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The ability to identify active regulons within a specific cell type, i.e., cell-type-specific regulons (CTSR), provides an extraordinary opportunity to pinpoint crucial regulators and target genes responsible for complex diseases. However, the identification of CTSRs from single-cell RNA-Seq (scRNA-Seq) data is computationally challenging. We introduce IRIS3, the first-of-its-kind web server for CTSR inference from scRNA-Seq data for human and mouse. IRIS3 is an easy-to-use server empowered by over 20 functionalities to support comprehensive interpretations and graphical visualizations of identified CTSRs. CTSR data can be used to reliably characterize and distinguish the corresponding cell type from others and can be combined with other computational or experimental analyses for biomedical studies. CTSRs can, therefore, aid in the discovery of major regulatory mechanisms and allow reliable constructions of global transcriptional regulation networks encoded in a specific cell type. The broader impact of IRIS3 includes, but is not limited to, investigation of complex diseases hierarchies and heterogeneity, causal gene regulatory network construction, and drug development. IRIS3 is freely accessible from https:\/\/bmbl.bmi.osumc.edu\/iris3\/ with no login requirement.<\/jats:p>","DOI":"10.1093\/nar\/gkaa394","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T19:12:08Z","timestamp":1588619528000},"page":"W275-W286","source":"Crossref","is-referenced-by-count":48,"title":["IRIS3: integrated cell-type-specific regulon inference server from single-cell RNA-Seq"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6269-398X","authenticated-orcid":false,"given":"Anjun","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cankun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhou","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith H","family":"Brennan","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Center for Brain and Spinal Cord Repair, Belford Center for Spinal Cord Injury, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"McDermaid","sequence":"first","affiliation":[{"name":"Imagenetics, Sanford Health, Sioux Falls, SD\u00a057104, USA"},{"name":"Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Vermillion, SD\u00a057069, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqiang","family":"Liu","sequence":"first","affiliation":[{"name":"School of Mathematics, Shandong University, Jinan\u00a0250100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical & Molecular Genetics, Indiana University, School of Medicine, Indianapolis, IN\u00a046202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip G","family":"Popovich","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Center for Brain and Spinal Cord Repair, Belford Center for Spinal Cord Injury, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3264-8392","authenticated-orcid":false,"given":"Qin","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"2020062614042086200_B1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nature21350","article-title":"Scaling single-cell genomics from phenomenology to mechanism","volume":"541","author":"Tanay","year":"2017","journal-title":"Nature"},{"key":"2020062614042086200_B2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.cels.2019.07.001","article-title":"Determination of the gene regulatory network of a Genome-Reduced bacterium highlights alternative regulation independent of transcription factors","volume":"9","author":"Yus","year":"2019","journal-title":"Cell Syst."},{"key":"2020062614042086200_B3","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/j.micinf.2006.03.018","article-title":"Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis","volume":"8","author":"Leyten","year":"2006","journal-title":"Microbes Infect."},{"key":"2020062614042086200_B4","doi-asserted-by":"crossref","first-page":"e1003731","DOI":"10.1371\/journal.pcbi.1003731","article-title":"iRegulon: from a gene list to a gene regulatory network using large motif and track collections","volume":"10","author":"Janky","year":"2014","journal-title":"PLoS Comput. 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