Differential quantification of alternative splicing events on spliced pangenome graphs.

Abstract

Pangenomes are becoming a powerful framework to perform many bioinformatics analyses taking into account the genetic variability of a population, thus reducing the bias introduced by a single reference genome. With the wider diffusion of pangenomes, integrating genetic variability with transcriptome diversity is becoming a natural extension that demands specific methods for its exploration. In this work, we extend the notion of spliced pangenomes to that of annotated spliced pangenomes; this allows us to introduce a formal definition of Alternative Splicing (AS) events on a graph structure. To investigate the usage of graph pangenomes for the quantification of AS events across conditions, we developed pantas, the first pangenomic method for the detection and differential analysis of AS events from short RNA-Seq reads. A comparison with state-of-the-art linear reference-based approaches proves that pantas achieves competitive accuracy, making spliced pangenomes effective for conducting AS events quantification and opening future directions for the analysis of population-based transcriptomes.