PMID- 24997787 OWN - NLM STAT- MEDLINE DCOM- 20150413 LR - 20240109 IS - 1546-1696 (Electronic) IS - 1087-0156 (Linking) VI - 32 IP - 8 DP - 2014 Aug TI - Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. PG - 822-8 LID - 10.1038/nbt.2939 [doi] AB - 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. FAU - Nielsen, H Bjorn AU - Nielsen HB AD - 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]. FAU - Almeida, Mathieu AU - Almeida M AD - 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]. FAU - Juncker, Agnieszka Sierakowska AU - Juncker AS AD - 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. FAU - Rasmussen, Simon AU - Rasmussen S AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Li, Junhua AU - Li J AD - 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. FAU - Sunagawa, Shinichi AU - Sunagawa S AD - European Molecular Biology Laboratory, Heidelberg, Germany. FAU - Plichta, Damian R AU - Plichta DR AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Gautier, Laurent AU - Gautier L AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Pedersen, Anders G AU - Pedersen AG AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Le Chatelier, Emmanuelle AU - Le Chatelier E AD - 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. FAU - Pelletier, Eric AU - Pelletier E AD - 1] Commissariat a l'Energie Atomique et aux Energies Alternatives, Institut de Genomique, Evry, France. [2] Centre National de la Recherche Scientifique, Evry, France. [3] Universite d'Evry Val d'Essonne, Evry, France. FAU - Bonde, Ida AU - Bonde I AD - 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. FAU - Nielsen, Trine AU - Nielsen T AD - The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. FAU - Manichanh, Chaysavanh AU - Manichanh C AD - Digestive System Research Unit, University Hospital Vall d'Hebron, Ciberehd, Barcelona, Spain. FAU - Arumugam, Manimozhiyan AU - Arumugam M AUID- ORCID: 0000000208869101 AD - 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. FAU - Batto, Jean-Michel AU - Batto JM AD - 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. FAU - Quintanilha Dos Santos, Marcelo B AU - Quintanilha Dos Santos MB AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Blom, Nikolaj AU - Blom N AD - Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Borruel, Natalia AU - Borruel N AD - Digestive System Research Unit, University Hospital Vall d'Hebron, Ciberehd, Barcelona, Spain. FAU - Burgdorf, Kristoffer S AU - Burgdorf KS AD - The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. FAU - Boumezbeur, Fouad AU - Boumezbeur F AD - 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. FAU - Casellas, Francesc AU - Casellas F AD - Digestive System Research Unit, University Hospital Vall d'Hebron, Ciberehd, Barcelona, Spain. FAU - Dore, Joel AU - Dore J AD - 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. FAU - Dworzynski, Piotr AU - Dworzynski P AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Guarner, Francisco AU - Guarner F AD - Digestive System Research Unit, University Hospital Vall d'Hebron, Ciberehd, Barcelona, Spain. FAU - Hansen, Torben AU - Hansen T AD - 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. FAU - Hildebrand, Falk AU - Hildebrand F AD - 1] Department of Structural Biology, VIB, Brussels, Belgium. [2] Department of Bioscience Engineering, Vrije Universiteit, Brussels, Belgium. FAU - Kaas, Rolf S AU - Kaas RS AD - National Food Institute, Division