Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways
Several studies have identified genes that are differentially expressed in atopic dermatitis (AD) compared to normal skin. However, there is also considerable variation in the list of differentially expressed genes (DEGs) reported by different groups and the exact cause of AD is still not fully unde...
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| creator | Ghosh, Debajyoti Ding, Lili Sivaprasad, Umasundari Geh, Esmond Biagini Myers, Jocelyn Bernstein, Jonathan A Khurana Hershey, Gurjit K Mersha, Tesfaye B |
| description | Several studies have identified genes that are differentially expressed in atopic dermatitis (AD) compared to normal skin. However, there is also considerable variation in the list of differentially expressed genes (DEGs) reported by different groups and the exact cause of AD is still not fully understood. Using a rank-based approach, we analyzed gene expression data from five different microarray studies, comprising a total of 127 samples and more than 250,000 transcripts. A total of 89 AD gene expression signatures '89ADGES', including FLG gene, were identified to show dysregulation consistently across these studies. Using a Support Vector Machine, we showed that the '89ADGES' discriminates AD from normal skin with 98% predictive accuracy. Functional annotation of these genes implicated their roles in immune responses (e.g., betadefensin, microseminoprotein), keratinocyte differentiation/epidermal development (e.g., FLG, CORIN, AQP, LOR, KRT16), inflammation (e.g., IL37, IL27RA, CCL18) and lipid metabolism (e.g., AKR1B10, FAD7, FAR2). Subsequently, we validated a subset of signature genes using quantitative PCR in a mouse model. Using a bioinformatic approach, we identified keratinocyte pathway over-represented (P = |
| doi_str_mv | 10.1371/journal.pone.0144316 |
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However, there is also considerable variation in the list of differentially expressed genes (DEGs) reported by different groups and the exact cause of AD is still not fully understood. Using a rank-based approach, we analyzed gene expression data from five different microarray studies, comprising a total of 127 samples and more than 250,000 transcripts. A total of 89 AD gene expression signatures '89ADGES', including FLG gene, were identified to show dysregulation consistently across these studies. Using a Support Vector Machine, we showed that the '89ADGES' discriminates AD from normal skin with 98% predictive accuracy. Functional annotation of these genes implicated their roles in immune responses (e.g., betadefensin, microseminoprotein), keratinocyte differentiation/epidermal development (e.g., FLG, CORIN, AQP, LOR, KRT16), inflammation (e.g., IL37, IL27RA, CCL18) and lipid metabolism (e.g., AKR1B10, FAD7, FAR2). Subsequently, we validated a subset of signature genes using quantitative PCR in a mouse model. Using a bioinformatic approach, we identified keratinocyte pathway over-represented (P = <0.0006) among the 89 signature genes. Keratinocytes are known to play a major role in barrier function due to their location in the epidermis. Our result suggests that besides immune- mediated pathway, skin barrier pathways such as the keratinocyte differentiation pathway play a key role in AD pathogenesis. A better understanding of the role of keratinocytes in AD will be important for developing novel "barrier therapy" for this disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0144316</identifier><identifier>PMID: 26717000</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Annotations ; Asthma ; Atopic dermatitis ; Case-Control Studies ; CCL18 protein ; Cell Differentiation - genetics ; Cluster Analysis ; Computational Biology - methods ; Data analysis ; Data processing ; Databases, Genetic ; Datasets ; Dermatitis ; Dermatitis, Atopic - genetics ; Dermatitis, Atopic - metabolism ; Dermatology ; Development and progression ; Differentiation ; Discriminant Analysis ; Disease ; DNA microarrays ; Eczema ; Endocrinology ; Epidermis ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Genes ; Genetic aspects ; Genotypes ; Health aspects ; Hospitals ; Humans ; Identification and classification ; Immune response ; Immunology ; Innovations ; Internal medicine ; Keratinocytes ; Keratinocytes - cytology ; Keratinocytes - metabolism ; Ligands ; Lipid metabolism ; Medicine ; Metabolism ; Mice ; Molecular Sequence Annotation ; Molecular targeted therapy ; Pathogenesis ; Pathways ; Pediatrics ; Principal components analysis ; Reproducibility of Results ; Rheumatology ; Signal Transduction ; Skin ; Studies ; Support Vector Machine ; Transcription (Genetics) ; Transcriptome</subject><ispartof>PloS one, 2015-12, Vol.10 (12), p.e0144316-e0144316</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Ghosh 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>2015 Ghosh et al 2015 Ghosh et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-4e82c522619a1362c9aceb48fda8b1284cc239ae2196f0f557c42e164812b2593</citedby><cites>FETCH-LOGICAL-c758t-4e82c522619a1362c9aceb48fda8b1284cc239ae2196f0f557c42e164812b2593</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/PMC4696650/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696650/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26717000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Simon, Michel</contributor><creatorcontrib>Ghosh, Debajyoti</creatorcontrib><creatorcontrib>Ding, Lili</creatorcontrib><creatorcontrib>Sivaprasad, Umasundari</creatorcontrib><creatorcontrib>Geh, Esmond</creatorcontrib><creatorcontrib>Biagini Myers, Jocelyn</creatorcontrib><creatorcontrib>Bernstein, Jonathan A</creatorcontrib><creatorcontrib>Khurana Hershey, Gurjit K</creatorcontrib><creatorcontrib>Mersha, Tesfaye B</creatorcontrib><title>Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Several studies have identified genes that are differentially expressed in atopic dermatitis (AD) compared to normal skin. However, there is also considerable variation in the list of differentially expressed genes (DEGs) reported by different groups and the exact cause of AD is still not fully understood. Using a rank-based approach, we analyzed gene expression data from five different microarray studies, comprising a total of 127 samples and more than 250,000 transcripts. A total of 89 AD gene expression signatures '89ADGES', including FLG gene, were identified to show dysregulation consistently across these studies. Using a Support Vector Machine, we showed that the '89ADGES' discriminates AD from normal skin with 98% predictive accuracy. Functional annotation of these genes implicated their roles in immune responses (e.g., betadefensin, microseminoprotein), keratinocyte differentiation/epidermal development (e.g., FLG, CORIN, AQP, LOR, KRT16), inflammation (e.g., IL37, IL27RA, CCL18) and lipid metabolism (e.g., AKR1B10, FAD7, FAR2). Subsequently, we validated a subset of signature genes using quantitative PCR in a mouse model. Using a bioinformatic approach, we identified keratinocyte pathway over-represented (P = <0.0006) among the 89 signature genes. Keratinocytes are known to play a major role in barrier function due to their location in the epidermis. Our result suggests that besides immune- mediated pathway, skin barrier pathways such as the keratinocyte differentiation pathway play a key role in AD pathogenesis. A better understanding of the role of keratinocytes in AD will be important for developing novel "barrier therapy" for this disease.