Understanding structure-guided variant effect predictions using 3D convolutional neural networks.

ABSTRACT: Predicting pathogenicity of missense variants in molecular diagnostics remains a challenge despite the available wealth of data, such as evolutionary information, and the wealth of tools to integrate that data. We describe DeepRank-Mut, a configurable framework designed to extract and learn from physicochemically relevant features of amino acids surrounding missense variants in 3D space. For each variant, various atomic and residue-level features are extracted from its structural environment, including sequence conservation scores of the surrounding amino acids, and stored in multi-channel 3D voxel grids which are then used to train a 3D convolutional neural network (3D-CNN). The resultant model gives a probabilistic estimate of whether a given input variant is disease-causing or benign. W

SUBMITTER: Ramakrishnan G 

PROVIDER: S-EPMC10354367 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature