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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00753

MetaTOR recovers high-quality metagenome-assembled genomes (MAGs) from mammalian gut proximity-ligation (meta3C) libraries, regardless the number of samples

 Lyam Baudry1, 2,  Theo Foutel-Rodier1, 2, Agnès Thierry1, 2,  Romain Koszul1, 2* and  Martial Marbouty1, 2*
  • 1Institut Pasteur, France
  • 2UMR3525 Génétique des génomes, France

Characterizing the full genomic structure of complex microbial communities is a key step towards the understanding of their diversity, dynamics and evolution. These investigations are typically done through the analysis of millions of short DNA sequences directly extracted from the environment. Computational tools exploiting these metagenomics data display intrinsic limitations or constraints, such as assumptions regarding the genomic content of the genomes being investigated, and/or the need for multiple samples to accurately bin the interleaved metagenomic sequences according to their covariant characteristics. Here we present MetaTOR, an open-source and transparent computational solution that exploits meta3C, i.e. proximity ligation experiments (3C, Hi-C) performed on metagenomic samples, to bin the resulting sequencing reads into individual genomes according to their 3D contact frequencies. MetaTOR was applied on a combination of 20 newly generated meta3C libraries of mice gut microbiote sampled over time. We quantified the ability of the program to recover high-quality metagenomics-assembled metagenomes (MAGs) from metagenomics assemblies generated directly from the meta3C libraries. Whereas 16 MAGs are identified in the 148Mb assembly generated using a single meta3C library, MetaTOR identifies 122 MAGs in the 763Mb assembly generated from the merged 20 meta3C libraries, corresponding to a ~40% increase compared to MAGs recovered using current, state-of-the-art hybrid binning programs. Overall, the completion and contamination of meta3C bins were also improved. These results underline the potential of meta3C (and 3C based approaches) in metagenomics projects.

Keywords: gut microbiome, mouse gut microbiome, Proximity ligation, meta3C, Metagenomics binning, Metagenomics analysis, proximity ligation assay, Binning algorithm, Metagenome-assembled genomes (MAGs), Hi-C, chromosome conformation capture

Received: 17 Apr 2019; Accepted: 17 Jul 2019.

Edited by:

Bas E. Dutilh, Utrecht University, Netherlands

Reviewed by:

Digvijay Verma, Babasaheb Bhimrao Ambedkar University, India
Marnix H. Medema, Wageningen University & Research, Netherlands  

Copyright: © 2019 Baudry, Foutel-Rodier, Thierry, Koszul and Marbouty. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Romain Koszul, Institut Pasteur, Paris, 75015, Île-de-France, France, rkoszul@gmail.com
Mx. Martial Marbouty, Institut Pasteur, Paris, 75015, Île-de-France, France, martial.marbouty@pasteur.fr