Genome-wide analysis of tomato long non-coding RNAs and identification as endogenous target mimic for microRNA in response to TYLCV infection

Recently, a large number of long noncoding RNAs (lncRNAs) have emerged as important regulators of many biological processes in animals and plants. However, how lncRNAs function during plant DNA virus infection is largely unknown. We performed strand-specific paired-end RNA sequencing of tomato sampl...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Scientific reports 2015-12, Vol.5 (1), p.16946-16946, Article 16946
Hauptverfasser: Wang, Jinyan, Yu, Wengui, Yang, Yuwen, Li, Xiao, Chen, Tianzi, Liu, Tingli, Ma, Na, Yang, Xu, Liu, Renyi, Zhang, Baolong
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 16946
container_issue 1
container_start_page 16946
container_title Scientific reports
container_volume 5
creator Wang, Jinyan
Yu, Wengui
Yang, Yuwen
Li, Xiao
Chen, Tianzi
Liu, Tingli
Ma, Na
Yang, Xu
Liu, Renyi
Zhang, Baolong
description Recently, a large number of long noncoding RNAs (lncRNAs) have emerged as important regulators of many biological processes in animals and plants. However, how lncRNAs function during plant DNA virus infection is largely unknown. We performed strand-specific paired-end RNA sequencing of tomato samples infected with Tomato yellow leaf curl virus (TYLCV) with three biological replicates. Overall, we predicted 1565 lncRNAs including long intergenic ncRNAs (lincRNAs) and natural antisense transcripts (lncNATs) and definitively identified lnRNAs that are involved in TYLCV infection by virus-induced gene silencing (VIGS). We also verified the functions of a set of lncRNAs that were differentially expressed between 0 and 7 days post inoculation (dpi). More importantly, we found that several lncRNAs acted as competing endogenous target mimics (eTMs) for tomato microRNAs involved in the TYLCV infection. These results provide new insight into lncRNAs involved in the response to TYLCV infection that are important components of the TYLCV network in tomatoes.
doi_str_mv 10.1038/srep16946
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4683531</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4103259111</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-431fd1b5d4a2b8bf2218033a4781ff6085116e6ce2138006b80cf2f755aec92d3</originalsourceid><addsrcrecordid>eNplkd9qFTEQxoMottRe-AIS8EaFtfm_2RuhHGoVDhakCl6FbDZZU3aTY7LH0ofwnZ1y6uGouckw88s3k_kQek7JW0q4PqvFb6jqhHqEjhkRsmGcsccH8RE6rfWGwJGsE7R7io6YUm2nOnKMfl36lGff3MbBY5vsdFdjxTngJc92yXjKacQpp8blIUL4-dN5BW7AwKclhujsEnPCtmKfhjyC2rbixZbRL3iOc3Q45AKRKxne4phw8XWTU_XQAl9_W6--QjJ4dy_zDD0Jdqr-9OE-QV_eX1yvPjTrq8uPq_N14wTXSyM4DQPt5SAs63UfGKOacG5Fq2kIimhJqfLKeUa5JkT1mrjAQiul9a5jAz9B73a6m20_-8HBV4qdzKbE2ZY7k200f1dS_G7G_NMIpbnkFARePQiU_GPr62LmWJ2fJps8LMDQVhIhCOMc0Jf_oDd5W2DTQMFwlEqhWqBe7yjYUwVLw34YSsy9z2bvM7AvDqffk39cBeDNDqhQSqMvBy3_U_sNslazNQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1800115467</pqid></control><display><type>article</type><title>Genome-wide analysis of tomato long non-coding RNAs and identification as endogenous target mimic for microRNA in response to TYLCV infection</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature OA Free Journals</source><creator>Wang, Jinyan ; Yu, Wengui ; Yang, Yuwen ; Li, Xiao ; Chen, Tianzi ; Liu, Tingli ; Ma, Na ; Yang, Xu ; Liu, Renyi ; Zhang, Baolong</creator><creatorcontrib>Wang, Jinyan ; Yu, Wengui ; Yang, Yuwen ; Li, Xiao ; Chen, Tianzi ; Liu, Tingli ; Ma, Na ; Yang, Xu ; Liu, Renyi ; Zhang, Baolong</creatorcontrib><description>Recently, a large number of long noncoding RNAs (lncRNAs) have emerged as important regulators of many biological processes in animals and plants. However, how lncRNAs function during plant DNA virus infection is largely unknown. We performed strand-specific paired-end RNA sequencing of tomato samples