{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:23:45Z","timestamp":1762608225308,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejer\u00eda de Salud, Junta de Andaluc\u00eda","award":["PI\u20100173\u20102017"],"award-info":[{"award-number":["PI\u20100173\u20102017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. Although most of the SLE-associated loci are located in regulatory regions, there is a lack of global information about transcription factor (TFs) activities, the mode of regulation of the TFs, or the cell or sample-specific regulatory circuits. The aim of this work is to decipher TFs implicated in SLE. Methods: In order to decipher regulatory mechanisms in SLE, we have inferred TF activities from transcriptomic data for almost all human TFs, defined clusters of SLE patients based on the estimated TF activities and analyzed the differential activity patterns among SLE and healthy samples in two different cohorts. The Transcription Factor activity matrix was used to stratify SLE patients and define sets of TFs with statistically significant differential activity among the disease and control samples. Results: TF activities were able to identify two main subgroups of patients characterized by distinct neutrophil-to-lymphocyte ratio (NLR), with consistent patterns in two independent datasets\u2014one from pediatric patients and other from adults. Furthermore, after contrasting all subgroups of patients and controls, we obtained a significant and robust list of 14 TFs implicated in the dysregulation of SLE by different mechanisms and pathways. Among them, well-known regulators of SLE, such as STAT or IRF, were found, but others suggest new pathways that might have important roles in SLE. Conclusions: These results provide a foundation to comprehend the regulatory mechanism underlying SLE and the established regulatory factors behind SLE heterogeneity that could be potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/life11040299","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:23:17Z","timestamp":1617261797000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcription Factor Activity Inference in Systemic Lupus Erythematosus"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-117X","authenticated-orcid":false,"given":"Raul","family":"Lopez-Dominguez","sequence":"first","affiliation":[{"name":"Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Toro-Dominguez","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5186-0735","authenticated-orcid":false,"given":"Jordi","family":"Martorell-Marugan","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain"},{"name":"Atrys Health S.A., 08025 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-4962","authenticated-orcid":false,"given":"Adrian","family":"Garcia-Moreno","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3060-5786","authenticated-orcid":false,"given":"Christian","family":"Holland","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Computational Biomedicine, Heidelberg University, 69120 Heidelberg, Germany"},{"name":"Joint Research Center for Computational Biomedicine, Faculty of Medicine, RWTH Aachen University, 52062 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-8976","authenticated-orcid":false,"given":"Julio","family":"Saez-Rodriguez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Computational Biomedicine, Heidelberg University, 69120 Heidelberg, Germany"},{"name":"Joint Research Center for Computational Biomedicine, Faculty of Medicine, RWTH Aachen University, 52062 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5003-3503","authenticated-orcid":false,"given":"Daniel","family":"Goldman","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Petri","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-4154","authenticated-orcid":false,"given":"Marta","family":"Alarcon-Riquelme","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain"},{"name":"Unit of Chronic Inflammatory Diseases, Institute of Environmental Medicine, Karolinska Institutet, 17177 Solna, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-7255","authenticated-orcid":false,"given":"Pedro","family":"Carmona-Saez","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain"},{"name":"Joint Research Center for Computational Biomedicine, Faculty of Medicine, RWTH Aachen University, 52062 Aachen, Germany"},{"name":"Biostatistics, Department of Statistics, Faculty of Medicine, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.molmed.2017.05.006","article-title":"Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective","volume":"23","author":"Moulton","year":"2017","journal-title":"Trends Mol. 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