Representing and decomposing genomic structural variants as balanced integer flows on sequence graphs

TL;DR

This paper introduces a comprehensive mathematical model for genomic structural variants, capturing complex rearrangements and copy number changes, and provides methods to sample possible evolutionary histories explaining genomic differences.

Contribution

It presents a novel model of structural variation as balanced integer flows on sequence graphs, enabling ergodic sampling of evolutionary histories.

Findings

Model encompasses balanced rearrangements and CNVs.

Allows ergodic sampling of evolutionary histories.

Facilitates analysis of complex genomic variations.

Abstract

The study of genomic variation has provided key insights into the functional role of mutations. Predominantly, studies have focused on single nucleotide variants (SNV), which are relatively easy to detect and can be described with rich mathematical models. However, it has been observed that genomes are highly plastic, and that whole regions can be moved, removed or duplicated in bulk. These structural variants (SV) have been shown to have significant impact on the phenotype, but their study has been held back by the combinatorial complexity of the underlying models. We describe here a general model of structural variation that encompasses both balanced rearrangements and arbitrary copy-numbers variants (CNV). In this model, we show that the space of possible evolutionary histories that explain the structural differences between any two genomes can be sampled ergodically.