Transcriptome Analysis Reveals Differential Splicing Events in IPF Lung Tissue
Identifieur interne : 000B12 ( Main/Exploration ); précédent : 000B11; suivant : 000B13Transcriptome Analysis Reveals Differential Splicing Events in IPF Lung Tissue
Auteurs : Tracy Nance [États-Unis] ; Kevin S. Smith [États-Unis] ; Vanessa Anaya [États-Unis] ; Rhea Richardson [États-Unis] ; Lawrence Ho [États-Unis] ; Mauro Pala [États-Unis] ; Sara Mostafavi [États-Unis] ; Alexis Battle [États-Unis] ; Carol Feghali-Bostwick [États-Unis] ; Glenn Rosen [États-Unis] ; Stephen B. Montgomery [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- Analyse de profil d'expression de gènes, Analyse de regroupements, Collagène de type VI (génétique), Démographie, Exons (génétique), Fibrose pulmonaire idiopathique (génétique), Humains, Logiciel, Molécules d'adhérence cellulaire (génétique), Polymorphisme de nucléotide simple (génétique), Poumon (anatomopathologie), Poumon (métabolisme), Reproductibilité des résultats, Réaction de polymérisation en chaîne, Régulation négative (génétique), Régulation positive (génétique), Réseaux de régulation génique (génétique), Épissage alternatif (génétique), Étude d'association pangénomique.
- MESH :
- anatomopathologie : Poumon.
- génétique : Collagène de type VI, Exons, Fibrose pulmonaire idiopathique, Molécules d'adhérence cellulaire, Polymorphisme de nucléotide simple, Régulation négative, Régulation positive, Réseaux de régulation génique, Épissage alternatif.
- métabolisme : Poumon.
- Analyse de profil d'expression de gènes, Analyse de regroupements, Démographie, Humains, Logiciel, Reproductibilité des résultats, Réaction de polymérisation en chaîne, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Alternative Splicing (genetics), Cell Adhesion Molecules (genetics), Cluster Analysis, Collagen Type VI (genetics), Demography, Down-Regulation (genetics), Exons (genetics), Gene Expression Profiling, Gene Regulatory Networks (genetics), Genome-Wide Association Study, Humans, Idiopathic Pulmonary Fibrosis (genetics), Lung (metabolism), Lung (pathology), Polymerase Chain Reaction, Polymorphism, Single Nucleotide (genetics), Reproducibility of Results, Software, Up-Regulation (genetics).
- MESH :
- chemical , genetics : Cell Adhesion Molecules, Collagen Type VI.
- genetics : Alternative Splicing, Down-Regulation, Exons, Gene Regulatory Networks, Idiopathic Pulmonary Fibrosis, Polymorphism, Single Nucleotide, Up-Regulation.
- metabolism : Lung.
- pathology : Lung.
- Cluster Analysis, Demography, Gene Expression Profiling, Genome-Wide Association Study, Humans, Polymerase Chain Reaction, Reproducibility of Results, Software.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a complex disease in which a multitude of proteins and networks are disrupted. Interrogation of the transcriptome through RNA sequencing (RNA-Seq) enables the determination of genes whose differential expression is most significant in IPF, as well as the detection of alternative splicing events which are not easily observed with traditional microarray experiments. We sequenced messenger RNA from 8 IPF lung samples and 7 healthy controls on an Illumina HiSeq 2000, and found evidence for substantial differential gene expression and differential splicing. 873 genes were differentially expressed in IPF (FDR<5%), and 440 unique genes had significant differential splicing events in at least one exonic region (FDR<5%). We used qPCR to validate the differential exon usage in the second and third most significant exonic regions, in the genes COL6A3 (RNA-Seq adjusted pval = 7.18e-10) and POSTN (RNA-Seq adjusted pval = 2.06e-09), which encode the extracellular matrix proteins collagen alpha-3(VI) and periostin. The increased gene-level expression of periostin has been associated with IPF and its clinical progression, but its differential splicing has not been studied in the context of this disease. Our results suggest that alternative splicing of these and other genes may be involved in the pathogenesis of IPF. We have developed an interactive web application which allows users to explore the results of our RNA-Seq experiment, as well as those of two previously published microarray experiments, and we hope that this will serve as a resource for future investigations of gene regulation in IPF.
