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Accurate and Complete Genomes from Metagenomes

View ORCID ProfileLin-Xing Chen, View ORCID ProfileKarthik Anantharaman, Alon Shaiber, View ORCID ProfileA. Murat Eren, View ORCID ProfileJillian F. Banfield
doi: https://doi.org/10.1101/808410
Lin-Xing Chen
1Department of Earth and Planetary Sciences, Berkeley, CA, USA
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Karthik Anantharaman
1Department of Earth and Planetary Sciences, Berkeley, CA, USA
7Department of Bacteriology, University of Wisconsin, Madison, WI, USA
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Alon Shaiber
2Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637, USA
3Department of Medicine, University of Chicago, Chicago 60637 IL, USA
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A. Murat Eren
3Department of Medicine, University of Chicago, Chicago 60637 IL, USA
4Bay Paul Center, Marine Biological Laboratory, Woods Hole 02543 MA, USA
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  • For correspondence: jbanfield@berkeley.edu a.murat.eren@gmail.com
Jillian F. Banfield
1Department of Earth and Planetary Sciences, Berkeley, CA, USA
5Department of Environmental Science, Policy, and Management, Berkeley, CA, USA
6Earth and Environmental Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
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  • For correspondence: jbanfield@berkeley.edu a.murat.eren@gmail.com
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Abstract

Genomes are an integral component of the biological information about an organism and, logically, the more complete the genome, the more informative it is. Historically, bacterial and archaeal genomes were reconstructed from pure (monoclonal) cultures and the first reported sequences were manually curated to completion. However, the bottleneck imposed by the requirement for isolates precluded genomic insights for the vast majority of microbial life. Shotgun sequencing of microbial communities, referred to initially as community genomics and subsequently as genome-resolved metagenomics, can circumvent this limitation by obtaining metagenome-assembled genomes (MAGs), but gaps, local assembly errors, chimeras and contamination by fragments from other genomes limit the value of these genomes. Here, we discuss genome curation to improve and in some cases achieve complete (circularized, no gaps) MAGs (CMAGs). To date, few CMAGs have been generated, although notably some are from very complex systems such as soil and sediment. Through analysis of ∼7000 published complete bacterial isolate genomes, we verify the value of cumulative GC skew in combination with other metrics to establish bacterial genome sequence accuracy. Interestingly, analysis of cumulative GC skew identified potential mis-assemblies in some reference genomes of isolated bacteria and the repeat sequences that likely gave rise to them. We discuss methods that could be implemented in bioinformatic approaches for curation to ensure that metabolic and evolutionary analyses can be based on very high-quality genomes.

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Posted October 17, 2019.
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Accurate and Complete Genomes from Metagenomes
Lin-Xing Chen, Karthik Anantharaman, Alon Shaiber, A. Murat Eren, Jillian F. Banfield
bioRxiv 808410; doi: https://doi.org/10.1101/808410
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Accurate and Complete Genomes from Metagenomes
Lin-Xing Chen, Karthik Anantharaman, Alon Shaiber, A. Murat Eren, Jillian F. Banfield
bioRxiv 808410; doi: https://doi.org/10.1101/808410

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