Identification and Typing of Human Enterovirus: A Genomic Barcode Approach
Identifieur interne : 001064 ( Pmc/Corpus ); précédent : 001063; suivant : 001065Identification and Typing of Human Enterovirus: A Genomic Barcode Approach
Auteurs : Chengguo Wei ; Guoqing Wang ; Xin Chen ; Honglan Huang ; Bin Liu ; Ying Xu ; Fan LiSource :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
Identification and typing of human enterovirus (HEVs) are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-
Url:
DOI: 10.1371/journal.pone.0026296
PubMed: 22022592
PubMed Central: 3194813
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PMC:3194813Le document en format XML
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<author><name sortKey="Wang, Guoqing" sort="Wang, Guoqing" uniqKey="Wang G" first="Guoqing" last="Wang">Guoqing Wang</name>
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<author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name>
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<author><name sortKey="Liu, Bin" sort="Liu, Bin" uniqKey="Liu B" first="Bin" last="Liu">Bin Liu</name>
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<author><name sortKey="Xu, Ying" sort="Xu, Ying" uniqKey="Xu Y" first="Ying" last="Xu">Ying Xu</name>
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<author><name sortKey="Li, Fan" sort="Li, Fan" uniqKey="Li F" first="Fan" last="Li">Fan Li</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification and Typing of Human Enterovirus: A Genomic Barcode Approach</title>
<author><name sortKey="Wei, Chengguo" sort="Wei, Chengguo" uniqKey="Wei C" first="Chengguo" last="Wei">Chengguo Wei</name>
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<author><name sortKey="Wang, Guoqing" sort="Wang, Guoqing" uniqKey="Wang G" first="Guoqing" last="Wang">Guoqing Wang</name>
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<author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name>
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<author><name sortKey="Huang, Honglan" sort="Huang, Honglan" uniqKey="Huang H" first="Honglan" last="Huang">Honglan Huang</name>
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<author><name sortKey="Liu, Bin" sort="Liu, Bin" uniqKey="Liu B" first="Bin" last="Liu">Bin Liu</name>
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<author><name sortKey="Xu, Ying" sort="Xu, Ying" uniqKey="Xu Y" first="Ying" last="Xu">Ying Xu</name>
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<affiliation><nlm:aff id="aff3"><addr-line>College of Computer Science and Technology, Jilin University, Changchun, Jilin, China</addr-line>
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<author><name sortKey="Li, Fan" sort="Li, Fan" uniqKey="Li F" first="Fan" last="Li">Fan Li</name>
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<front><div type="abstract" xml:lang="en"><p>Identification and typing of human enterovirus (HEVs) are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-<italic>mer</italic>
based barcode image for each genome, HEV or other human viruses, for a fixed k, 1<italic>mer</italic>
frequency distribution across the whole genome for all combinations of k-<italic>mers</italic>
. A phylogenetic tree is constructed using a barcode-based distance and a neighbor-joining method among a set of 443 representative non-HEV human viruses and 395 HEV sequences. The tree shows a clear separation of the HEV viruses from all the non-HEV viruses with 100% accuracy and a separation of the HEVs into four distinct clads with 93.4% consistency with a multiple sequence alignment-based phylogeny. Our detailed analyses of the HEVs having different typing results by the two methods indicate that our results are in better agreement with known information about the HEVs.</p>
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<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
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<article-meta><article-id pub-id-type="pmid">22022592</article-id>
<article-id pub-id-type="pmc">3194813</article-id>
<article-id pub-id-type="publisher-id">PONE-D-11-10269</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0026296</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Biology</subject>
<subj-group><subject>Genomics</subject>
<subj-group><subject>Comparative Genomics</subject>
<subject>Genome Analysis Tools</subject>
<subject>Genome Expression Analysis</subject>
<subject>Genome Sequencing</subject>
</subj-group>
</subj-group>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Virology</subject>
<subj-group><subject>Viral classification</subject>
<subj-group><subject>RNA viruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject>
