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This assessment was performed through simulations and case studies involving two epigenome-wide association studies (EWAS) on rheumatoid arthritis and major depressive disorder. Our evaluation provided insights into the strengths and limitations of each model. The results revealed that the models varied in performance across different metrics, sample sizes, and computational efficiency. Additionally, we proposed integrating the results from these models using the minimum p-value ($minpv$) and average p-value ($avepv$) approaches. Our findings demonstrated that these aggregation methods significantly improved performance in identifying cell-type-specific differential methylation CpGs.<\/jats:p>","DOI":"10.1093\/bib\/bbaf170","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T13:39:02Z","timestamp":1744810742000},"source":"Crossref","is-referenced-by-count":0,"title":["A systematic evaluation of cell-type-specific differential methylation analysis in bulk tissue"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1608-0714","authenticated-orcid":false,"given":"Shuo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Applied Mathematics and Statistics, Stony Brook University , Nicolls Road, 11794, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7861-916X","authenticated-orcid":false,"given":"Pei Fen","family":"Kuan","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics and Statistics, Stony Brook University , Nicolls Road, 11794, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"2025041609385943200_ref1","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nature05913","article-title":"Perceptions of epigenetics","volume":"447","author":"Bird","year":"2007","journal-title":"Nature"},{"key":"2025041609385943200_ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-8935-6-4","article-title":"Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array","volume":"6","author":"Price","year":"2013","journal-title":"Epigenetics 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