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dc.contributor.author
Zagordi, Osvaldo
dc.contributor.author
Klein, Rolf
dc.contributor.author
Däumer, Martin
dc.contributor.author
Beerenwinkel, Niko
dc.date.accessioned
2019-04-02T10:29:10Z
dc.date.available
2017-06-09T08:22:46Z
dc.date.available
2019-04-02T10:29:10Z
dc.date.issued
2010-11
dc.identifier.other
10.1093/nar/gkq655
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/27232
dc.identifier.doi
10.3929/ethz-b-000027232
dc.description.abstract
Next-generation sequencing technologies can be used to analyse genetically heterogeneous samples at unprecedented detail. The high coverage achievable with these methods enables the detection of many low-frequency variants. However, sequencing errors complicate the analysis of mixed populations and result in inflated estimates of genetic diversity. We developed a probabilistic Bayesian approach to minimize the effect of errors on the detection of minority variants. We applied it to pyrosequencing data obtained from a 1.5‐kb-fragment of the HIV-1 gag/pol gene in two control and two clinical samples. The effect of PCR amplification was analysed. Error correction resulted in a two- and five-fold decrease of the pyrosequencing base substitution rate, from 0.05% to 0.03% and from 0.25% to 0.05% in the non-PCR and PCR-amplified samples, respectively. We were able to detect viral clones as rare as 0.1% with perfect sequence reconstruction. Probabilistic haplotype inference outperforms the counting-based calling method in both precision and recall. Genetic diversity observed within and between two clinical samples resulted in various patterns of phenotypic drug resistance and suggests a close epidemiological link. We conclude that pyrosequencing can be used to investigate genetically diverse samples with high accuracy if technical errors are properly treated.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Oxford University Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/2.5/
dc.title
Error correction of next-generation sequencing data and reliable estimation of HIV quasispecies
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 2.5 Generic
dc.date.published
2010-07-29
ethz.journal.title
Nucleic acids research
ethz.journal.volume
38
en_US
ethz.journal.issue
21
en_US
ethz.pages.start
7400
en_US
ethz.pages.end
7409
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
000038633
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03790 - Beerenwinkel, Niko / Beerenwinkel, Niko
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03790 - Beerenwinkel, Niko / Beerenwinkel, Niko
ethz.date.deposited
2017-06-09T08:22:54Z
ethz.source
ECIT
ethz.identifier.importid
imp59364d75c577327363
ethz.ecitpid
pub:46025
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-18T08:31:26Z
ethz.rosetta.lastUpdated
2019-04-02T10:29:38Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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