<subj-group><subject>Infectious Diseases</subject>
<subj-group><subject>Viral Diseases</subject>
<subj-group><subject>Enterovirus Infection</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Identification and Typing of Human Enterovirus: A Genomic Barcode Approach</article-title>
<alt-title alt-title-type="running-head">Typing of Human Enterovirus</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Wei</surname>
<given-names>Chengguo</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Wang</surname>
<given-names>Guoqing</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Xin</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Huang</surname>
<given-names>Honglan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Bin</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xu</surname>
<given-names>Ying</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Fan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Department of Pathogeny Biology, Norman Bethune Medical College of Jilin University, Changchun, Jilin, China</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology, and Institute of Bioinformatics, University of Georgia, Athens, Georgia, United States of America</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>College of Computer Science and Technology, Jilin University, Changchun, Jilin, China</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>The First Bethune Hospital of Jilin University, Changchun, Jilin, China</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Norris</surname>
<given-names>Philip J.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Blood Systems Research Institute, United States of America</aff>
<author-notes><corresp id="cor1">* E-mail: <email>xyn@bmb.uga.edu</email>
(YX); <email>lifan@jlu.edu.cn</email>
(FL)</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: CW GW. Performed the experiments: CW XC HH. Analyzed the data: XC BL. Contributed reagents/materials/analysis tools: XC CW GW BL. Wrote the paper: CW. Designed the study: FL YX.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>14</day>
<month>10</month>
<year>2011</year>
</pub-date>
<volume>6</volume>
<issue>10</issue>
<elocation-id>e26296</elocation-id>
<history><date date-type="received"><day>7</day>
<month>6</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>23</day>
<month>9</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Wei et al.</copyright-statement>
<copyright-year>2011</copyright-year>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<abstract><p>Identification and typing of human enterovirus (HEVs) are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-<italic>mer</italic>
based barcode image for each genome, HEV or other human viruses, for a fixed k, 1<italic>mer</italic>
frequency distribution across the whole genome for all combinations of k-<italic>mers</italic>
. A phylogenetic tree is constructed using a barcode-based distance and a neighbor-joining method among a set of 443 representative non-HEV human viruses and 395 HEV sequences. The tree shows a clear separation of the HEV viruses from all the non-HEV viruses with 100% accuracy and a separation of the HEVs into four distinct clads with 93.4% consistency with a multiple sequence alignment-based phylogeny. Our detailed analyses of the HEVs having different typing results by the two methods indicate that our results are in better agreement with known information about the HEVs.</p>
</abstract>
<counts><page-count count="5"></page-count>
</counts>
</article-meta>
</front>
<body><sec id="s1"><title>Introduction</title>
<p>Human enterovirus (HEVs) are a genus of (+)ssRNA viruses, and they are among the most common human viruses, causing a wide range of acute diseases, such as upper respiratory tract infection, febrile rash, encephalitis, acute flaccid paralysis <xref rid="pone.0026296-Palacios1" ref-type="bibr">[1]</xref>
and severe chronic disorders <xref rid="pone.0026296-Kearney1" ref-type="bibr">[2]</xref>
, <xref rid="pone.0026296-Kim1" ref-type="bibr">[3]</xref>
, <xref rid="pone.0026296-Hober1" ref-type="bibr">[4]</xref>
, <xref rid="pone.0026296-Richer1" ref-type="bibr">[5]</xref>
. The prevalence and the clinical significance of HEVs are further manifested by multiple outbreaks of the hand, foot and mouth disease (HFMD) in Asia, mainly caused by enterovirus 71 <xref rid="pone.0026296-McMinn1" ref-type="bibr">[6]</xref>
, <xref rid="pone.0026296-Cardosa1" ref-type="bibr">[7]</xref>
, <xref rid="pone.0026296-Miyazawa1" ref-type="bibr">[8]</xref>
, <xref rid="pone.0026296-Zhang1" ref-type="bibr">[9]</xref>
. As of now, over 100 serotypes of the HEV have been documented <xref rid="pone.0026296-Oberste1" ref-type="bibr">[10]</xref>
