High-throughput sequencing reveals small RNAs involved in ASGV infection
Plant small RNAs (sRNAs) associated with virulent virus infections have been reported by previous studies, while the involvement of sRNAs in latent virus infection remains largely uncharacterised. Apple trees show a high degree of resistance and tolerance to viral infections. We analysed two sRNA de...
Gespeichert in:
| Veröffentlicht in: | BMC genomics 2014-07, Vol.15 (1), p.568-568, Article 568 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 568 |
|---|---|
| container_issue | 1 |
| container_start_page | 568 |
| container_title | BMC genomics |
| container_volume | 15 |
| creator | Visser, Marike Maree, Hans J Rees, D Jasper G Burger, Johan T |
| description | Plant small RNAs (sRNAs) associated with virulent virus infections have been reported by previous studies, while the involvement of sRNAs in latent virus infection remains largely uncharacterised. Apple trees show a high degree of resistance and tolerance to viral infections. We analysed two sRNA deep sequencing datasets, prepared from different RNA size fractions, to identify sRNAs involved in Apple stem grooving virus (ASGV) infection.
sRNA analysis revealed virus-derived siRNAs (vsiRNAs) originating from two ASGV genetic variants. A vsiRNA profile for one of the ASGV variants was also generated showing an increase in siRNA production towards the 3' end of the virus genome. Virus-derived sRNAs longer than those previously analysed were also observed in the sequencing data. Additionally, tRNA-derived sRNAs were identified and characterised. These sRNAs covered a broad size-range and originated from both ends of the mature tRNAs as well as from their central regions. Several tRNA-derived sRNAs showed differential regulation due to ASGV infection. No changes in microRNA, natural-antisense transcript siRNA, phased-siRNA and repeat-associated siRNA levels were observed.
This study is the first report on the apple sRNA-response to virus infection. The results revealed the vsiRNAs profile of an ASGV variant, as well as the alteration of the tRNA-derived sRNA profile in response to latent virus infection. It also highlights the importance of library preparation in the interpretation of high-throughput sequencing data. |
| doi_str_mv | 10.1186/1471-2164-15-568 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4118050</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A539565945</galeid><sourcerecordid>A539565945</sourcerecordid><originalsourceid>FETCH-LOGICAL-c558t-722d05b7b6a60b9e4a84ee1cf401504db58956775b30f3c89f0ac6fbfee088333</originalsourceid><addsrcrecordid>eNqNkk1v1DAQhiNERUvhzglF4lIOae34I84FaVVBt1LVSi1wtRxnnHWVxIudrODfM0vL0kUckA8zGj8zmnn1ZtkbSk4pVfKM8ooWJZW8oKIQUj3Ljnal50_yw-xlSveE0EqV4kV2WPK6Vlyoo2y59N2qmFYxzN1qPU95gm8zjNaPXR5hA6ZPeRpM3-e314uU-3ET-g20mOSLu4uvGB3YyYfxVXbgEIbXj_E4-_Lp4-fzZXF1c3F5vrgqrBBqKqqybIloqkYaSZoauFEcgFrHCRWEt41QtZBVJRpGHLOqdsRY6RoHQJRijB1nHx7mrudmgNbCOEXT63X0g4k_dDBe7_-MfqW7sNEcFSOC4ICTxwEx4Klp0oNPFvrejBDmpKkQvOYS1_kPlNeSccZLRN_9hd6HOY6oxC-KC1KV8g_VmR40ahdwRbsdqheC4eECSaRO_0Hha2HwNozgPNb3Gt7vNSAzwfepM3NK-vLudp8lD6yNIaUIbicdJXprKr11jd66BjfXaCpseftU8l3Dbxexnxb3xBM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1549450726</pqid></control><display><type>article</type><title>High-throughput sequencing reveals small RNAs involved in ASGV infection</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><creator>Visser, Marike ; Maree, Hans J ; Rees, D Jasper G ; Burger, Johan T</creator><creatorcontrib>Visser, Marike ; Maree, Hans J ; Rees, D Jasper G ; Burger, Johan T</creatorcontrib><description>Plant small RNAs (sRNAs) associated with virulent virus infections have been reported by previous studies, while the involvement of sRNAs in latent virus infection remains largely uncharacterised. Apple trees show a high degree of resistance and tolerance to viral infections. We analysed two sRNA deep sequencing datasets, prepared from different RNA size fractions, to identify sRNAs involved in Apple stem grooving virus (ASGV) infection.
