Benchmarking and Optimization of Methods for the Detection of Identity-By-Descent in High-RecombiningPlasmodium falciparum

Abstract

Genomic surveillance is crucial for identifying at-risk populations for targeted malaria control and elimination. Identity-by-descent (IBD) is increasingly being used inPlasmodiumpopulation genomics to estimate genetic relatedness, effective population size (Ne), population structure, and signals of positive selection. Despite its potential, a thorough evaluation of IBD segment detection tools for species with high recombination rates, such asP. falciparum, remains absent. Here, we perform comprehensive benchmarking of IBD callers — probabilistic (hmmIBD, isoRelate), identity-by-state-based (hap-IBD, phased IBD) and others (Refined IBD) — using population genetic simulations tailored for high recombination, and IBD quality metrics at both the IBD segment level and the IBD-based downstream inference level. Our results demonstrate that low marker density per genetic unit, related to high recombination relative to mutation, significantly compromises the accuracy of detected IBD segments. In genomes with high recombination rates resemblingP. falciparum, most IBD callers exhibit high false negative rates for shorter IBD segments, which can be partially mitigated through optimization of IBD caller parameters, especially those related to marker density. Notably, IBD detected with optimized parameters allows for more accurate capture of selection signals and population structure; IBD-based Neinference is very sensitive to IBD detection errors, with IBD called from hmmIBD uniquely providing less biased estimates of Nein this context. Validation with empirical data from the MalariaGEN Pf7 database, representing different transmission settings, corroborates these findings. We conclude that context-specific evaluation and parameter optimization are essential for accurate IBD detection in high-recombining species and recommend hmmIBD for quality-sensitive analysis, such as estimation of Nein these species. Our optimization and high-level benchmarking methods not only improve IBD segment detection in high-recombining genomes but also enhance overall genomic analysis, paving the way for more accurate genomic surveillance and targeted intervention strategies for malaria.