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However, traditional selective pressure analysis methods have treated all sites within a gene equally, such a gene-level model oversimplifies the complexity of cancer evolution. In this study, we introduced CN\/CS-calculator, a novel site-specific method that can capture selective pressures acting across different gene sites. By deciphering the interplay between the selection pattern and the function of a gene in oncogenesis, CN\/CS-calculator uncovers a unique class of mini-driver genes, which exhibit weak positive selection, with certain critical sites providing context-dependent promoter effects on the fitness of cancer subclones while others are constrained by evolutionary conservation. Our method emphasizes the importance of site-specific analysis in uncovering how subtle evolutionary forces shape cancer biology. The refined understanding offers new insights into the mechanisms of cancer heterogeneity and molecular evolution, with potential implications for advancing therapeutic strategies and prognostic assessments.<\/jats:p>","DOI":"10.1093\/bib\/bbaf694","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T13:09:21Z","timestamp":1765458561000},"source":"Crossref","is-referenced-by-count":2,"title":["Identification of cancer mini-drivers by deciphering selective landscape in the cancer genome"],"prefix":"10.1093","volume":"27","author":[{"given":"Xunuo","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Advanced Drug Delivery and Release Systems & Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research , College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd, Xihu District, Hangzhou, Zhejiang 310058,","place":["P.R. 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