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

Journal Article · · G3
 [1];  [2];  [2];  [2]
  1. Univ. of Washington, Seattle, WA (United States). Dept. of Genome Sciences; DOE/OSTI
  2. Univ. of Washington, Seattle, WA (United States). Dept. of Genome Sciences

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1627950
Journal Information:
G3, Journal Name: G3 Journal Issue: 7 Vol. 4; ISSN 2160-1836
Publisher:
Genetics Society of AmericaCopyright Statement
Country of Publication:
United States
Language:
English

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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 journal July 2015
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Additional file 3 of Expressions of resistome is linked to the key functions and stability of active rumen microbiome dataset January 2022
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Additional file 3 of The genomes of Vischeria oleaginous microalgae shed light on the molecular basis of hyper-accumulation of lipids dataset January 2023
Deconvoluting simulated metagenomes: the performance of hard- and soft- clustering algorithms applied to metagenomic chromosome conformation capture (3C) posted_content May 2016
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