Abstract:
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The benefit of integrating batches of genomic data to increase statistical power is often hindered by batch effects, unwanted variation in data caused by differences in technical factors across batches. It is therefore important to effectively address batch effects in genomic data. Many existing methods for batch adjustment assume continuous, bell-shaped Normal distribution for data. However in RNA-Seq studies where data are skewed, over-dispersed counts, this assumption is not appropriate and may lead to erroneous results. Negative binomial regression models have been used in differential expression methods to better describe the properties of counts. We developed a batch effect adjustment algorithm, ComBat-Seq, using a negative binomial regression. We show in realistic simulations and real data that ComBat-Seq adjusted data often yield higher statistical power in differential expression compared to other available methods, especially when batch effect is severe.
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