SCARAP: scalable cross-species comparative genomics of prokaryotes.

Motivation: Much of prokaryotic comparative genomics currently relies on two critical computational tasks: pangenome inference and core genome inference. Pangenome inference involves clustering genes from a set of genomes into gene families, enabling genome-wide association studies and evolutionary history analysis. The core genome represents gene families present in nearly all genomes and is required to infer a high-quality phylogeny. For species-level datasets, fast pangenome inference tools have been developed. However, tools applicable to more diverse datasets are currently slow and scale poorly.

Results: Here, we introduce SCARAP, a program containing three modules for comparative genomics analyses: a fast and scalable pangenome inference module, a direct core genome inference module, and a module for subsampling representative genomes. When benchmarked against existing tools, the SCARAP pan module proved up to an order of magnitude faster with comparable accuracy. The core module was validated by comparing its result against a core genome extracted from a full pangenome. The sample module demonstrated the rapid sampling of genomes with decreasing novelty. Applied to a dataset of over 31 000 Lactobacillales genomes, SCARAP showcased its ability to derive a representative pangenome. Finally, we applied the novel concept of gene fixation frequency to this pangenome, showing that Lactobacillales genes that are prevalent but rarely fixate in species often encode bacteriophage functions.

Availability And Implementation: The SCARAP toolkit is publicly available at https://github.com/swittouck/scarap.