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Typically, miRNA regulation drives changes in the composition and levels of protein-coding RNA and of lncRNA, with targets being down-regulated when miRNAs are active. The term \u201cmiRNA activity\" is used to refer to this transcriptional effect of miRNAs. This study introduces miTEA-HiRes, a method designed to facilitate the evaluation of miRNA activity at high resolution. The method applies to single-cell transcriptomics, type-specific single-cell populations, and spatial transcriptomics data. By comparing different conditions, differential miRNA activity is inferred. For instance, miTEA-HiRes analysis of peripheral blood mononuclear cells comparing Multiple Sclerosis patients to control groups revealed differential activity of miR-20a-5p and others, consistent with the literature on miRNA underexpression in Multiple Sclerosis. We also show miR-519a-3p differential activity in specific cell populations.<\/jats:p>","DOI":"10.1038\/s42003-025-07454-9","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T12:38:34Z","timestamp":1737203914000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Inferring single-cell and spatial microRNA activity from transcriptomics data"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9261-3637","authenticated-orcid":false,"given":"Efrat","family":"Herbst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-8237","authenticated-orcid":false,"given":"Yael","family":"Mandel-Gutfreund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-5412","authenticated-orcid":false,"given":"Zohar","family":"Yakhini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1739-1170","authenticated-orcid":false,"given":"Hadas","family":"Biran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,18]]},"reference":[{"key":"7454_CR1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/nrg3162","volume":"13","author":"AE Pasquinelli","year":"2012","unstructured":"Pasquinelli, A. 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