{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:55:12Z","timestamp":1753890912613,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Psoriasis is a chronic inflammatory skin disorder. Although it has been studied extensively, the molecular mechanisms driving the disease remain unclear. In this study, we utilized a tree-based machine learning approach to explore the gene regulatory networks underlying psoriasis. We then validated the regulators and their networks in an independent cohort. We identified some key regulators of psoriasis, which are candidates to serve as potential drug targets and disease severity biomarkers. According to the gene regulatory network that we identified, we suggest that interferon signaling represents a key pathway of psoriatic inflammation.<\/jats:p>","DOI":"10.3389\/fimmu.2022.921408","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T06:32:54Z","timestamp":1657175574000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Finding Gene Regulatory Networks in Psoriasis: Application of a Tree-Based Machine Learning Approach"],"prefix":"10.3389","volume":"13","author":[{"given":"Jingwen","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Schieler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 A. M.","family":"Borghans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanjian","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aridaman","family":"Pandit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.339","article-title":"Global Epidemiology of Psoriasis: A Systematic Review of Incidence and Prevalence","volume":"133","author":"Parisi","year":"2013","journal-title":"J Invest Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01549","article-title":"The Interplay Between Keratinocytes and Immune Cells in the Pathogenesis of Psoriasis","volume":"9","author":"Albanesi","year":"2018","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/1203475415584503","article-title":"IL-17a, IL-22, and IL-23 as Markers of Psoriasis Activity: A Cross-Sectional, Hospital-Based Study","volume":"19","author":"Fotiadou","year":"2015","journal-title":"J Cutaneous Med Surg"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.2147\/PTT.S64950","article-title":"Current Knowledge on Psoriasis and Autoimmune Diseases","volume":"6","author":"Ayala-Font\u00e1nez","year":"2016","journal-title":"Psoriasis (Auckland NZ)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28525","article-title":"Integrated Analysis of Gene Expression Profiles Identifies Transcription Factors Potentially Involved in Psoriasis Pathogenesis","volume":"120","author":"Zeng","year":"2019","journal-title":"J Cell Biochem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s42003-021-02991-5","article-title":"RegEnrich Gene Regulator Enrichment Analysis Reveals a Key Role of the ETS Transcription Factor Family in Interferon Signaling","volume":"5","author":"Tao","year":"2022","journal-title":"Commun Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.03.003","article-title":"RNA Sequencing Atopic Dermatitis Transcriptome Profiling Provides Insights Into Novel Disease Mechanisms With Potential Therapeutic Implications","volume":"135","author":"Su\u00e1rez-Fari\u00f1as","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-015-0208-5","article-title":"Proteogenomic Analysis of Psoriasis Reveals Discordant and Concordant Changes in mRNA and Protein Abundance","volume":"7","author":"Swindell","year":"2015","journal-title":"Genome Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13059-014-0570-4","article-title":"Analysis of Long Non-Coding RNAs Highlights Tissue-Specific Expression Patterns and Epigenetic Profiles in Normal and Psoriatic Skin","volume":"16","author":"Tsoi","year":"2015","journal-title":"Genome Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.07.054","article-title":"Transcriptional Determinants of Individualized Inflammatory Responses at Anatomically Separate Sites","volume":"141","author":"Tsoi","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.12.018","article-title":"Atopic Dermatitis Is an IL-13-Dominant Disease With Greater Molecular Heterogeneity Compared to Psoriasis","volume":"139","author":"Tsoi","year":"2019","journal-title":"J Invest Dermatol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41597-020-00696-8","article-title":"Manually Curated and Harmonised Transcriptomics Datasets of Psoriasis and Atopic Dermatitis Patients","volume":"7","author":"Federico","year":"2020","journal-title":"Sci Data"},{"key":"B13","doi-asserted-by":"publisher","first-page":"160018","DOI":"10.1038\/sdata.2016.18","article-title":"The FAIR Guiding Principles for Scientific Data Management and Stewardship","volume":"3","author":"Wilkinson","year":"2016","journal-title":"Sci Data"},{"key":"B14","first-page":"2021.11.26.469424","volume-title":"Interactions of host defense and hyper-keratinization in psoriasis","author":"Deng","year":"2021"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/art.21972","article-title":"Classification Criteria for Psoriatic Arthritis: Development of New Criteria From a Large International Study","volume":"54","author":"Taylor","year":"2006","journal-title":"Arthritis Rheum"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.108233","article-title":"The Development of Assessment of SpondyloArthritis International Society Classification Criteria for Axial Spondyloarthritis (Part II): Validation and Final Selection","volume":"68","author":"Rudwaleit","year":"2009","journal-title":"Ann Rheum Dis"},{"key":"B17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinf (Oxford England)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python Framework to Work With High-Throughput Sequencing Data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinf (Oxford England)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1159\/000250839","article-title":"Severe Psoriasis\u2014Oral Therapy With a