Species-Level Deconvolution of Metagenome Assemblies with Hi-C–Based Contact Probability Maps

Abstract

Microbial communities consist of mixed populations of organisms, including unknown species in unknown abundances. These communities are often studied through metagenomic shotgun sequencing, but standard library construction methods remove long-range contiguity information; thus, shotgun sequencing and de novo assembly of a metagenome typically yield a collection of contigs that cannot readily be grouped by species. Methods for generating chromatin-level contact probability maps, e.g., as generated by the Hi-C method, provide a signal of contiguity that is completely intracellular and contains both intrachromosomal and interchromosomal information. Here, we demonstrate how this signal can be exploited to reconstruct the individual genomes of microbial species present within a mixed sample. We apply this approach to two synthetic metagenome samples, successfully clustering the genome content of fungal, bacterial, and archaeal species with more than 99% agreement with published reference genomes. We also show that the Hi-C signal can secondarily be used to create scaffolded genome assemblies of individual eukaryotic species present within the microbial community, with higher levels of contiguity than some of the species’ published reference genomes.

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Cited by papers we hold 9

• Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C · 2020
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• bin3C: exploiting Hi-C sequencing data to accurately resolve metagenome-assembled genomes · 2019
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• Linking the resistome and plasmidome to the microbiome · 2019
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• Evaluating the Information Content of Shallow Shotgun Metagenomics · 2018
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• Assembly of 913 microbial genomes from metagenomic sequencing of the cow rumen · 2018
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• Analysis methods for studying the 3D architecture of the genome · 2015
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• A Year of Infection in the Intensive Care Unit: Prospective Whole Genome Sequencing of Bacterial Clinical Isolates Reveals Cryptic Transmissions and Novel Microbiota · 2015
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• Computational approaches to predict bacteriophage–host relationships · 2015
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• Metagenomic chromosome conformation capture (meta3C) unveils the diversity of chromosome organization in microorganisms · 2014
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