The Metagenomic Binning Problem: Clustering Markov Sequences

The goal of metagenomics is to study the composition of microbial communities, typically using high-throughput shotgun sequencing. In the metagenomic binning problem, we observe random substrings (called contigs) from a mixture of genomes and aim to cluster them according to their genome of origin. Based on the empirical observation that genomes of different bacterial species can be distinguished based on their tetranucleotide frequencies, we model this task as the problem of clustering
${N}$
sequences generated by
${M}$
distinct Markov processes, where
$M \ll N$
. Utilizing the large-deviation principle for Markov processes, we establish the information-theoretic limit for perfect binning. Specifically, we show that the length of the contigs must scale with the inverse of the Chernoff divergence rate between the two most similar species. Furthermore, our result implies that contigs should be binned using the KL divergence rate as a measure of distance, as opposed to the Euclidean distance often used in practice.