We quantified splicing events (splice junctions, exons, transcripts) by estimating exon inclusion levels, measured as PSI (percent spliced in) scores (14, 18). Clustering samples by PSI scores also largely, although less clearly, recapitulates tissue type. Samples from the brain, not blood, form the primary outgroup (Fig. 1B), which is divided into two groups: A group of 227 samples (from the cerebellum and cortex) forms an independent subcluster (cluster 1), and a smaller group of 97 samples (cluster 2, dominated by the remaining subregions) clusters closer to samples from the rest of the tissues. This is consistent with isoform regulation playing a comparatively larger role in defining cellular specificity in the brain (18, 19). These analyses are extended in Melé et al. (17) to define tissue-specific splicing signatures and to investigate in depth the role of individual variation in splicing.
