GenRiskPro: A Comprehensive Whole-Genome Sequencing Analysis Platform for Clinical and Wellness Applications

Area of Science:

• Genomics and Bioinformatics
• Clinical Decision Support Systems
• Precision Medicine

Background:

• Translating whole-genome sequencing (WGS) data into actionable clinical insights remains a significant challenge.
• Existing platforms often lack integrated pipelines for both rare and common variant analysis.
• Efficient genomic variant reporting for clinicians and patients is crucial for personalized healthcare.

Purpose of the Study:

• To introduce GenRiskPro, a novel clinical decision-support and research platform for automated WGS analysis.
• To demonstrate the platform's capability in integrating rare and common variant prioritization for comprehensive genomic insights.
• To facilitate precision wellness by delivering user-friendly, actionable genomic findings.

Main Methods:

• Development of a unified WGS variant calling, annotation, prioritization, and reporting pipeline.
• Integration of an in-house database for rare and common variant analysis.
• Utilized LongevityCloud for clinician review and patient reporting via web portal and AI-integrated mobile app.
• Case studies on Turkish (n=275) and Swedish (n=101) WGS data.

Main Results:

• A 1.82% positive rate for actionable findings per ACMG secondary findings guidelines using predefined gene panels.
• Successful diagnosis of cases including muscular dystrophy and microcephaly through phenotype-driven analysis.
• Identification of potentially misclassified pathogenic variants via cohort-level ClinVar reassessment.
• Discovery of rare variant enrichment (ABCA4 in TR, SMPD1 in SW) and population-specific carrier differences in trait-associated SNPs and PGx variants.

Conclusions:

• GenRiskPro effectively automates WGS analysis, providing rapid, user-friendly genomic insights for clinical decision support and research.
• The platform's integrated approach enhances the identification of actionable findings and facilitates precision wellness.
• GenRiskPro fosters collaboration among stakeholders, accelerating the translation of genomic discoveries into personalized healthcare.