A Profile Hidden Markov Model to investigate the distribution and frequency of LanB-encoding lantibiotic modification genes in the human oral and gut microbiome

dc.contributor.authorWalsh, Calum J.
dc.contributor.authorGuinane, Caitriona M.
dc.contributor.authorO'Toole, Paul W.
dc.contributor.authorCotter, Paul D.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2017-05-11T10:57:12Z
dc.date.available2017-05-11T10:57:12Z
dc.date.issued2017-04-27
dc.date.updated2017-05-11T10:43:21Z
dc.description.abstractBackground: The human microbiota plays a key role in health and disease, and bacteriocins, which are small, bacterially produced, antimicrobial peptides, are likely to have an important function in the stability and dynamics of this community. Here we examined the density and distribution of the subclass I lantibiotic modification protein, LanB, in human oral and stool microbiome datasets using a specially constructed profile Hidden Markov Model (HMM). Methods: The model was validated by correctly identifying known lanB genes in the genomes of known bacteriocin producers more effectively than other methods, while being sensitive enough to differentiate between different subclasses of lantibiotic modification proteins. This approach was compared with two existing methods to screen both genomic and metagenomic datasets obtained from the Human Microbiome Project (HMP). Results: Of the methods evaluated, the new profile HMM identified the greatest number of putative LanB proteins in the stool and oral metagenome data while BlastP identified the fewest. In addition, the model identified more LanB proteins than a pre-existing Pfam lanthionine dehydratase model. Searching the gastrointestinal tract subset of the HMP reference genome database with the new HMM identified seven putative subclass I lantibiotic producers, including two members of the Coprobacillus genus. Conclusions: These findings establish custom profile HMMs as a potentially powerful tool in the search for novel bioactive producers with the power to benefit human health, and reinforce the repertoire of apparent bacteriocin-encoding gene clusters that may have been overlooked by culture-dependent mining efforts to date.en
dc.description.sponsorshipScience Foundation Ireland (SFI Grant Number 11/PI/1137)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide3254
dc.identifier.citationWalsh, C. J., Guinane, C. M., O’Toole, P.W. and Cotter, P. D. (2017) ‘A Profile Hidden Markov Model to investigate the distribution and frequency of LanB-encoding lantibiotic modification genes in the human oral and gut microbiome’, PeerJ, 5:e3254 (19 pp). doi:10.7717/peerj.3254en
dc.identifier.doi10.7717/peerj.3254
dc.identifier.endpage19en
dc.identifier.issn2167-8359
dc.identifier.journaltitlePeerJen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/3943
dc.identifier.volume5en
dc.language.isoenen
dc.publisherPeerJen
dc.rights© 2017, Walsh et al. Distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectHidden Markov Modelen
dc.subjectLantibioticen
dc.subjectBacteriocinen
dc.subjectMetagenomicen
dc.subjectMicrobiotaen
dc.titleA Profile Hidden Markov Model to investigate the distribution and frequency of LanB-encoding lantibiotic modification genes in the human oral and gut microbiomeen
dc.typeArticle (peer-reviewed)en
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