Recommendations for bioinformatics in clinical practice.

Area of Science:

• Genomics
• Bioinformatics
• Clinical Diagnostics

Background:

• Next-generation sequencing (NGS) and whole-genome sequencing (WGS) are increasingly vital in clinical diagnostics.
• Existing guidelines address variant interpretation and lab quality but lack standardized bioinformatics practices.
• Standardization is needed for clinical consensus, accuracy, reproducibility, and comparability in WGS data analysis.

Purpose of the Study:

• To present consensus recommendations for clinical bioinformatics operations in whole-genome sequencing.
• To establish standardized practices for analysis, validation, standardization, accreditation, and core competencies.
• To guide clinical bioinformatics units in producing reliable and reproducible WGS data.

Main Methods:

• Recommendations developed by 13 clinical bioinformatics units from the Nordic Alliance for Clinical Genomics (NACG).
• Focus on clinical practice, including analysis types, testing, validation, standardization, and accreditation.
• Incorporation of core competencies and technical management for clinical bioinformatics.

Main Results:

• Adoption of the hg38 genome build and a standard analysis set, including multiple tools for structural variant (SV) calling.
• Implementation of ISO 15189 standards, clinical-grade HPC, standardized formats, and strict version control for reproducibility.
• Mandatory pipeline documentation, accuracy/reproducibility testing, use of standard truth sets, data integrity verification, and sample identity confirmation.

Conclusions:

• The recommendations offer a consensus framework for standardizing bioinformatics in clinical WGS.
• Provides a practical guide for facilities new to large-scale sequencing diagnostics.
• Serves as a reference for high-volume NGS clinical production facilities.