sRNA analysis revealed virus-derived siRNAs (vsiRNAs) originating from two ASGV genetic variants. A vsiRNA profile for one of the ASGV variants was also generated showing an increase in siRNA production towards the 3' end of the virus genome. Virus-derived sRNAs longer than those previously analysed were also observed in the sequencing data. Additionally, tRNA-derived sRNAs were identified and characterised. These sRNAs covered a broad size-range and originated from both ends of the mature tRNAs as well as from their central regions. Several tRNA-derived sRNAs showed differential regulation due to ASGV infection. No changes in microRNA, natural-antisense transcript siRNA, phased-siRNA and repeat-associated siRNA levels were observed.
This study is the first report on the apple sRNA-response to virus infection. The results revealed the vsiRNAs profile of an ASGV variant, as well as the alteration of the tRNA-derived sRNA profile in response to latent virus infection. It also highlights the importance of library preparation in the interpretation of high-throughput sequencing data.</description><identifier>ISSN: 1471-2164</identifier><identifier>EISSN: 1471-2164</identifier><identifier>DOI: 10.1186/1471-2164-15-568</identifier><identifier>PMID: 24998458</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Apple stem grooving virus ; Base Sequence ; Disease Resistance - genetics ; Gene Expression Regulation, Plant ; Genetic aspects ; Genomes ; Genomics ; Health aspects ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Infections ; Malus ; Malus - genetics ; Malus - metabolism ; Malus - virology ; Medical research ; Medicine, Experimental ; Phylogeny ; Physiological aspects ; Plant Diseases - genetics ; Plant Diseases - virology ; Plant Viruses - physiology ; RNA, Plant - genetics ; RNA, Plant - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; RNA, Transfer - genetics ; RNA, Transfer - metabolism ; Sequence Analysis, RNA ; Studies ; Viral infections ; Virulence (Microbiology) ; Viruses</subject><ispartof>BMC genomics, 2014-07, Vol.15 (1), p.568-568, Article 568</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Visser et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Visser et al.; licensee BioMed Central Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-722d05b7b6a60b9e4a84ee1cf401504db58956775b30f3c89f0ac6fbfee088333</citedby><cites>FETCH-LOGICAL-c558t-722d05b7b6a60b9e4a84ee1cf401504db58956775b30f3c89f0ac6fbfee088333</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/PMC4118050/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118050/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24998458$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Visser, Marike</creatorcontrib><creatorcontrib>Maree, Hans J</creatorcontrib><creatorcontrib>Rees, D Jasper G</creatorcontrib><creatorcontrib>Burger, Johan T</creatorcontrib><title>High-throughput sequencing reveals small RNAs involved in ASGV infection</title><title>BMC genomics</title><addtitle>BMC Genomics</addtitle><description>Plant small RNAs (sRNAs) associated with virulent virus infections have been reported by previous studies, while the involvement of sRNAs in latent virus infection remains largely uncharacterised. Apple trees show a high degree of resistance and tolerance to viral infections. We analysed two sRNA deep sequencing datasets, prepared from different RNA size fractions, to identify sRNAs involved in Apple stem grooving virus (ASGV) infection.
sRNA analysis revealed virus-derived siRNAs (vsiRNAs) originating from two ASGV genetic variants. A vsiRNA profile for one of the ASGV variants was also generated showing an increase in siRNA production towards the 3' end of the virus genome. Virus-derived sRNAs longer than those previously analysed were also observed in the sequencing data. Additionally, tRNA-derived sRNAs were identified and characterised. These sRNAs covered a broad size-range and originated from both ends of the mature tRNAs as well as from their central regions. Several tRNA-derived sRNAs showed differential regulation due to ASGV infection. No changes in microRNA, natural-antisense transcript siRNA, phased-siRNA and repeat-associated siRNA levels were observed.