infected with Tomato yellow leaf curl virus (TYLCV) with three biological replicates. Overall, we predicted 1565 lncRNAs including long intergenic ncRNAs (lincRNAs) and natural antisense transcripts (lncNATs) and definitively identified lnRNAs that are involved in TYLCV infection by virus-induced gene silencing (VIGS). We also verified the functions of a set of lncRNAs that were differentially expressed between 0 and 7 days post inoculation (dpi). More importantly, we found that several lncRNAs acted as competing endogenous target mimics (eTMs) for tomato microRNAs involved in the TYLCV infection. These results provide new insight into lncRNAs involved in the response to TYLCV infection that are important components of the TYLCV network in tomatoes.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep16946</identifier><identifier>PMID: 26679690</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/449 ; 631/449/1659 ; 631/449/2661/2666 ; Antisense RNA ; Base Sequence ; Begomovirus - physiology ; Deoxyribonucleic acid ; DNA ; DNA sequencing ; Gene Expression Regulation, Plant ; Gene Silencing ; Genome, Plant ; Genomes ; Humanities and Social Sciences ; Infections ; Inoculation ; MicroRNAs - antagonists &amp; inhibitors ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; multidisciplinary ; Oligonucleotides, Antisense - metabolism ; Plant diseases ; Plant Diseases - virology ; Plant viruses ; Real-Time Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - metabolism ; Science ; Sequence Alignment ; Sequence Analysis, RNA ; Solanum lycopersicum - genetics ; Solanum lycopersicum - growth &amp; development ; Tomatoes ; Yellow leaf</subject><ispartof>Scientific reports, 2015-12, Vol.5 (1), p.16946-16946, Article 16946</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Dec 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-431fd1b5d4a2b8bf2218033a4781ff6085116e6ce2138006b80cf2f755aec92d3</citedby><cites>FETCH-LOGICAL-c438t-431fd1b5d4a2b8bf2218033a4781ff6085116e6ce2138006b80cf2f755aec92d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683531/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683531/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26679690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jinyan</creatorcontrib><creatorcontrib>Yu, Wengui</creatorcontrib><creatorcontrib>Yang, Yuwen</creatorcontrib><creatorcontrib>Li, Xiao</creatorcontrib><creatorcontrib>Chen, Tianzi</creatorcontrib><creatorcontrib>Liu, Tingli</creatorcontrib><creatorcontrib>Ma, Na</creatorcontrib><creatorcontrib>Yang, Xu</creatorcontrib><creatorcontrib>Liu, Renyi</creatorcontrib><creatorcontrib>Zhang, Baolong</creatorcontrib><title>Genome-wide analysis of tomato long non-coding RNAs and identification as endogenous target mimic for microRNA in response to TYLCV infection</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Recently, a large number of long noncoding RNAs (lncRNAs) have emerged as important regulators of many biological processes in animals and plants. However, how lncRNAs function during plant DNA virus infection is largely unknown. We performed strand-specific paired-end RNA sequencing of tomato samples infected with Tomato yellow leaf curl virus (TYLCV) with three biological replicates. Overall, we predicted 1565 lncRNAs including long intergenic ncRNAs (lincRNAs) and natural antisense transcripts (lncNATs) and definitively identified lnRNAs that are involved in TYLCV infection by virus-induced gene silencing (VIGS). We also verified the functions of a set of lncRNAs that were differentially expressed between 0 and 7 days post inoculation (dpi). More importantly, we found that several lncRNAs acted as competing endogenous target mimics (eTMs) for tomato microRNAs involved in the TYLCV infection. These results provide new insight into lncRNAs involved in the response to TYLCV infection that are important components of the TYLCV network in tomatoes.