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Statistical approaches address conventional small sample sizes and implement empirical Bayes or non\u2010parametric tests, but frequently produce different conclusions. Increasing sample sizes enable proposal of alternative DE paradigms. Here we develop RoPE, which uses a data\u2010driven adjustment for variation and a robust profile likelihood ratio DE test. Simulation studies show RoPE can have improved performance over existing tools as sample size increases and has the most reliable control of error rates. Application of RoPE demonstrates that an active\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    infection downregulates the\n                    <jats:italic>SLC9A3<\/jats:italic>\n                    Cystic Fibrosis modifier gene.\n                  <\/jats:p>","DOI":"10.1002\/gepi.22526","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T08:38:35Z","timestamp":1681288715000},"page":"379-393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RoPE: A robust profile likelihood method for differential gene expression analysis"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0926-1357","authenticated-orcid":false,"given":"Lehang","family":"Zhong","sequence":"first","affiliation":[{"name":"Division of Biostatistics, Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada"},{"name":"Program in Genetics and Genome Biology The Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-9740","authenticated-orcid":false,"given":"Lisa J.","family":"Strug","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada"},{"name":"Program in Genetics and Genome Biology The Hospital for Sick Children Toronto Ontario Canada"},{"name":"Departments of Statistical Sciences and Computer Science University of Toronto Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.03.017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1466-5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2759"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1471082X17715718"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8987.2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","unstructured":"Choi L.(2011) \u2018ProfileLikelihood: Profile likelihood for a parameter in commonly used statistical models\u2019. 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