Variant effects on protein-protein interactions: methods, models and diseases

2025/07/23 by Larsen-Ledet, Sven, Panfilova, Aleksandra, Stein, Amelie
#Biomolecules (q-bio.BM) #FOS: Biological sciences #Molecular Networks (q-bio.MN)

paper · doi:10.48550/arxiv.2507.17446

Abstract

Advances in sequencing have revealed that each individual carries about 10,000 missense variants. For the vast majority, we do not know what the functional consequences - if any - will be. Further, mechanistic insight, such as structural details, would be immensely helpful in development of therapeutic approaches. Here we review recent developments in experimental and computational techniques aimed to assess the impact of variants on protein-protein interactions, including limitations and upcoming challenges.

Related

• Fine-tuning the ESM2 protein language model to understand the functional impact of missense variants
• Genome-wide prediction of disease variant effects with a deep protein language model
• Decoding molecular mechanisms for loss-of-function variants in the human proteome
• The Impact of Genomic Variation on Function (IGVF) Consortium
• Fine-tuning protein language models to understand the functional impact of missense variants