</description><subject>631/449</subject><subject>631/449/1659</subject><subject>631/449/2661/2666</subject><subject>Antisense RNA</subject><subject>Base Sequence</subject><subject>Begomovirus - physiology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>Gene Expression Regulation, Plant</subject><subject>Gene Silencing</subject><subject>Genome, Plant</subject><subject>Genomes</subject><subject>Humanities and Social Sciences</subject><subject>Infections</subject><subject>Inoculation</subject><subject>MicroRNAs - antagonists &amp; inhibitors</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>multidisciplinary</subject><subject>Oligonucleotides, Antisense - metabolism</subject><subject>Plant diseases</subject><subject>Plant Diseases - virology</subject><subject>Plant viruses</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Science</subject><subject>Sequence Alignment</subject><subject>Sequence Analysis, RNA</subject><subject>Solanum lycopersicum - genetics</subject><subject>Solanum lycopersicum - growth &amp; development</subject><subject>Tomatoes</subject><subject>Yellow leaf</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkd9qFTEQxoMottRe-AIS8EaFtfm_2RuhHGoVDhakCl6FbDZZU3aTY7LH0ofwnZ1y6uGouckw88s3k_kQek7JW0q4PqvFb6jqhHqEjhkRsmGcsccH8RE6rfWGwJGsE7R7io6YUm2nOnKMfl36lGff3MbBY5vsdFdjxTngJc92yXjKacQpp8blIUL4-dN5BW7AwKclhujsEnPCtmKfhjyC2rbixZbRL3iOc3Q45AKRKxne4phw8XWTU_XQAl9_W6--QjJ4dy_zDD0Jdqr-9OE-QV_eX1yvPjTrq8uPq_N14wTXSyM4DQPt5SAs63UfGKOacG5Fq2kIimhJqfLKeUa5JkT1mrjAQiul9a5jAz9B73a6m20_-8HBV4qdzKbE2ZY7k200f1dS_G7G_NMIpbnkFARePQiU_GPr62LmWJ2fJps8LMDQVhIhCOMc0Jf_oDd5W2DTQMFwlEqhWqBe7yjYUwVLw34YSsy9z2bvM7AvDqffk39cBeDNDqhQSqMvBy3_U_sNslazNQ</recordid><startdate>20151218</startdate><enddate>20151218</enddate><creator>Wang, Jinyan</creator><creator>Yu, Wengui</creator><creator>Yang, Yuwen</creator><creator>Li, Xiao</creator><creator>Chen, Tianzi</creator><creator>Liu, Tingli</creator><creator>Ma, Na</creator><creator>Yang, Xu</creator><creator>Liu, Renyi</creator><creator>Zhang, Baolong</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151218</creationdate><title>Genome-wide analysis of tomato long non-coding RNAs and identification as endogenous target mimic for microRNA in response to TYLCV infection</title><author>Wang, Jinyan ; Yu, Wengui ; Yang, Yuwen ; Li, Xiao ; Chen, Tianzi ; Liu, Tingli ; Ma, Na ; Yang, Xu ; Liu, Renyi ; Zhang, Baolong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-431fd1b5d4a2b8bf2218033a4781ff6085116e6ce2138006b80cf2f755aec92d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>631/449</topic><topic>631/449/1659</topic><topic>631/449/2661/2666</topic><topic>Antisense RNA</topic><topic>Base Sequence</topic><topic>Begomovirus - physiology</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA sequencing</topic><topic>Gene Expression Regulation, Plant</topic><topic>Gene Silencing</topic><topic>Genome, Plant</topic><topic>Genomes</topic><topic>Humanities and Social Sciences</topic><topic>Infections</topic><topic>Inoculation</topic><topic>MicroRNAs - antagonists &amp; inhibitors</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>multidisciplinary</topic><topic>Oligonucleotides, Antisense - metabolism</topic><topic>Plant diseases</topic><topic>Plant Diseases - virology</topic><topic>Plant viruses</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>Science</topic><topic>Sequence Alignment</topic><topic>Sequence Analysis, RNA</topic><topic>Solanum lycopersicum - genetics</topic><topic>Solanum lycopersicum - growth &amp; development</topic><topic>Tomatoes</topic><topic>Yellow