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Identification of miRNAs Potentially Involved in Bronchiolitis Obliterans Syndrome: A Computational Study
The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a com...
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Published in: | PloS one 2016-08, Vol.11 (8), p.e0161771-e0161771 |
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creator | Di Carlo, Stefano Rossi, Elena Politano, Gianfranco Inghilleri, Simona Morbini, Patrizia Calabrese, Fiorella Benso, Alfredo Savino, Alessandro Cova, Emanuela Zampieri, Davide Meloni, Federica |
description | The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs-miR-34a and miR-21 -was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline. |
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Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs-miR-34a and miR-21 -was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0161771</identifier><identifier>PMID: 27564214</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>A549 Cells ; Acute Disease ; Algorithms ; Animals ; Biology and life sciences ; Bronchiolitis ; Bronchiolitis obliterans ; Bronchiolitis Obliterans - genetics ; Bronchopneumonia ; Chronic Disease ; Computation ; Computer applications ; Computer Simulation ; Development and progression ; Disease ; Epigenesis, Genetic ; Epigenetics ; Experiments ; Filtration ; Gene expression ; Gene Expression Regulation ; Gene Regulatory Networks ; Genetic aspects ; Graft rejection ; Graft Rejection - pathology ; Humans ; In Situ Hybridization ; Lung cancer ; Lung transplantation ; Lung Transplantation - adverse effects ; Lungs ; Medicine and Health Sciences ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Pathogenesis ; Physiological aspects ; Pipelines ; Pulmonary fibrosis ; Rats ; Respiratory diseases ; Signal transduction ; Statistical analysis ; Thoracic surgery ; Transplants & implants ; Xenografts</subject><ispartof>PloS one, 2016-08, Vol.11 (8), p.e0161771-e0161771</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Di Carlo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Di Carlo et al 2016 Di Carlo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-49584eb6401063ceefff4eeab368e82099071647b683e90de07f0c251315d33</citedby><cites>FETCH-LOGICAL-c725t-49584eb6401063ceefff4eeab368e82099071647b683e90de07f0c251315d33</cites><orcidid>0000-0002-7512-5356</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1814320441/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1814320441?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25744,27915,27916,37003,37004,44581,53782,53784,74887</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27564214$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mallick, Bibekanand</contributor><creatorcontrib>Di Carlo, Stefano</creatorcontrib><creatorcontrib>Rossi, Elena</creatorcontrib><creatorcontrib>Politano, Gianfranco</creatorcontrib><creatorcontrib>Inghilleri, Simona</creatorcontrib><creatorcontrib>Morbini, Patrizia</creatorcontrib><creatorcontrib>Calabrese, Fiorella</creatorcontrib><creatorcontrib>Benso, Alfredo</creatorcontrib><creatorcontrib>Savino, Alessandro</creatorcontrib><creatorcontrib>Cova, Emanuela</creatorcontrib><creatorcontrib>Zampieri, Davide</creatorcontrib><creatorcontrib>Meloni, Federica</creatorcontrib><title>Identification of miRNAs Potentially Involved in Bronchiolitis Obliterans Syndrome: A Computational Study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs-miR-34a and miR-21 -was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline.</description><subject>A549 Cells</subject><subject>Acute Disease</subject><subject>Algorithms</subject><subject>Animals</subject><subject>Biology and life sciences</subject><subject>Bronchiolitis</subject><subject>Bronchiolitis obliterans</subject><subject>Bronchiolitis Obliterans - genetics</subject><subject>Bronchopneumonia</subject><subject>Chronic Disease</subject><subject>Computation</subject><subject>Computer applications</subject><subject>Computer Simulation</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Experiments</subject><subject>Filtration</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulatory Networks</subject><subject>Genetic aspects</subject><subject>Graft rejection</subject><subject>Graft Rejection - 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Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs-miR-34a and miR-21 -was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27564214</pmid><doi>10.1371/journal.pone.0161771</doi><tpages>e0161771</tpages><orcidid>https://orcid.org/0000-0002-7512-5356</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | A549 Cells Acute Disease Algorithms Animals Biology and life sciences Bronchiolitis Bronchiolitis obliterans Bronchiolitis Obliterans - genetics Bronchopneumonia Chronic Disease Computation Computer applications Computer Simulation Development and progression Disease Epigenesis, Genetic Epigenetics Experiments Filtration Gene expression Gene Expression Regulation Gene Regulatory Networks Genetic aspects Graft rejection Graft Rejection - pathology Humans In Situ Hybridization Lung cancer Lung transplantation Lung Transplantation - adverse effects Lungs Medicine and Health Sciences MicroRNA MicroRNAs MicroRNAs - genetics miRNA Pathogenesis Physiological aspects Pipelines Pulmonary fibrosis Rats Respiratory diseases Signal transduction Statistical analysis Thoracic surgery Transplants & implants Xenografts |
title | Identification of miRNAs Potentially Involved in Bronchiolitis Obliterans Syndrome: A Computational Study |
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