A Generalized Lattice based Probabilistic Approach for Metagenomic Clustering

IEEE/ACM Trans Comput Biol Bioinform. 2017 Jul-Aug;14(4):749-761. doi: 10.1109/TCBB.2016.2563422. Epub 2016 May 5.

Abstract

Metagenomics involves the analysis of genomes of microorganisms sampled directly from their environment. Next Generation Sequencing allows a high-throughput sampling of small segments from genomes in the metagenome to generate reads. To study the properties and relationships of the microorganisms present, clustering can be performed based on the inherent composition of the sampled reads for unknown species. We propose a two-dimensional lattice based probabilistic model for clustering metagenomic datasets. The occurrence of a species in the metagenome is estimated using a lattice of probabilistic distributions over small sized genomic sequences. The two dimensions denote distributions for different sizes and groups of words respectively. The lattice structure allows for additional support for a node from its neighbors when the probabilistic support for the species using the parameters of the current node is deemed insufficient. We also show convergence for our algorithm. We test our algorithm on simulated metagenomic data containing bacterial species and observe more than 85% precision. We also evaluate our algorithm on an in vitro-simulated bacterial metagenome and on human patient data, and show a better clustering than other algorithms even for short reads and varied abundance. The software and datasets can be downloaded from https:// github.com/lattclus/lattice-metage.