Comparison of missing data handling methods for variant pathogenicity predictors

: Särkkä, Mikko; Myöhänen, Sami; Marinov, Kaloyan; Saarinen, Inka; Lahti, Leo; Fortino, Vittorio; Paananen, Jussi

Publisher: Oxford University Press (OUP)

: 2025

NAR Genomics and Bioinformatics: Nucleic Acids Research Genomics and Bioinformatics

: lqaf133

: 7

: 4

: 2631-9268

DOI: https://doi.org/10.1093/nargab/lqaf133

: https://doi.org/10.1093/nargab/lqaf133

: https://research.utu.fi/converis/portal/detail/Publication/504736398

Modern clinical genetic tests utilize next-generation sequencing (NGS) approaches to comprehensively analyze genetic variants from patients. Out of millions of variants, clinically relevant variants that match the patient's phenotype must be identified accurately and rapidly. As manual evaluation is not a feasible option for meeting the speed and volume requirements of clinical genetic testing, automated solutions are needed. Various machine learning (ML), artificial intelligence (AI), and in silico variant pathogenicity predictors have been developed to solve this challenge. These solutions rely on comprehensive data and struggle with the sparse genetic annotations. Therefore, careful treatment of missing data is necessary, and the selected methods may have a huge impact on the accuracy, reliability, speed and associated computational costs. We present an open-source framework called AMISS that can be used to evaluate performance of different methods for handling missing genetic variant data in the context of variant pathogenicity prediction. Using AMISS, we evaluated 14 methods for handling missing values. The performance of these methods varied substantially in terms of precision, computational costs, and other attributes. Overall, simpler imputation methods and specifically mean imputation performed best.

lqaf133.pdf

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