Barfield, S. | Search bioRxiv

bioRxiv2025

Evaluating a Standard Benchmark for Gene Prioritization: The InheriNext(R) Algorithm's Integration of Genomic and Phenotypic Information

This study presents a comprehensive benchmark analysis of InheriNext(R), a domain-specific, AI-powered tool designed for phenotype-driven pathogenic variant prioritization. For this study, 7,244 whole exome test cases were generated using phenotype and genotype data from Phenopackets, along with pools of variants from healthy individuals to serve as genomic backgrounds. Performance was evaluated across diverse testing scenarios and compared against four established tools. The results show InheriNext(R) achieving a 98.6% sensitivity in identifying pathogenic variants and consistent performance across diverse tests for variant types, phenotype counts, and disease groups--supporting the robustness and adaptability of its methodology. Sharing these benchmarking results and samples is intended to drive progress by assisting clinicians and researchers in evaluating interpretation tools and identifying areas for improvement.

genomics↗

bioRxiv2020

Co-recruitment of relatives in a broadcast-spawning coral (Acropora hyacinthus) facilitates emergence of an inbred, genetically distinct group within a panmictic population

Many broadly-dispersing marine taxa are species-rich, show genetic heterogeneity on small spatial scales, and are locally adapted to their environmental conditions. How such genetic subdivisions can emerge despite the potential for high gene flow continues to be the major paradox of evolution in the sea. One understudied process potentially contributing to genetic structuring in marine populations is variation in larval recruitment. Here, we report an unusual recruitment pattern in the broadcast-spawning coral species Acropora hyacinthus on Yap Island, Micronesia. Reduced representation genotyping of 275 individuals of varying size classes on this isolated reef system demonstrated general island-wide panmixia but also identified a genetically divergent group of juvenile corals at one out of the four sites sampled, showing elevated inbreeding and relatedness, including two pairs of siblings. Notably, adult corals as well as the majority of juveniles at the same site belong to the panmictic gene pool, suggesting that representatives of the inbred lineage of juveniles co-recruited and may be partially reproductively isolated from the rest of the island population. Reproductive isolation is suggested by the discovery of distinct genomic regions of greatly reduced genetic diversity in the inbred lineage, encompassing genes involved in sperm-egg recognition and fertilization that may serve as reproductive barrier loci. We propose that co-recruitment of genetic relatives via cohesive dispersal, a process that was previously unrecognized in broadcast-spawning corals, can generate familial genetic structure and might be important for the emergence of genetically distinct, locally adapted ecomorphs and cryptic species.

evolutionary biology↗