Micro-Cm: restrictase-free microbiome-wide chromosome conformation profiling

Authors

Bermejo Ruiz, M., Wilhelm, C., Budde, H., Ley, R. E., Tyakht, A. V.

Abstract

Mobile genetic elements like plasmids, viruses and transposons can considerably augment the genomic repertoire of individual bacterial members of a complex multi-species microbiome and influence community dynamics. As linking a mobile element to its bacterial host based on metagenome sequencing alone proves challenging, such assays have been augmented with high-throughput chromosome conformation capture (Hi-C). However, the efficacy of Hi-C metagenomics is constrained by the protocol limitations and a lack of ground-truth reference datasets. In order to overcome these limitations, we present Micro-C metagenomics (Micro-Cm) - an adaptation of a superior, restrictase-free Micro-C technique for processing microbiome samples and mapping plasmid-host associations. We validated the developed experimental protocol and bioinformatic workflow on a simulated, defined consortium of diverse gut bacterial species and applied them to a long-read human gut microbiome sample. The proportion of valid reads in the synthetic community was an order of magnitude higher than that observed in multiple Hi-C metagenomic studies. For both samples, we obtained high-quality contact maps, which in the case of the synthetic community revealed fine-scale chromosome interactions. Moreover, successful recovery of plasmid-host interactions in the simulated community validated the method, which we then applied to the real stool sample. Our plasmid-host association analysis in a complex bacterial community successfully identified bacterial hosts for most of the identified complete plasmids. Our results show that Micro-Cm method improves profiling of complex microbiomes, exploration of mobile genetic element dynamics and community-wide, detailed investigation of chromosomal conformation patterns.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 13 Sep 2026.

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