, <xref rid="pone.0026296-Oberste2" ref-type="bibr">[11]</xref>
, <xref rid="pone.0026296-Norder1" ref-type="bibr">[12]</xref>
, <xref rid="pone.0026296-FauquetCMMayo1" ref-type="bibr">[13]</xref>
, and only a handful of them can cause severe diseases <xref rid="pone.0026296-Zhu1" ref-type="bibr">[14]</xref>
such as poliomyelitis by poliovirus <xref rid="pone.0026296-Heinsbroek1" ref-type="bibr">[15]</xref>
. It is known that 83.5% of the HEV-related disease cases were caused by 15 serotypes <xref rid="pone.0026296-Khetsuriani1" ref-type="bibr">[16]</xref>
. Therefore, classification of HEVs is important to designing novel diagnostic and treatment strategies.</p>
<p>A number of methods have been developed for classification (typing) of HEVs. The traditional method, based on biological properties of viruses such as antigenic differences <xref rid="pone.0026296-Grandien1" ref-type="bibr">[17]</xref>
, subdivided HEVs into poliovirus (PV), coxsackievirus (CV) groups A and B, echovirus, and the ‘new’ serotypes designated as EV-68 through EV-71 <xref rid="pone.0026296-Stanway1" ref-type="bibr">[18]</xref>
, <xref rid="pone.0026296-Nasri1" ref-type="bibr">[19]</xref>
, <xref rid="pone.0026296-Brown1" ref-type="bibr">[20]</xref>
. This method is expensive and time consuming, and could not handle some of the recently discovered HEV types such as some coxsackieviruses due to the lack of specific antisera <xref rid="pone.0026296-Kapsenberg1" ref-type="bibr">[21]</xref>
. Molecular techniques such as RT-PCR in conjunction with sequence alignment-based phylogeny reconstruction algorithms offer a sensitive and rapid alternative for the classification of HEVs. Based on a specific gene shared by the HEV genomes, this approach divides HEVs into four types: HEV-A through D <xref rid="pone.0026296-Pallansch1" ref-type="bibr">[22]</xref>
. However, this approach is not stable when tested using a different set of HEV genes, giving rise to a classification result (VP1 <xref rid="pone.0026296-Kottaridi1" ref-type="bibr">[23]</xref>
, <xref rid="pone.0026296-Oberste3" ref-type="bibr">[24]</xref>
, <xref rid="pone.0026296-Oberste4" ref-type="bibr">[25]</xref>
, VP2 <xref rid="pone.0026296-Nasri2" ref-type="bibr">[26]</xref>
, VP3 <xref rid="pone.0026296-Stadnick1" ref-type="bibr">[27]</xref>
, VP4 <xref rid="pone.0026296-Ishiko1" ref-type="bibr">[28]</xref>
), inconsistent with the first classification result. Phylogeny reconstruction based on the whole HEV genomes will not work easily since these genomes are not well conserved in multiple aspects including the gene orders and different levels of conservation for different sets of orthologous genes. And many genetic fragment, emerging with metagenome sequencing technique development, can not be classified using this sequence alignment method.</p>
<p>We present a novel classification method based on information derived from the whole genome sequences of HEVs instead of specific genes. To the best of our knowledge, there has not been any published research on virus typing using information derived from the whole genome sequences. Instead of appending all the gene sequences from the HEVs and then building a phylogeny based on such artificial sequences, which could be highly sensitive to weighting factors for different genes, we use information more intrinsic to individual HEV genomes to construct the phylogeny. Specifically we have used a barcode representation to represent each HEV genome <xref rid="pone.0026296-Zhou1" ref-type="bibr">[29]</xref>
. We have previously demonstrated that each organism has a unique barcode image; and more closely related genomes generally have more similar barcodes <xref rid="pone.0026296-Zhou1" ref-type="bibr">[29]</xref>
. This provides the basis for our barcode-based phylogeny analysis.</p>
<p>The basic idea of the genomic barcode is to represent a genome using a two-dimensional array with the row representing the genome axis contracted by N fold, the column representing the axis of all k-<italic>mers</italic>
for a fixed k (1<sup>th</sup>
k-<italic>mer</italic>
within the window from base-pair j*N + 1 to base-pair (j+1)*N, with N being the window size (the default values of the barcode program <xref rid="pone.0026296-Zhou1" ref-type="bibr">[29]</xref>
are k = 4 and N = 1,000 base-pairs (bps) but can be adjusted by the user). One very interesting property of any genomic barcode is that the frequency distribution for any k-<italic>mer</italic>
(for a fixed 1<italic>mer</italic>
although more sophisticated ways can be used to capture more information of the targeted barcodes <xref rid="pone.0026296-Zhou1" ref-type="bibr">[29]</xref>
.</p>