Integrating sequence composition information into microbial diversity analyses with k-mer frequency counting

k-mers are all of the subsequences of length k that comprise a sequence. Comparing the frequency of k-mers in DNA sequences yields valuable information about the composition of these sequences and their similarity. This work demonstrates that k-mer frequencies from marker-gene sequence surveys can be used to inform diversity estimates and machine learning predictions that incorporate sequence composition information. Alpha and beta diversity estimates based on k-mer frequencies closely correspond to phylogenetically aware diversity metrics, suggesting that k-mer-based diversity estimates are useful proxy measurements especially when reliable phylogenies are not available, as is often the case for some DNA sequence targets such as for internal transcribed spacer sequences.