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Semi\u2010specific proteome searches, that enforce a theoretical enzymatic digestion to solely the N\u2010 or C\u2010terminal end, allow to identify of native protein termini or those arising from endogenous proteolytic activity (also referred to as \u201cneo\u2010N\u2010termini\u201d analysis or \u201cN\u2010terminomics\u201d). Nevertheless, deriving biological meaning from these search outputs can be challenging in terms of data mining and analysis. Thus, we introduce <jats:italic>TermineR<\/jats:italic>, a data analysis approach for the (1) annotation of peptides according to their enzymatic cleavage specificity and known protein processing features, (2) differential abundance and enrichment analysis of N\u2010terminal sequence patterns, and (3) visualization of neo\u2010N\u2010termini location. We illustrate the use of <jats:italic>TermineR<\/jats:italic> by applying it to tandem mass tag (TMT)\u2010based proteomics data of a mouse model of polycystic kidney disease, and assess the semi\u2010specific searches for biological interpretation of cleavage events and the variable contribution of proteolytic products to general protein abundance. The <jats:italic>TermineR<\/jats:italic> approach and example data are available as an R package at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/github.com\/MiguelCos\/TermineR\">https:\/\/github.com\/MiguelCos\/TermineR<\/jats:ext-link>.<\/jats:p>","DOI":"10.1002\/pmic.202300491","type":"journal-article","created":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T03:36:09Z","timestamp":1723260969000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["TermineR: Extracting information on endogenous proteolytic processing from shotgun proteomics data"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-3229","authenticated-orcid":false,"given":"Miguel","family":"Cosenza\u2010Contreras","sequence":"first","affiliation":[{"name":"Faculty of Biology University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine Institute for 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thien\u2010Ly Julia","family":"Dinh","sequence":"additional","affiliation":[{"name":"Faculty of Biology University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine Institute for Surgical Pathology Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Bernhard","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute for Surgical Pathology Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rogg","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute for Surgical Pathology Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Willems","sequence":"additional","affiliation":[{"name":"Department of Plant Biotechnology and Bioinformatics Ghent University  Ghent Belgium"},{"name":"VIB\u2010UGent Center for Plant Systems Biology  Ghent Belgium"},{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Center for Medical Biotechnology, VIB  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Stael","sequence":"additional","affiliation":[{"name":"Department of Plant Biotechnology and Bioinformatics Ghent University  Ghent Belgium"},{"name":"VIB\u2010UGent Center for Plant Systems Biology  Ghent Belgium"},{"name":"Department of Molecular Sciences, Uppsala BioCenter Swedish University of Agricultural Sciences and Linnean Center for Plant Biology  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0335-2242","authenticated-orcid":false,"given":"Pitter F.","family":"Huesgen","sequence":"additional","affiliation":[{"name":"Faculty of Biology University of Freiburg  Freiburg Germany"},{"name":"Centre for Integrative Biological Signaling Studies (CIBSS)  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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