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Updated: Oct 3, 2025

Three Differential Expression Analysis Methods for RNA Sequencing: limma, EdgeR, DESeq2
Published on: September 18, 2021
Transcriptome analysis method based on differential distribution evaluation
Yiwei Meng1,2, Yanhong Huang3,4, Xiao Chang5
1State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
Abstract:
Identifying differential genes over conditions provides insights into the mechanisms of biological processes and disease progression. Here we present an approach, the Kullback-Leibler divergence-based differential distribution (klDD), which provides a flexible framework for quantifying changes in higher-order statistical information of genes including mean and variance/covariation. The method can well detect subtle differences in gene expression distributions in contrast to mean or variance shifts of the existing methods. In addition to effectively identifying informational genes in terms of differential distribution, klDD can be directly applied to cancer subtyping, single-cell clustering and disease early-warning detection, which were all validated by various benchmark datasets.

