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Nat Biotechnol. 2014 Aug;32(8):822-8. doi: 10.1038/nbt.2939. Epub 2014 Jul 6.

Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes.

Author information

1
1] Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. [2] Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark. [3].
2
1] INRA, Institut National de la Recherche Agronomique, UMR 14121 MICALIS, Jouy en Josas, France. [2] INRA, Institut National de la Recherche Agronomique, US 1367 Metagenopolis, Jouy en Josas, France. [3] Department of Computer Science, Center for Bioinformatics and Computational Biology, University of Maryland, USA. [4].
3
1] Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. [2] Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
4
Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark.
5
1] BGI Hong Kong Research Institute, Hong Kong, China. [2] BGI-Shenzhen, Shenzhen, China. [3] School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, China.
6
European Molecular Biology Laboratory, Heidelberg, Germany.
7
1] INRA, Institut National de la Recherche Agronomique, UMR 14121 MICALIS, Jouy en Josas, France. [2] INRA, Institut National de la Recherche Agronomique, US 1367 Metagenopolis, Jouy en Josas, France.
8
1] Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Génomique, Évry, France. [2] Centre National de la Recherche Scientifique, Évry, France. [3] Université d'Évry Val d'Essonne, Évry, France.
9
The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
10
Digestive System Research Unit, University Hospital Vall d'Hebron, Ciberehd, Barcelona, Spain.
11
1] BGI-Shenzhen, Shenzhen, China. [2] European Molecular Biology Laboratory, Heidelberg, Germany. [3] The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
12
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
13
1] The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. [2] Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
14
1] Department of Structural Biology, VIB, Brussels, Belgium. [2] Department of Bioscience Engineering, Vrije Universiteit, Brussels, Belgium.
15
National Food Institute, Division for Epidemiology and Microbial Genomics, Technical University of Denmark, Kongens Lyngby, Denmark.
16
1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
17
1] The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. [2] Hagedorn Research Institute, Gentofte, Denmark. [3] Institute of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [4] Faculty of Health, Aarhus University, Aarhus, Denmark.
18
1] BGI Hong Kong Research Institute, Hong Kong, China. [2] BGI-Shenzhen, Shenzhen, China.
19
1] Department of Bioscience Engineering, Vrije Universiteit, Brussels, Belgium. [2] Department of Microbiology and Immunology, Rega Institute, KU Leuven, Belgium. [3] VIB Center for the Biology of Disease, Leuven, Belgium.
20
Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
21
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
22
1] European Molecular Biology Laboratory, Heidelberg, Germany. [2] Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan.
23
INRA, Institut National de la Recherche Agronomique, UMR 14121 MICALIS, Jouy en Josas, France.
24
1] European Molecular Biology Laboratory, Heidelberg, Germany. [2] Max Delbrück Centre for Molecular Medicine, Berlin, Germany.
25
1] BGI-Shenzhen, Shenzhen, China. [2] The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. [3] Department of Biology, University of Copenhagen, Copenhagen, Denmark. [4] Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
26
1] INRA, Institut National de la Recherche Agronomique, UMR 14121 MICALIS, Jouy en Josas, France. [2] INRA, Institut National de la Recherche Agronomique, US 1367 Metagenopolis, Jouy en Josas, France. [3] King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, United Kingdom.

Abstract

Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.

PMID:
24997787
DOI:
10.1038/nbt.2939
[Indexed for MEDLINE]

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