Simultaneous Structural Variation Discovery in Multiple Paired-End Sequenced Genomes

As whole genome shotgun sequencing (WGSS) becomes more accessible using high-throughput sequencing technologies, undertaking comparative studies among different individuals (based on population, race, or genetic disease) is the next logical step. In this paper, we propose a paradigm shift in variation comparative studies (specifically structural variation) away from the conventional two step approach of i) independent structural variation discovery and ii) pairwise comparison of structural variation to a simultaneous structural variation discovery framework in multiple genomes. For the first time, we formally introduce the maximum parsimony-based simultaneous structural variation discovery in multiple genomes problem and provide an asymptotically tight approximate algorithm. Tests of the proposed framework on the genomes of the mother-father-child trio sequenced by Illumina and comparisons between the structural variations predicted with known variations in these genomes show that the conventional strategy works poorly in providing meaningful biological results through comparative analysis. For instance, the traditional framework predicts an extremely high number of de novo variations in the child in comparison to his parents. Our proposed framework not only significantly reduces the number of incorrect de novo variations for the same number of total variations but also predicts more known true positive variations. ∗Corresponding authors: [email protected], [email protected]