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Accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis


The regulation of mRNA controls both overall gene expression as well as the distribution of mRNA isoforms encoded by the gene. Current algorithmic approaches focus on characterization of significant differential expression or alternative splicing events or isoform distribution without integrating both events.

Here, we present Hierarchical Bayesian Analysis of Differential Expression and ALternative SPlicing (HBA-DEALS), which simultaneously characterizes differential expression and splicing in cohorts.

HBA-DEALS attains state of the art or better performance for both expression and splicing, and allows genes to be characterized as having differential gene expression (DGE), differential alternative splicing (DAST), both, or neither. Based on an analysis of Genotype-Tissue Expression (GTEx) data we demonstrate the existence of sets of genes that show predominant DGE or DAST across a comparison of 20 tissue types, and show that these sets have pervasive differences with respect to gene structure, function, membership in protein complexes, and promoter architecture.

Authors: Guy Karlebach, Peter Hansen, Diogo F.T. Veiga, Robin Steinhaus, Daniel Danis, Sheng Li, Olga Anczukow, Peter N. Robinson

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