletion defined similarities already in use in many different probe design applications.