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However, methods for inferring tumor phylogenies need to strike a balance between keeping reasonable running times and employing sophisticated evolution models. Binary characters, such as single-nucleotide variants and known mutations, which is our focus, is an example of a simple model that is able to capture most relevant cases\u2014but not copy number variants. On binary characters, most methods are designed for simpler models where mutations can only be accumulated under the infinite sites assumption; however, those models tend to be too simplistic for real case scenarios. While the most explored direction in the context of binary characters is to allow mutation losses, in this paper, we introduce an even more general model, where each mutation can be acquired and lost more than once. We describe this model, provide a simulated annealing approach exploiting this novel evolutionary framework, and show its accuracy on different sets of experimental evaluations when compared to less general models, and demonstrate potential application to real data.<\/jats:p>","DOI":"10.1007\/s00521-025-11474-1","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T11:56:59Z","timestamp":1753790219000},"page":"21545-21562","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer progression inference using a finite-state model to allow recurrences and losses of mutations"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-4887","authenticated-orcid":false,"given":"Simone","family":"Ciccolella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murray","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman","family":"Hajirasouliha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Della Vedova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"11474_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/nature16478","volume":"529","author":"AS Morrissy","year":"2016","unstructured":"Morrissy AS, Garzia L et al (2016) Divergent clonal selection dominates medulloblastoma at recurrence. 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