New Retinoid","volume":"157","author":"Fredriksson","year":"1978","journal-title":"Dermatologica"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000520163","article-title":"Evaluation of Psoriasis Area and Severity Index Thresholds as Proxies for Systemic Inflammation on an Individual Patient Level","author":"Hoffmann","year":"2021","journal-title":"Dermatol (Basel Switzerland)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data With Deseq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","article-title":"Clusterprofiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (New York NY)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq675","article-title":"Cytoscape 2.8: New Features for Data Integration and Network Visualization","volume":"27","author":"Smoot","year":"2011","journal-title":"Bioinf (Oxford England)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010171","article-title":"Psoriasis: A STAT3-Centric View","volume":"19","author":"Calautti","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1186\/s12864-015-1508-2","article-title":"Transcriptional Landscape of Psoriasis Identifies the Involvement of IL36 and IL36RN","volume":"16","author":"Keermann","year":"2015","journal-title":"BMC Genomics"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.042242","article-title":"Proteomics of Skin Proteins in Psoriasis: From Discovery and Verification in a Mouse Model to Confirmation in Humans","volume":"14","author":"Lundberg","year":"2015","journal-title":"Mol Cell Proteomics: MCP"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2174\/156652408785160952","article-title":"Role of GATA-3 in Allergic Diseases","volume":"8","author":"Barnes","year":"2008","journal-title":"Curr Mol Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.jaci.2012.06.044","article-title":"Comparative Transcriptomic Analyses of Atopic Dermatitis and Psoriasis Reveal Shared Neutrophilic Inflammation","volume":"130","author":"Choy","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073687","article-title":"STAT3 Mutations in the Hyper-IgE Syndrome","volume":"357","author":"Holland","year":"2007","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080218","article-title":"Deficiency of Th17 Cells in Hyper IgE Syndrome Due to Mutations in STAT3","volume":"205","author":"Ma","year":"2008","journal-title":"J Exp Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nature06764","article-title":"Impaired T(H)17 Cell Differentiation in Subjects With Autosomal Dominant Hyper-IgE Syndrome","volume":"452","author":"Milner","year":"2008","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nature06096","article-title":"Dominant-Negative Mutations in the DNA-Binding Domain of STAT3 Cause Hyper-IgE Syndrome","volume":"448","author":"Minegishi","year":"2007","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S82599","article-title":"Profile of Tofacitinib Citrate and Its Potential in the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis","volume":"10","author":"Di Lernia","year":"2016","journal-title":"Drug Design Dev Ther"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.340","article-title":"Integrative Responses to IL-17 and TNF-\u03b1 in Human Keratinocytes Account for Key Inflammatory Pathogenic Circuits in Psoriasis","volume":"131","author":"Chiricozzi","year":"2011","journal-title":"J Invest Dermatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080751","article-title":"Novel Factors in the Pathogenesis of Psoriasis and Potential Drug Candidates are Found With Systems Biology Approach","volume":"8","author":"Manczinger","year":"2013","journal-title":"PLoS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jdermsci.2019.11.003","article-title":"Integrated microRNA\/mRNA Expression Profiling of the Skin of Psoriasis Patients","volume":"97","author":"Deli\u0107","year":"2020","journal-title":"J Dermatol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2009.04.002","article-title":"Unraveling the Genetics of Complex Diseases: Susceptibility Genes for Rheumatoid Arthritis and Psoriasis","volume":"21","author":"Li","year":"2009","journal-title":"Semin Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.210245","article-title":"Apolipoprotein L6, Induced in Atherosclerotic Lesions, Promotes Apoptosis and Blocks Beclin 1-Dependent Autophagy in Atherosclerotic Cells","volume":"286","author":"Zhaorigetu","year":"2011","journal-title":"J Biol Chem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00714-13","article-title":"Measles Virus Nonstructural C Protein Modulates Viral RNA Polymerase Activity by Interacting With Host Protein Shcbp1","volume":"87","author":"Ito","year":"2013","journal-title":"J Virol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16703","article-title":"Transcriptome Wide Analysis of Long Non-Coding RNA-Associated ceRNA Regulatory Circuits in Psoriasis","volume":"25","author":"Lin","year":"2021","journal-title":"J Cell Mol Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/all.15150","article-title":"Transcriptome-Based Identification of Novel Endotypes in Adult Atopic Dermatitis","volume":"77","author":"Lef\u00e8vre-Utile","year":"2022","journal-title":"Allergy"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.02.020","article-title":"Mechanisms of IFN-\u03b3\u2013Induced Apoptosis of Human Skin Keratinocytes in Patients With Atopic Dermatitis","volume":"129","author":"Rebane","year":"2012","journal-title":"J Allergy Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.921408\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T06:32:59Z","timestamp":1657175579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.921408\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,7]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2022.921408"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.921408","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2022,7,7]]},"article-number":"921408"}}