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Binning metagenomic contigs by coverage and composition
KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-2467-008X
KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Bioinformatics Infrastructure for Life Sciences (BILS), Sweden.
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2014 (English)In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 11, no 11, p. 1144-1146Article in journal (Refereed) Published
Abstract [en]

Shotgun sequencing enables the reconstruction of genomes from complex microbial communities, but because assembly does not reconstruct entire genomes, it is necessary to bin genome fragments. Here we present CONCOCT, a new algorithm that combines sequence composition and coverage across multiple samples, to automatically cluster contigs into genomes. We demonstrate high recall and precision on artificial as well as real human gut metagenome data sets.

Place, publisher, year, edition, pages
2014. Vol. 11, no 11, p. 1144-1146
Keywords [en]
Sequences, Genomes
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-157613DOI: 10.1038/NMETH.3103ISI: 000344580600021PubMedID: 25218180Scopus ID: 2-s2.0-84908597294OAI: oai:DiVA.org:kth-157613DiVA, id: diva2:771118
Funder
Swedish Research Council, 2011-5689Formas, 2009-1174Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20141212

Available from: 2014-12-12 Created: 2014-12-11 Last updated: 2018-05-15Bibliographically approved
In thesis
1. Bioinformatic Methods in Metagenomics
Open this publication in new window or tab >>Bioinformatic Methods in Metagenomics
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Microbial organisms are a vital part of our global ecosystem. Yet, our knowledge of them is still lacking. Direct sequencing of microbial communities, i.e. metagenomics, have enabled detailed studies of these microscopic organisms by inspection of their DNA sequences without the need to culture them. Furthermore, the development of modern high- throughput sequencing technologies have made this approach more powerful and cost-effective. Taken together, this has shifted the field of microbiology from previously being centered around microscopy and culturing studies, to largely consist of computational analyses of DNA sequences. One such computational analysis which is the main focus of this thesis, aims at reconstruction of the complete DNA sequence of an organism, i.e. its genome, directly from short metagenomic sequences.

This thesis consists of an introduction to the subject followed by five papers. Paper I describes a large metagenomic data resource spanning the Baltic Sea microbial communities. This dataset is complemented with a web-interface allowing researchers to easily extract and visualize detailed information. Paper II introduces a bioinformatic method which is able to reconstruct genomes from metagenomic data. This method, which is termed CONCOCT, is applied on Baltic Sea metagenomics data in Paper III and Paper V. This enabled the reconstruction of a large number of genomes. Analysis of these genomes in Paper III led to the proposal of, and evidence for, a global brackish microbiome. Paper IV presents a comparison between genomes reconstructed from metagenomes with single-cell sequenced genomes. This further validated the technique presented in Paper II as it was found to produce larger and more complete genomes than single-cell sequencing.

Abstract [sv]

Mikrobiella organismer är en vital del av vårt globala ekosystem. Trots detta är vår kunskap om dessa fortfarande begränsad. Sekvensering direkt applicerad på mikrobiella samhällen, så kallad metagenomik, har möjliggjort detaljerade studier av dessa mikroskopiska organismer genom deras DNA-sekvenser. Utvecklingen av modern sekvenseringsteknik har vidare gjort denna strategi både mer kraftfull och mer kostnadseffektiv. Sammantaget har detta förändrat mikrobiologi-fältet, från att ha varit centrerat kring mikroskopi, till att till stor del bero på dataintensiva analyser av DNA-sekvenser. En sådan analys, som är det huvudsakliga fokuset för den här avhandlingen, syftar till att återskapa den kompletta DNA-sekvensen för en organism, dvs. dess genom, direkt från korta metagenom-sekvenser.

Den här avhandlingen består av en introduktion till ämnet, följt av fem artiklar. Artikel I beskriver en omfattande databas för metagenomik över Östersjöns mikrobiella samhällen. Till denna databas hör också en webbsida som ger forskare möjlighet att lätt extrahera och visualisera detaljerad information. Artikel II introducerar en bioinformatisk metod som kan återskapa genom från metagenom. Denna metod, som kallas CONCOCT, används för data från Östersjön i artikel III och Artikel V. Detta möjliggjorde återskapandet av ett stort antal genom. Analys av dessa genom presenterad i Artikel III ledde till hypotesen om, och belägg för, ett globalt brackvattenmikrobiom. Artikel IV innehåller en jämförelse mellan genom återskapade från metagenom och individuellt sekvenserade genom. Detta validerade metoden som presenterades i Artikel II ytterligare då denna metod visade sig producera större och mer kompletta genom än sekvensering av individuella celler.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2018. p. 51
Series
TRITA-CBH-FOU ; 2018:25
Keywords
Bioinformatics, Metagenomics, Microbiome, Binning, Baltic Sea, Bioinformatik, Metagenomik, Mikrobiom, Binning, Östersjön
National Category
Bioinformatics and Systems Biology Bioinformatics (Computational Biology) Microbiology
Identifiers
urn:nbn:se:kth:diva-227965 (URN)978-91-7729-799-4 (ISBN)
Public defence
2018-06-08, Air and Fire, Science for Life Laboratory, Tomtebodavägen 23, Solna, 10:00 (English)
Opponent
Supervisors
Funder
BONUS - Science for a better future of the Baltic Sea region, Art 185
Note

QC 20180516

Available from: 2018-05-16 Created: 2018-05-15 Last updated: 2018-05-16Bibliographically approved

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