Differential quantification of alternative splicing events on spliced pangenome graphs

Abstract

AbstractPangenomes are becoming a powerful frameworks 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 ofannotated 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 developedpantas, the first pangenomic method for differential analysis of AS events. A comparison with state-of-the-art linear reference-based approaches proves thatpantasachieves competitive accuracy, making spliced pangenomes effective for conducting AS events quantification and opening future directions for the analysis of population-based transcriptomes.pantasis open-source and freely available at github.com/algolab/pantas.