Kermut: Composite kernel regression for protein variant effects

Reliable prediction of protein variant effects is crucial for both protein optimization and for advancing biological understanding. For practical use in protein engineering, it is important that we can also provide reliable uncertainty estimates for our predictions, and while prediction accuracy has...

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Bibliographic Details
Published in:arXiv.org 2024-10
Main Authors: Groth, Peter Mørch, Kerrn, Mads Herbert, Olsen, Lars, Salomon, Jesper, Boomsma, Wouter
Format: Article
Language:English
Subjects:
Estimates
Gaussian process
Proteins
Regression models
Uncertainty
Online Access:Get full text
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Summary:Reliable prediction of protein variant effects is crucial for both protein optimization and for advancing biological understanding. For practical use in protein engineering, it is important that we can also provide reliable uncertainty estimates for our predictions, and while prediction accuracy has seen much progress in recent years, uncertainty metrics are rarely reported. We here provide a Gaussian process regression model, Kermut, with a novel composite kernel for modeling mutation similarity, which obtains state-of-the-art performance for supervised protein variant effect prediction while also offering estimates of uncertainty through its posterior. An analysis of the quality of the uncertainty estimates demonstrates that our model provides meaningful levels of overall calibration, but that instance-specific uncertainty calibration remains more challenging.
ISSN:2331-8422