Evaluating a Standard Benchmark for Gene Prioritization: The InheriNext® Algorithm’s Integration of Genomic and Phenotypic Information

Accurate and efficient variant prioritization is crucial for the interpretation of genomic data in both research and clinical settings. This study presents a comprehensive benchmarking analysis of InheriNext®, a novel tool designed for phenotype-driven pathogenic variant prioritization. We evaluated InheriNext’s performance across diverse testing scenarios, comparing it against four established tools across various variant consequences with varying degrees of phenotype complexity and four major disease groups. 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. Sharing these benchmarking results and samples is intended to drive progress by assisting clinicians and researchers in evaluating interpretation tools and identifying areas of improvements.