Url:
DOI: 10.1371/journal.pone.0092111
PubMed: 24647608
PubMed Central: 3960165
Affiliations:
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Le document en format XML
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Smith</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pathology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Anaya, Vanessa" sort="Anaya, Vanessa" uniqKey="Anaya V" first="Vanessa" last="Anaya">Vanessa Anaya</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pathology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Richardson, Rhea" sort="Richardson, Rhea" uniqKey="Richardson R" first="Rhea" last="Richardson">Rhea Richardson</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pathology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ho, Lawrence" sort="Ho, Lawrence" uniqKey="Ho L" first="Lawrence" last="Ho">Lawrence Ho</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Pala, Mauro" sort="Pala, Mauro" uniqKey="Pala M" first="Mauro" last="Pala">Mauro Pala</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pathology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Mostafavi, Sara" sort="Mostafavi, Sara" uniqKey="Mostafavi S" first="Sara" last="Mostafavi">Sara Mostafavi</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Department of Computer Science, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Computer Science, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Battle, Alexis" sort="Battle, Alexis" uniqKey="Battle A" first="Alexis" last="Battle">Alexis Battle</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Department of Computer Science, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Computer Science, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Feghali Bostwick, Carol" sort="Feghali Bostwick, Carol" uniqKey="Feghali Bostwick C" first="Carol" last="Feghali-Bostwick">Carol Feghali-Bostwick</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Rosen, Glenn" sort="Rosen, Glenn" uniqKey="Rosen G" first="Glenn" last="Rosen">Glenn Rosen</name><affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Montgomery, Stephen B" sort="Montgomery, Stephen B" uniqKey="Montgomery S" first="Stephen B." last="Montgomery">Stephen B. Montgomery</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pathology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University, Stanford, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alternative Splicing (genetics)</term><term>Cell Adhesion Molecules (genetics)</term><term>Cluster Analysis</term><term>Collagen Type VI (genetics)</term><term>Demography</term><term>Down-Regulation (genetics)</term><term>Exons (genetics)</term><term>Gene Expression Profiling</term><term>Gene Regulatory Networks (genetics)</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Idiopathic Pulmonary Fibrosis (genetics)</term><term>Lung (metabolism)</term><term>Lung (pathology)</term><term>Polymerase Chain Reaction</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Reproducibility of Results</term><term>Software</term><term>Up-Regulation (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Analyse de regroupements</term><term>Collagène de type VI (génétique)</term><term>Démographie</term><term>Exons (génétique)</term><term>Fibrose pulmonaire idiopathique (génétique)</term><term>Humains</term><term>Logiciel</term><term>Molécules d'adhérence cellulaire (génétique)</term><term>Polymorphisme de nucléotide simple (génétique)</term><term>Poumon (anatomopathologie)</term><term>Poumon (métabolisme)</term><term>Reproductibilité des résultats</term><term>Réaction de polymérisation en chaîne</term><term>Régulation négative (génétique)</term><term>Régulation positive (génétique)</term><term>Réseaux de régulation génique (génétique)</term><term>Épissage alternatif (génétique)</term><term>Étude d'association pangénomique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cell Adhesion Molecules</term><term>Collagen Type VI</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alternative Splicing</term><term>Down-Regulation</term><term>Exons</term><term>Gene Regulatory Networks</term><term>Idiopathic Pulmonary Fibrosis</term><term>Polymorphism, Single Nucleotide</term><term>Up-Regulation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Collagène de type VI</term><term>Exons</term><term>Fibrose pulmonaire idiopathique</term><term>Molécules d'adhérence cellulaire</term><term>Polymorphisme de nucléotide simple</term><term>Régulation négative</term><term>Régulation positive</term><term>Réseaux de régulation génique</term><term>Épissage