for Epidemiology and Microbial Genomics, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Kennedy, Sean AU - Kennedy S AD - 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. FAU - Kristiansen, Karsten AU - Kristiansen K AD - 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark. FAU - Kultima, Jens Roat AU - Kultima JR AD - European Molecular Biology Laboratory, Heidelberg, Germany. FAU - Leonard, Pierre AU - Leonard P AD - 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. FAU - Levenez, Florence AU - Levenez F AD - 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. FAU - Lund, Ole AU - Lund O AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Moumen, Bouziane AU - Moumen B AD - 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. FAU - Le Paslier, Denis AU - Le Paslier D AD - 1] Commissariat a l'Energie Atomique et aux Energies Alternatives, Institut de Genomique, Evry, France. [2] Centre National de la Recherche Scientifique, Evry, France. [3] Universite d'Evry Val d'Essonne, Evry, France. FAU - Pons, Nicolas AU - Pons N AD - 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. FAU - Pedersen, Oluf AU - Pedersen O AD - 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. FAU - Prifti, Edi AU - Prifti E AD - 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. FAU - Qin, Junjie AU - Qin J AD - 1] BGI Hong Kong Research Institute, Hong Kong, China. [2] BGI-Shenzhen, Shenzhen, China. FAU - Raes, Jeroen AU - Raes J AD - 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. FAU - Sorensen, Soren AU - Sorensen S AD - Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark. FAU - Tap, Julien AU - Tap J AD - European Molecular Biology Laboratory, Heidelberg, Germany. FAU - Tims, Sebastian AU - Tims S AD - Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands. FAU - Ussery, David W AU - Ussery DW AD - Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark. FAU - Yamada, Takuji AU - Yamada T AD - 1] European Molecular Biology Laboratory, Heidelberg, Germany. [2] Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan. CN - MetaHIT Consortium FAU - Renault, Pierre AU - Renault P AD - INRA, Institut National de la Recherche Agronomique, UMR 14121 MICALIS, Jouy en Josas, France. FAU - Sicheritz-Ponten, Thomas AU - Sicheritz-Ponten T AD - 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. FAU - Bork, Peer AU - Bork P AD - 1] European Molecular Biology Laboratory, Heidelberg, Germany. [2] Max Delbruck Centre for Molecular Medicine, Berlin, Germany. FAU - Wang, Jun AU - Wang J AD - 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. FAU - Brunak, Soren AU - Brunak S AD - 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. FAU - Ehrlich, S Dusko AU - Ehrlich SD AD - 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. CN - MetaHIT Consortium LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140706 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 SB - IM MH - Cluster Analysis MH - Databases, Genetic MH - *Metagenomics FIR - Nielsen, H Bjorn IR - Nielsen HB FIR - Almeida, Mathieu IR - Almeida M FIR - Juncker, Agnieszka S IR - Juncker AS FIR - Rasmussen, Simon IR - Rasmussen S FIR - Li, Junhua IR - Li J FIR - Sunagawa, Shinichi IR - Sunagawa S FIR - Plichta, Damian R IR - Plichta DR FIR - Gautier, Laurent IR - Gautier L FIR - Pedersen, Anders G IR - Pedersen AG FIR - Le Chatelier, Emmanuelle IR - Le Chatelier E FIR - Pelletier, Eric IR - Pelletier E FIR - Bonde, Ida IR - Bonde I FIR - Nielsen, Trine IR - Nielsen T FIR - Manichanh, Chaysavanh IR - Manichanh C FIR - Arumugam, Manimozhiyan IR - Arumugam M FIR - Batto, Jean-Michel IR - Batto JM FIR - Quintanilha Dos Santos, Marcelo B IR - Quintanilha Dos Santos MB FIR - Blom, Nikolaj IR - Blom N FIR - Borruel, Natalia IR - Borruel N FIR - Burgdorf, Kristoffer S IR - Burgdorf KS FIR - Boumezbeur, Fouad IR - Boumezbeur F FIR - Casellas, Francesc IR - Casellas F FIR - Dore, Joel IR - Dore J FIR - Dworzynski, Piotr IR - Dworzynski P FIR - Guarner, Francisco IR - Guarner F FIR - Hansen, Torben IR - Hansen T FIR - Hildebrand, Falk IR - Hildebrand F FIR - Kaas, Rolf S IR - Kaas RS FIR - Kennedy, Sean IR - Kennedy S FIR - Kristiansen, Karsten IR - Kristiansen K FIR - Kultima, Jens Roat IR - Kultima JR FIR - Leonard, Pierre IR - Leonard P FIR - Levenez, Florence IR - Levenez F FIR - Lund, Ole IR - Lund O FIR - Moumen, Bouziane IR - Moumen B FIR - Le Paslier, Denis IR - Le Paslier D FIR - Pons, Nicolas IR - Pons N FIR - Pedersen, Oluf IR - Pedersen O FIR - Prifti, Edi IR - Prifti E FIR - Qin, Junjie IR - Qin J FIR - Raes, Jeroen IR - Raes J FIR - Sorensen, Soren IR - Sorensen S FIR - Tap, Julien IR - Tap J FIR - Tims, Sebastian IR - Tims S FIR - Ussery, David W IR - Ussery DW FIR - Yamada, Takuji IR - Yamada T FIR - Renault, Pierre IR - Renault P FIR - Sicheritz-Ponten, Thomas IR - Sicheritz-Ponten T FIR - Bork, Peer IR - Bork P FIR - Wang, Jun IR - Wang J FIR - Brunak, Soren IR - Brunak S FIR - Ehrlich, S Dusko IR - Ehrlich SD FIR - Jamet, Alexandre IR - Jamet A FIR - Merieux, Alexandre IR - Merieux A FIR - Cultrone, Antonella IR - Cultrone A FIR - Torrejon, Antonio IR - Torrejon A FIR - Quinquis, Benoit IR - Quinquis B FIR - Brechot, Christian IR - Brechot C FIR - Delorme, Christine IR - Delorme C FIR - M'Rini, Christine IR - M'Rini C FIR - de Vos, Willem M IR - de Vos WM FIR - Maguin, Emmanuelle IR - Maguin E FIR - Varela, Encarna IR - Varela E FIR - Guedon, Eric IR - Guedon E FIR - Gwen, Falony IR - Gwen F FIR - Haimet, Florence IR - Haimet F FIR - Artiguenave, Francois IR - Artiguenave F FIR - Vandemeulebrouck, Gaetana IR - Vandemeulebrouck G FIR - Denariaz, Gerard IR - Denariaz G FIR - Khaci, Ghalia IR - Khaci G FIR - Blottiere, Herve IR - Blottiere H FIR - Knol, Jan IR - Knol J FIR - Weissenbach, Jean IR - Weissenbach J FIR - van Hylckama Vlieg, Johan E T IR - van Hylckama Vlieg JE FIR - Torben, Jorgensen IR - Torben J FIR - Parkhill, Julian IR - Parkhill J FIR - Turner, Keith IR - Turner K FIR - van de Guchte, Maarten IR - van de Guchte M FIR - Antolin, Maria IR - Antolin M FIR - Rescigno, Maria IR - Rescigno M FIR - Kleerebezem, Michiel IR - Kleerebezem M FIR - Derrien, Muriel IR - Derrien M FIR - Galleron, Nathalie IR - Galleron N FIR - Sanchez, Nicolas IR - Sanchez N FIR - Grarup, Niels IR - Grarup N FIR - Veiga, Patrick IR - Veiga P FIR - Oozeer, Raish IR - Oozeer R FIR - Dervyn, Rozenn IR - Dervyn R FIR - Layec, Severine IR - Layec S FIR - Bruls, Thomas IR - Bruls T FIR - Winogradski, Yohanan IR - Winogradski Y FIR - Erwin G, Zoetendal IR - Erwin G Z EDAT- 2014/07/07 06:00 MHDA- 2015/04/14 06:00 CRDT- 2014/07/07 06:00 PHST- 2014/02/12 00:00 [received] PHST- 2014/05/22 00:00 [accepted] PHST- 2014/07/07 06:00 [entrez] PHST- 2014/07/07 06:00 [pubmed] PHST- 2015/04/14 06:00 [medline] AID - nbt.2939 [pii] AID - 10.1038/nbt.2939 [doi] PST - ppublish SO - Nat Biotechnol. 2014 Aug;32(8):822-8. doi: 10.1038/nbt.2939. Epub 2014 Jul 6.