Efficient identification of de novo mutations in family trios: a consensus-based informatic approach.

ABSTRACT: Accurate identification of de novo variants (DNVs) remains challenging despite advances in sequencing technologies, often requiring ad hoc filters and manual inspection. Here, we explored a purely informatic, consensus-based approach for identifying DNVs in proband-parent trios using short-read genome sequencing data. We evaluated variant calls generated by three sequence analysis pipelines-GATK HaplotypeCaller, DeepTrio, and Velsera GRAF-and examined the assumption that a requirement of consensus can serve as an effective filter for high-quality DNVs. Comparison with a highly accurate DNV set, validated previously by manual inspection and Sanger sequencing, demonstrated that consensus filtering, followed by a force-calling procedure, effectively removed false-positive calls, achieving 98.

SUBMITTER: Shadrina M 

PROVIDER: S-EPMC11953573 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature