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Although many harmonization methods exist, prior evaluations have focused mainly on differential expression analysis, leaving the impact on subgroup discovery understudied. We present a framework for evaluating harmonization in the context of sample clustering, which integrates AI-augmented datasets, statistical evaluation pipelines, and accessible software tools, enabling systematic comparisons across diverse signal-to-artifact ratios and cluster composition settings. Using this framework, we show that harmonization can, often partially, restore clustering accuracy lost to artifacts, especially at moderate signal-to-artifact ratios, with the level of gains depending on the specific harmonization method, the paired clustering technique, and the cluster composition setting. We further confirm these findings by analyzing reconstructed cohorts from The Cancer Genome Atlas breast cancer microRNA sequencing data. Collectively, the results underscore the need for tailored harmonization to support reliable subgroup discovery and highlight the broader importance of context-specific workflows in translational genomics.<\/jats:p>","DOI":"10.64898\/2026.08.09.743718","type":"posted-content","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:35:11Z","timestamp":1786743311000},"source":"Crossref","is-referenced-by-count":0,"title":["Contextual Evaluation of MicroRNA Sequencing Data Harmonization: Performance in Sample Clustering"],"prefix":"10.64898","author":[{"given":"Jian","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Statistics, School of Public Health, Chongqing Medical University, Chongqing, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"D\u00fcren","sequence":"additional","affiliation":[{"name":"Department of Mathematical Statistics, Ruhr-University Bochum, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States"},{"name":"Department of Statistics, The University of California, Davis, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States"},{"name":"Department of Statistics, University of Iowa, Iowa City, IA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhui","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States"},{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States"},{"name":"Department of Industrial Engineering and Operations Research, Columbia University, New York, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Mathematical Sciences, Nanyang Technological University, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Xuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081804350734000_2026.08.09.743718v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"2026081804350734000_2026.08.09.743718v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02871"},{"key":"2026081804350734000_2026.08.09.743718v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209914"},{"key":"2026081804350734000_2026.08.09.743718v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz016"},{"key":"2026081804350734000_2026.08.09.743718v1.5","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-94"},{"key":"2026081804350734000_2026.08.09.743718v1.6","doi-asserted-by":"crossref","unstructured":"Sahoo, O. 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