</description><subject>Animals</subject><subject>Annotations</subject><subject>Asthma</subject><subject>Atopic dermatitis</subject><subject>Case-Control Studies</subject><subject>CCL18 protein</subject><subject>Cell Differentiation - genetics</subject><subject>Cluster Analysis</subject><subject>Computational Biology - methods</subject><subject>Data analysis</subject><subject>Data processing</subject><subject>Databases, Genetic</subject><subject>Datasets</subject><subject>Dermatitis</subject><subject>Dermatitis, Atopic - genetics</subject><subject>Dermatitis, Atopic - metabolism</subject><subject>Dermatology</subject><subject>Development and progression</subject><subject>Differentiation</subject><subject>Discriminant Analysis</subject><subject>Disease</subject><subject>DNA microarrays</subject><subject>Eczema</subject><subject>Endocrinology</subject><subject>Epidermis</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulatory Networks</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genotypes</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Innovations</subject><subject>Internal medicine</subject><subject>Keratinocytes</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - metabolism</subject><subject>Ligands</subject><subject>Lipid metabolism</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Molecular Sequence Annotation</subject><subject>Molecular targeted therapy</subject><subject>Pathogenesis</subject><subject>Pathways</subject><subject>Pediatrics</subject><subject>Principal components analysis</subject><subject>Reproducibility of Results</subject><subject>Rheumatology</subject><subject>Signal Transduction</subject><subject>Skin</subject><subject>Studies</subject><subject>Support Vector Machine</subject><subject>Transcription (Genetics)</subject><subject>Transcriptome</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQgCMEYmPwHyCIhITgocW_4iQvk8oGo9LQ0DZ4tS7OpfXkxp3tFPrf423d1KI9ID_Eunz32T77suw1JWPKS_rpyg2-Bzteuh7HhArBqXyS7dOas5FkhD_dmu9lL0K4IqTglZTPsz0mS1oSQvaz6--DjWZpMb_00AftzTK6BebHECGfJP86mJCf4wrBhvyzcdbNjAZr1ylocQV9zCfRLY3Oj9EvIJqY-Asz6yEOHvMT7DHk0Lf5D4jz37AOL7NnXXLhq833IPv59cvl0bfR6dnJ9GhyOtJlUcWRwIrpgjFJa6BcMl2DxkZUXQtVQ1kltGa8BmS0lh3piqLUgiGVoqKsYUXND7K3d96ldUFtqhUULQtWVJxUMhHTO6J1cKWW3izAr5UDo24Dzs8U-Gi0RSUZNAR42daNEE3aQim1oILVyJuS0za5DjerDc0CW4199GB3pLt_ejNXM7dSQtZSFiQJPmwE3l0PGKJamKDRWujRDbf75umOhaAJffcP-vjpNtQM0gFM37m0rr6RqongVcnKIikPsvEjVBotLoxOT6szKb6T8HEnITER_8QZDCGo6cX5_7Nnv3bZ91vsPD23OA_ODtG4PuyC4g7U3oXgsXsoMiXqpjPuq6FuOkNtOiOlvdm-oIek-1bgfwHFSQkY</recordid><startdate>20151230</startdate><enddate>20151230</enddate><creator>Ghosh, Debajyoti</creator><creator>Ding, Lili</creator><creator>Sivaprasad, Umasundari</creator><creator>Geh, Esmond</creator><creator>Biagini Myers, Jocelyn</creator><creator>Bernstein, Jonathan A</creator><creator>Khurana Hershey, Gurjit K</creator><creator>Mersha, Tesfaye B</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20151230</creationdate><title>Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways</title><author>Ghosh, Debajyoti ; Ding, Lili ; Sivaprasad, Umasundari ; Geh, Esmond ; Biagini Myers, Jocelyn ; Bernstein, Jonathan A ; Khurana Hershey, Gurjit K ; Mersha, Tesfaye B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-4e82c522619a1362c9aceb48fda8b1284cc239ae2196f0f557c42e164812b2593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Annotations</topic><topic>Asthma</topic><topic>Atopic dermatitis</topic><topic>Case-Control Studies</topic><topic>CCL18 protein</topic><topic>Cell Differentiation - genetics</topic><topic>Cluster Analysis</topic><topic>Computational Biology - methods</topic><topic>Data analysis</topic><topic>Data processing</topic><topic>Databases, Genetic</topic><topic>Datasets</topic><topic>Dermatitis</topic><topic>Dermatitis, Atopic - genetics</topic><topic>Dermatitis, Atopic - metabolism</topic><topic>Dermatology</topic><topic>Development and progression</topic><topic>Differentiation</topic><topic>Discriminant Analysis</topic><topic>Disease</topic><topic>DNA microarrays</topic><topic>Eczema</topic><topic>Endocrinology</topic><topic>Epidermis</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Gene Regulatory Networks</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genotypes</topic><topic>Health aspects</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Immune response</topic><topic>Immunology</topic><topic>Innovations</topic><topic>Internal medicine</topic><topic>Keratinocytes</topic><topic>Keratinocytes - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghosh, Debajyoti</au><au>Ding, Lili</au><au>Sivaprasad, Umasundari</au><au>Geh, Esmond</au><au>Biagini