Simulating population pangenomes under coalescent demographic models with MSpangenome

Abstract

MotivationPangenome variation graphs (PVGs) are increasingly used to represent genomic diversity, yet there is currently no general framework for generating population pangenomes directly from explicit evolutionary histories. Existing simulators typically focus on individual classes of variation and do not integrate these variations within a genealogy-aware framework driven by explicit demographic histories. As a result, evaluating pangenome methods in realistic population-genetic settings remains challenging, and benchmark datasets with known evolutionary ground truth are scarce. ResultsWe present MSpangenome, a genealogy-aware framework that bridges coalescent population genetic simulations and pangenome graph analyses. The pipeline combines ancestry simulation with msprime and a de novo graph construction algorithm to generate PVGs directly from simulated genealogies. By explicitly modeling recombination, demographic history and incomplete lineage sorting, MSpangenome produces structurally complex pangenomes in which nested and overlapping structural variants emerge naturally from the underlying genealogies, while their evolutionary history and graph topology remain known by construction. This provides a general framework for generating realistic population pangenomes and establishing ground-truth datasets for methodological evaluation. We demonstrate its utility by generating population-scale pangenomes and using them as controlled references to benchmark the widely used graph construction tools, PGGB and Minigraph-Cactus. Our analyses reveal contrasting performance regimes across levels of sequence diversity, sample sizes and classes of structural variation, highlighting the value of simulation-based benchmarking for identifying reconstruction errors that are hard to detect using empirical datasets alone. Availability and implementationMSpangenome is implemented in Python, fully containerized, freely available at https://forge.inrae.fr/pangepop/MSpangepop and mirrored at https://github.com/inrae/MSpangepop.