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Gyasu Bajracharya on Muck Rack

Gyasu Bajracharya

As seen in: BioRxiv
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Articles

Fine-tuning protein language models on human spatial constraint improves variant effect prediction by reducing wild-type sequence bias

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By John Anthony Capra, Gyasu Bajracharya
| BioRxiv
Abstract Protein language models (PLMs) achieve state-of-the-art performance in predicting effects of missense variants, yet they do not explicitly consider variation within the human population. Here, we introduce Human Spatial Constraint (HuSC), a framework for quantifying intraspecies constraint on missense variants that integrates population-scale human genetic variation with 3D protein structures. We then fine-tune PLMs on HuSC scores.
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