Myers, Jocelyn</au><au>Bernstein, Jonathan A</au><au>Khurana Hershey, Gurjit K</au><au>Mersha, Tesfaye B</au><au>Simon, Michel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-12-30</date><risdate>2015</risdate><volume>10</volume><issue>12</issue><spage>e0144316</spage><epage>e0144316</epage><pages>e0144316-e0144316</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Several studies have identified genes that are differentially expressed in atopic dermatitis (AD) compared to normal skin. However, there is also considerable variation in the list of differentially expressed genes (DEGs) reported by different groups and the exact cause of AD is still not fully understood. Using a rank-based approach, we analyzed gene expression data from five different microarray studies, comprising a total of 127 samples and more than 250,000 transcripts. A total of 89 AD gene expression signatures '89ADGES', including FLG gene, were identified to show dysregulation consistently across these studies. Using a Support Vector Machine, we showed that the '89ADGES' discriminates AD from normal skin with 98% predictive accuracy. Functional annotation of these genes implicated their roles in immune responses (e.g., betadefensin, microseminoprotein), keratinocyte differentiation/epidermal development (e.g., FLG, CORIN, AQP, LOR, KRT16), inflammation (e.g., IL37, IL27RA, CCL18) and lipid metabolism (e.g., AKR1B10, FAD7, FAR2). Subsequently, we validated a subset of signature genes using quantitative PCR in a mouse model. Using a bioinformatic approach, we identified keratinocyte pathway over-represented (P = <0.0006) among the 89 signature genes. Keratinocytes are known to play a major role in barrier function due to their location in the epidermis. Our result suggests that besides immune- mediated pathway, skin barrier pathways such as the keratinocyte differentiation pathway play a key role in AD pathogenesis. A better understanding of the role of keratinocytes in AD will be important for developing novel "barrier therapy" for this disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26717000</pmid><doi>10.1371/journal.pone.0144316</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1752583086 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Annotations Asthma Atopic dermatitis Case-Control Studies CCL18 protein Cell Differentiation - genetics Cluster Analysis Computational Biology - methods Data analysis Data processing Databases, Genetic Datasets Dermatitis Dermatitis, Atopic - genetics Dermatitis, Atopic - metabolism Dermatology Development and progression Differentiation Discriminant Analysis Disease DNA microarrays Eczema Endocrinology Epidermis Gene expression Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks Genes Genetic aspects Genotypes Health aspects Hospitals Humans Identification and classification Immune response Immunology Innovations Internal medicine Keratinocytes Keratinocytes - cytology Keratinocytes - metabolism Ligands Lipid metabolism Medicine Metabolism Mice Molecular Sequence Annotation Molecular targeted therapy Pathogenesis Pathways Pediatrics Principal components analysis Reproducibility of Results Rheumatology Signal Transduction Skin Studies Support Vector Machine Transcription (Genetics) Transcriptome |
| title | Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T09%3A54%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multiple%20Transcriptome%20Data%20Analysis%20Reveals%20Biologically%20Relevant%20Atopic%20Dermatitis%20Signature%20Genes%20and%20Pathways&rft.jtitle=PloS%20one&rft.au=Ghosh,%20Debajyoti&rft.date=2015-12-30&rft.volume=10&rft.issue=12&rft.spage=e0144316&rft.epage=e0144316&rft.pages=e0144316-e0144316&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0144316&rft_dat=%3Cgale_plos_%3EA438727575%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1752583086&rft_id=info:pmid/26717000&rft_galeid=A438727575&rft_doaj_id=oai_doaj_org_article_62ab0a37d9b44bda876c41429e3b731d&rfr_iscdi=true |