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Accurate and complete genomes from metagenomes

2020· review· en· 403 citations· W3011678041 on OpenAlex· 10.1101/gr.258640.119

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Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

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Opus teacher head0.219
GPT teacher head0.410
Teacher spread
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Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Genomes are an integral component of the biological information about an organism; thus, 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 about 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. The analysis of cumulative GC skew identified potential misassemblies 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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The record

Venue
Genome Research
Topic
Genomics and Phylogenetic Studies
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
Biological and Environmental ResearchNational Institute of Allergy and Infectious DiseasesLawrence Berkeley National LaboratoryNational Institute of General Medical SciencesOffice of ScienceNational Institutes of HealthInnovative Genomics InstituteGenome CanadaUniversity of California BerkeleyU.S. Department of Energy
Keywords
GenomeBiologyMetagenomicsBacterial genome sizeComputational biologyGenomicsShotgun sequencingGeneticsSequence assemblyGeneTranscriptome
Has abstract in OpenAlex
yes