alternatif</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cluster Analysis</term><term>Demography</term><term>Gene Expression Profiling</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Polymerase Chain Reaction</term><term>Reproducibility of Results</term><term>Software</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Analyse de regroupements</term><term>Démographie</term><term>Humains</term><term>Logiciel</term><term>Reproductibilité des résultats</term><term>Réaction de polymérisation en chaîne</term><term>Étude d'association pangénomique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Idiopathic pulmonary fibrosis (IPF) is a complex disease in which a multitude of proteins and networks are disrupted. Interrogation of the transcriptome through RNA sequencing (RNA-Seq) enables the determination of genes whose differential expression is most significant in IPF, as well as the detection of alternative splicing events which are not easily observed with traditional microarray experiments. We sequenced messenger RNA from 8 IPF lung samples and 7 healthy controls on an Illumina HiSeq 2000, and found evidence for substantial differential gene expression and differential splicing. 873 genes were differentially expressed in IPF (FDR<5%), and 440 unique genes had significant differential splicing events in at least one exonic region (FDR<5%). We used qPCR to validate the differential exon usage in the second and third most significant exonic regions, in the genes COL6A3 (RNA-Seq adjusted pval = 7.18e-10) and POSTN (RNA-Seq adjusted pval = 2.06e-09), which encode the extracellular matrix proteins collagen alpha-3(VI) and periostin. The increased gene-level expression of periostin has been associated with IPF and its clinical progression, but its differential splicing has not been studied in the context of this disease. Our results suggest that alternative splicing of these and other genes may be involved in the pathogenesis of IPF. We have developed an interactive web application which allows users to explore the results of our RNA-Seq experiment, as well as those of two previously published microarray experiments, and we hope that this will serve as a resource for future investigations of gene regulation in IPF.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mushiroda, T" uniqKey="Mushiroda T">T Mushiroda</name></author><author><name sortKey="Wattanapokayakit, S" uniqKey="Wattanapokayakit S">S Wattanapokayakit</name></author><author><name sortKey="Takahashi, A" uniqKey="Takahashi A">A Takahashi</name></author><author><name sortKey="Nukiwa, T" uniqKey="Nukiwa T">T Nukiwa</name></author><author><name sortKey="Kudoh, S" uniqKey="Kudoh S">S Kudoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seibold, Ma" uniqKey="Seibold M">MA Seibold</name></author><author><name sortKey="Wise, Al" uniqKey="Wise A">AL 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Hakonarson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li><li>Pennsylvanie</li><li>Washington (État)</li></region><settlement><li>Seattle</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Nance, Tracy" sort="Nance, Tracy" uniqKey="Nance T" first="Tracy" last="Nance">Tracy Nance</name></region><name sortKey="Anaya, Vanessa" sort="Anaya, Vanessa" uniqKey="Anaya V" first="Vanessa" last="Anaya">Vanessa Anaya</name><name sortKey="Battle, Alexis" sort="Battle, Alexis" uniqKey="Battle A" first="Alexis" last="Battle">Alexis Battle</name><name sortKey="Feghali Bostwick, Carol" sort="Feghali Bostwick, Carol" uniqKey="Feghali Bostwick C" first="Carol" last="Feghali-Bostwick">Carol Feghali-Bostwick</name><name sortKey="Ho, Lawrence" sort="Ho, Lawrence" uniqKey="Ho L" first="Lawrence" last="Ho">Lawrence Ho</name><name sortKey="Montgomery, Stephen B" sort="Montgomery, Stephen B" uniqKey="Montgomery S" first="Stephen B." last="Montgomery">Stephen B. Montgomery</name><name sortKey="Mostafavi, Sara" sort="Mostafavi, Sara" uniqKey="Mostafavi S" first="Sara" last="Mostafavi">Sara Mostafavi</name><name sortKey="Pala, Mauro" sort="Pala, Mauro" uniqKey="Pala M" first="Mauro" last="Pala">Mauro Pala</name><name sortKey="Richardson, Rhea" sort="Richardson, Rhea" uniqKey="Richardson R" first="Rhea" last="Richardson">Rhea Richardson</name><name sortKey="Rosen, Glenn" sort="Rosen, Glenn" uniqKey="Rosen G" first="Glenn" last="Rosen">Glenn Rosen</name><name sortKey="Smith, Kevin S" sort="Smith, Kevin S" uniqKey="Smith K" first="Kevin S." last="Smith">Kevin S. Smith</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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