leaf</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jinyan</creatorcontrib><creatorcontrib>Yu, Wengui</creatorcontrib><creatorcontrib>Yang, Yuwen</creatorcontrib><creatorcontrib>Li, Xiao</creatorcontrib><creatorcontrib>Chen, Tianzi</creatorcontrib><creatorcontrib>Liu, Tingli</creatorcontrib><creatorcontrib>Ma, Na</creatorcontrib><creatorcontrib>Yang, Xu</creatorcontrib><creatorcontrib>Liu, Renyi</creatorcontrib><creatorcontrib>Zhang, Baolong</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jinyan</au><au>Yu, Wengui</au><au>Yang, Yuwen</au><au>Li, Xiao</au><au>Chen, Tianzi</au><au>Liu, Tingli</au><au>Ma, Na</au><au>Yang, Xu</au><au>Liu, Renyi</au><au>Zhang, Baolong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide analysis of tomato long non-coding RNAs and identification as endogenous target mimic for microRNA in response to TYLCV infection</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-12-18</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>16946</spage><epage>16946</epage><pages>16946-16946</pages><artnum>16946</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Recently, a large number of long noncoding RNAs (lncRNAs) have emerged as important regulators of many biological processes in animals and plants. However, how lncRNAs function during plant DNA virus infection is largely unknown. We performed strand-specific paired-end RNA sequencing of tomato samples infected with Tomato yellow leaf curl virus (TYLCV) with three biological replicates. Overall, we predicted 1565 lncRNAs including long intergenic ncRNAs (lincRNAs) and natural antisense transcripts (lncNATs) and definitively identified lnRNAs that are involved in TYLCV infection by virus-induced gene silencing (VIGS). We also verified the functions of a set of lncRNAs that were differentially expressed between 0 and 7 days post inoculation (dpi). More importantly, we found that several lncRNAs acted as competing endogenous target mimics (eTMs) for tomato microRNAs involved in the TYLCV infection. These results provide new insight into lncRNAs involved in the response to TYLCV infection that are important components of the TYLCV network in tomatoes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26679690</pmid><doi>10.1038/srep16946</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2045-2322
ispartof Scientific reports, 2015-12, Vol.5 (1), p.16946-16946, Article 16946
issn 2045-2322
2045-2322
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4683531
source MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals
subjects 631/449
631/449/1659
631/449/2661/2666
Antisense RNA
Base Sequence
Begomovirus - physiology
Deoxyribonucleic acid
DNA
DNA sequencing
Gene Expression Regulation, Plant
Gene Silencing
Genome, Plant
Genomes
Humanities and Social Sciences
Infections
Inoculation
MicroRNAs - antagonists & inhibitors
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
multidisciplinary
Oligonucleotides, Antisense - metabolism
Plant diseases
Plant Diseases - virology
Plant viruses
Real-Time Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA, Long Noncoding - metabolism
Science
Sequence Alignment
Sequence Analysis, RNA
Solanum lycopersicum - genetics
Solanum lycopersicum - growth & development
Tomatoes
Yellow leaf
title Genome-wide analysis of tomato long non-coding RNAs and identification as endogenous target mimic for microRNA in response to TYLCV infection
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T02%3A48%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-wide%20analysis%20of%20tomato%20long%20non-coding%20RNAs%20and%20identification%20as%20endogenous%20target%20mimic%20for%20microRNA%20in%20response%20to%20TYLCV%20infection&rft.jtitle=Scientific%20reports&rft.au=Wang,%20Jinyan&rft.date=2015-12-18&rft.volume=5&rft.issue=1&rft.spage=16946&rft.epage=16946&rft.pages=16946-16946&rft.artnum=16946&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep16946&rft_dat=%3Cproquest_pubme%3E4103259111%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1800115467&rft_id=info:pmid/26679690&rfr_iscdi=true