D2Z is based on comparing the frequencies of all fixed-length words in the two sequences. An important, novel feature of the score is that it is comparable across sequence pairs drawn from arbitrary background distributions.
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A statistical method for alignment-free comparison of regulatory sequences
Miriam R. Kantorovitz,Gene E. Robinson, Saurabh Sinha.
Bioinformatics. 2007 Jul 1;23(13):i249-55.