Smart variant filtering - A blueprint solution for massively parallel sequencing-based variant analysis.

Brahimllari O, Eloranta S, Georgii-Hemming P, Haider Z, Koch S, Krstic A, Skarp FP, Rosenquist R, Smedby KE, Taylan F, Thorvaldsdottir B, Wirta V, Wästerlid T, Boman M

Health Informatics J 30 (4) 14604582241290725 [2024-10-12; online 2024-10-12]

Massively parallel sequencing helps create new knowledge on genes, variants and their association with disease phenotype. This important technological advancement simultaneously makes clinical decision making, using genomic information for cancer patients, more complex. Currently, identifying actionable pathogenic variants with diagnostic, prognostic, or predictive impact requires substantial manual effort. Objective: The purpose is to design a solution for clinical diagnostics of lymphoma, specifically for systematic variant filtering and interpretation. Methods: A scoping review and demonstrations from specialists serve as a basis for a blueprint of a solution for massively parallel sequencing-based genetic diagnostics. Results: The solution uses machine learning methods to facilitate decision making in the diagnostic process. A validation round of interviews with specialists consolidated the blueprint and anchored it across all relevant expert disciplines. The scoping review identified four components of variant filtering solutions: algorithms and Artificial Intelligence (AI) applications, software, bioinformatics pipelines and variant filtering strategies. The blueprint describes the input, the AI model and the interface for dynamic browsing. Conclusion: An AI-augmented system is designed for predicting pathogenic variants. While such a system can be used to classify identified variants, diagnosticians should still evaluate the classification's accuracy, make corrections when necessary, and ultimately decide which variants are truly pathogenic.

Clinical Genomics Stockholm [Collaborative]

PubMed 39394057

DOI 10.1177/14604582241290725

Crossref 10.1177/14604582241290725