This study is the first report on the apple sRNA-response to virus infection. The results revealed the vsiRNAs profile of an ASGV variant, as well as the alteration of the tRNA-derived sRNA profile in response to latent virus infection. It also highlights the importance of library preparation in the interpretation of high-throughput sequencing data.</description><subject>Analysis</subject><subject>Apple stem grooving virus</subject><subject>Base Sequence</subject><subject>Disease Resistance - genetics</subject><subject>Gene Expression Regulation, Plant</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Host-Pathogen Interactions</subject><subject>Infections</subject><subject>Malus</subject><subject>Malus - genetics</subject><subject>Malus - metabolism</subject><subject>Malus - virology</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Phylogeny</subject><subject>Physiological aspects</subject><subject>Plant Diseases - genetics</subject><subject>Plant Diseases - virology</subject><subject>Plant Viruses - physiology</subject><subject>RNA, Plant - genetics</subject><subject>RNA, Plant - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>RNA, Transfer - genetics</subject><subject>RNA, Transfer - metabolism</subject><subject>Sequence Analysis, RNA</subject><subject>Studies</subject><subject>Viral infections</subject><subject>Virulence (Microbiology)</subject><subject>Viruses</subject><issn>1471-2164</issn><issn>1471-2164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkk1v1DAQhiNERUvhzglF4lIOae34I84FaVVBt1LVSi1wtRxnnHWVxIudrODfM0vL0kUckA8zGj8zmnn1ZtkbSk4pVfKM8ooWJZW8oKIQUj3Ljnal50_yw-xlSveE0EqV4kV2WPK6Vlyoo2y59N2qmFYxzN1qPU95gm8zjNaPXR5hA6ZPeRpM3-e314uU-3ET-g20mOSLu4uvGB3YyYfxVXbgEIbXj_E4-_Lp4-fzZXF1c3F5vrgqrBBqKqqybIloqkYaSZoauFEcgFrHCRWEt41QtZBVJRpGHLOqdsRY6RoHQJRijB1nHx7mrudmgNbCOEXT63X0g4k_dDBe7_-MfqW7sNEcFSOC4ICTxwEx4Klp0oNPFvrejBDmpKkQvOYS1_kPlNeSccZLRN_9hd6HOY6oxC-KC1KV8g_VmR40ahdwRbsdqheC4eECSaRO_0Hha2HwNozgPNb3Gt7vNSAzwfepM3NK-vLudp8lD6yNIaUIbicdJXprKr11jd66BjfXaCpseftU8l3Dbxexnxb3xBM</recordid><startdate>20140707</startdate><enddate>20140707</enddate><creator>Visser, Marike</creator><creator>Maree, Hans J</creator><creator>Rees, D Jasper G</creator><creator>Burger, Johan T</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</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>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</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>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>7TM</scope><scope>5PM</scope></search><sort><creationdate>20140707</creationdate><title>High-throughput sequencing reveals small RNAs involved in ASGV infection</title><author>Visser, Marike ; Maree, Hans J ; Rees, D Jasper G ; Burger, Johan T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c558t-722d05b7b6a60b9e4a84ee1cf401504db58956775b30f3c89f0ac6fbfee088333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Apple stem grooving virus</topic><topic>Base Sequence</topic><topic>Disease Resistance - genetics</topic><topic>Gene Expression Regulation, Plant</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Health aspects</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Host-Pathogen Interactions</topic><topic>Infections</topic><topic>Malus</topic><topic>Malus - genetics</topic><topic>Malus - metabolism</topic><topic>Malus - virology</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Phylogeny</topic><topic>Physiological aspects</topic><topic>Plant Diseases - genetics</topic><topic>Plant Diseases - virology</topic><topic>Plant Viruses - physiology</topic><topic>RNA, Plant - genetics</topic><topic>RNA, Plant - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>RNA, Transfer - genetics</topic><topic>RNA, Transfer - metabolism</topic><topic>Sequence Analysis, RNA</topic><topic>Studies</topic><topic>Viral infections</topic><topic>Virulence (Microbiology)</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Visser, Marike</creatorcontrib><creatorcontrib>Maree, Hans J</creatorcontrib><creatorcontrib>Rees, D Jasper G</creatorcontrib><creatorcontrib>Burger, Johan