Clustering of mRNA-Seq data based on alternative splicing patterns

Sequencing of messenger RNA (mRNA) can provide estimates of the levels of individual isoforms within the cell. It remains to adapt many standard statistical methods commonly used for analyzing gene expression levels to take advantage of this additional information. One novel question is whether we can find clusters of samples that are distinguished not by their gene expression but by their isoform usage. We propose a novel approach for clustering mRNA-Seq data that identifies such clusters. We show via simulation that our methods are more sensitive to finding clusters based on isoform usage than standard clustering techniques. We demonstrate its performance by finding a technical artifact that resulted in different batches having different isoform usage patterns, and illustrate its usage on several The Cancer Genome Atlas datasets.