Modeling gene interactions in polygenic prediction via geometric deep learning.

ABSTRACT: Polygenic risk score (PRS) is a widely used approach for predicting individuals' genetic risk of complex diseases, playing a pivotal role in advancing precision medicine. Traditional PRS methods, predominantly following a linear structure, often fall short in capturing the intricate relationships between genotype and phenotype. In this study, we present PRS-Net, an interpretable geometric deep learning-based framework that effectively models the nonlinearity of biological systems for enhanced disease prediction and biological discovery. PRS-Net begins by deconvoluting the genome-wide PRS at the single-gene resolution and then explicitly encapsulates gene-gene interactions leveraging a graph neural network (GNN) for genetic risk prediction, enabling a systematic characterization of molecula

SUBMITTER: Li H 

PROVIDER: S-EPMC11789630 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature