Ranked k-spectrum kernel for comparative and evolutionary comparison of exons, introns, and CpG islands.

Existing k-mer based string kernel methods have been successfully used for sequence comparison. However, existing kernel methods have limitations for comparative and evolutionary comparisons of genomes due to the sensitiveness to over-represented k-mers and variable sequence lengths.In this study, we propose a novel ranked k-spectrum string (RKSS) kernel. 1) RKSS kernel utilizes common k-mer sets across species, named landmarks, that can be used for comparing multiple genomes. 2) Based on the landmarks, we can use ranks of k-mers, rather than frequencies, that can produce more robust distances between genomes. To show the power of RKSS kernel, we conducted two experiments using 10 mammalian species with exon, intron, and CpG island sequences. RKSS kernel reconstructed more consistent evolutionary trees than the k-spectrum string kernel. In the subsequent experiment, for each sequence, kernel distance was calculated from 30 landmarks representing exon, intron, and CpG island sequences of 10 genomes. Based on kernel distances, concordance tests were performed and the result suggested that more information is conserved in CpG islands across species than in introns. In conclusion, our analysis suggests that the relational order, exon > CpG island > intron, in terms of evolutionary information contents.