Toward trustable use of machine learning models of variant effects in the clinic

Mafalda Dias

doi:10.1016/j.ajhg.2024.10.011

Toward trustable use of machine learning models of variant effects in the clinic

2024-12-01

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DOI：10.1016/j.ajhg.2024.10.011

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There has been considerable progress in building models to predict the effect of missense substitutions in protein-coding genes, fueled in large part by progress in applying deep learning methods to sequence data. These models have the potential to enable clinical variant annotation on a large scale and hence increase the impact of patient sequencing in guiding diagnosis and treatment. To realize this potential, it is essential to provide reliable assessments of model performance, scope of applicability, and robustness. As a response to this bration of in-silico predictions in the context of guidelines for variant annotation. While this work marks an important step forward, the strategy presented still has important limitations. We propose core principles and recommendations to overcome these limitations that can enable both more reliable and more impactful use of variant effect prediction models in the future.

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Toward trustable use of machine learning models of variant effects in the clinic

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