T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</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 & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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 China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Visser, Marike</au><au>Maree, Hans J</au><au>Rees, D Jasper G</au><au>Burger, Johan T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-throughput sequencing reveals small RNAs involved in ASGV infection</atitle><jtitle>BMC genomics</jtitle><addtitle>BMC Genomics</addtitle><date>2014-07-07</date><risdate>2014</risdate><volume>15</volume><issue>1</issue><spage>568</spage><epage>568</epage><pages>568-568</pages><artnum>568</artnum><issn>1471-2164</issn><eissn>1471-2164</eissn><abstract>Plant small RNAs (sRNAs) associated with virulent virus infections have been reported by previous studies, while the involvement of sRNAs in latent virus infection remains largely uncharacterised. Apple trees show a high degree of resistance and tolerance to viral infections. We analysed two sRNA deep sequencing datasets, prepared from different RNA size fractions, to identify sRNAs involved in Apple stem grooving virus (ASGV) infection.
sRNA analysis revealed virus-derived siRNAs (vsiRNAs) originating from two ASGV genetic variants. A vsiRNA profile for one of the ASGV variants was also generated showing an increase in siRNA production towards the 3' end of the virus genome. Virus-derived sRNAs longer than those previously analysed were also observed in the sequencing data. Additionally, tRNA-derived sRNAs were identified and characterised. These sRNAs covered a broad size-range and originated from both ends of the mature tRNAs as well as from their central regions. Several tRNA-derived sRNAs showed differential regulation due to ASGV infection. No changes in microRNA, natural-antisense transcript siRNA, phased-siRNA and repeat-associated siRNA levels were observed.
This study is the first report on the apple sRNA-response to virus infection. The results revealed the vsiRNAs profile of an ASGV variant, as well as the alteration of the tRNA-derived sRNA profile in response to latent virus infection. It also highlights the importance of library preparation in the interpretation of high-throughput sequencing data.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24998458</pmid><doi>10.1186/1471-2164-15-568</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1471-2164 |
| ispartof | BMC genomics, 2014-07, Vol.15 (1), p.568-568, Article 568 |
| issn | 1471-2164 1471-2164 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4118050 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; SpringerLink Journals - AutoHoldings; PubMed Central Open Access; Springer Nature OA Free Journals |
| subjects | Analysis Apple stem grooving virus Base Sequence Disease Resistance - genetics Gene Expression Regulation, Plant Genetic aspects Genomes Genomics Health aspects High-Throughput Nucleotide Sequencing Host-Pathogen Interactions Infections Malus Malus - genetics Malus - metabolism Malus - virology Medical research Medicine, Experimental Phylogeny Physiological aspects Plant Diseases - genetics Plant Diseases - virology Plant Viruses - physiology RNA, Plant - genetics RNA, Plant - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism RNA, Transfer - genetics RNA, Transfer - metabolism Sequence Analysis, RNA Studies Viral infections Virulence (Microbiology) Viruses |
| title | High-throughput sequencing reveals small RNAs involved in ASGV infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T16%3A26%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High-throughput%20sequencing%20reveals%20small%20RNAs%20involved%20in%20ASGV%20infection&rft.jtitle=BMC%20genomics&rft.au=Visser,%20Marike&rft.date=2014-07-07&rft.volume=15&rft.issue=1&rft.spage=568&rft.epage=568&rft.pages=568-568&rft.artnum=568&rft.issn=1471-2164&rft.eissn=1471-2164&rft_id=info:doi/10.1186/1471-2164-15-568&rft_dat=%3Cgale_pubme%3EA539565945%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1549450726&rft_id=info:pmid/24998458&rft_galeid=A539565945&rfr_iscdi=true |