Evaluation of methods for the inference of ancestral recombination graphs

The ancestral recombination graph (ARG) is a structure that describes the joint genealogies of sampled DNA sequences along the genome. Recent computational methods have made impressive progress towards scalably estimating whole-genome genealogies. In addition to inferring the ARG, some of these methods can also provide ARGs sampled from a defined posterior distribution. Obtaining good samples of ARGs is crucial for quantifying statistical uncertainty and for estimating population genetic parameters such as effective population size, mutation rate, and allele age. Here, we use simulations to benchmark three popular ARG inference programs: ARGweaver, Relate, and tsdate. We use neutral coalescent simulations to 1) compare the true coalescence times to the inferred times at each locus; 2) compare the distribution of coalescence times across all loci to the expected exponential distribution; 3) evaluate whether the sampled coalescence times have the properties expected of a valid posterior distribution. We find that inferred coalescence times at each locus are more accurate in ARGweaver and Relate than in tsdate. However, all three methods tend to overestimate small coalescence times and underestimate large ones. Lastly, the posterior distribution of ARGweaver is closer to the expected posterior distribution than Relate’s, but this higher accuracy comes at a substantial trade-off in scalability. The best choice of method will depend on the number and length of input sequences and on the goal of downstream analyses, and we provide guidelines for the best practices. ### Competing Interest Statement The authors have declared no competing interest.