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As the cost of sequencing DNA decreases, the number of DGE datasets is expected to grow dramatically.<\/jats:p><jats:p>Various tests of differential expression have been proposed for replicated DGE data using binomial, Poisson, negative binomial or pseudo-likelihood (PL) models for the counts, but none of the these are usable when the number of replicates is very small.<\/jats:p><jats:p>Results: We develop tests using the negative binomial distribution to model overdispersion relative to the Poisson, and use conditional weighted likelihood to moderate the level of overdispersion across genes. Not only is our strategy applicable even with the smallest number of libraries, but it also proves to be more powerful than previous strategies when more libraries are available. The methodology is equally applicable to other counting technologies, such as proteomic spectral counts.<\/jats:p><jats:p>Availability: An R package can be accessed from http:\/\/bioinf.wehi.edu.au\/resources\/<\/jats:p><jats:p>Contact: \u00a0smyth@wehi.edu.au<\/jats:p><jats:p>Supplementary information: \u00a0http:\/\/bioinf.wehi.edu.au\/resources\/<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm453","type":"journal-article","created":{"date-parts":[[2007,9,20]],"date-time":"2007-09-20T00:24:46Z","timestamp":1190247886000},"page":"2881-2887","source":"Crossref","is-referenced-by-count":742,"title":["Moderated statistical tests for assessing differences in tag abundance"],"prefix":"10.1093","volume":"23","author":[{"given":"Mark D.","family":"Robinson","sequence":"first","affiliation":[{"name":"1 Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010 and 2Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia"},{"name":"1 Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010 and 2Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia"}]},{"given":"Gordon K.","family":"Smyth","sequence":"additional","affiliation":[{"name":"1 Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010 and 2Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia"}]}],"member":"286","published-online":{"date-parts":[[2007,9,19]]},"reference":[{"key":"2023041107265303200_","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1038\/sj.onc.1209279","article-title":"Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloroteinase-10 are novel prognostic factors in patients with gastric cancer","volume":"25","author":"Aung","year":"2006","journal-title":"Oncogene"},{"key":"2023041107265303200_","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1093\/bioinformatics\/btg173","article-title":"Differential expression in SAGE: accounting for normal between-library variation","volume":"19","author":"Baggerly","year":"2003","journal-title":"BMC Bioinformatics"},{"key":"2023041107265303200_","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/1471-2105-5-144","article-title":"Overdispersed logistic regression for SAGE: modelling multiple groups and covariates","volume":"5","author":"Baggerly","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"2023041107265303200_","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1198\/106186002317375677","article-title":"Bayesian inference for the negative binomial distribution via polynomial expansions","volume":"11","author":"Bradlow","year":"2002","journal-title":"J. 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