Machine Learning Prediction of Non-Coding Variant Impact in Cell-Class-Specific Human Retinal <i>Cis</i>-Regulatory Elements.

ABSTRACT: Non-coding variants in cis-regulatory elements such as promoters and enhancers contribute to inherited retinal diseases (IRDs), however, characterizing the functional impact of most regulatory variants remains challenging. To improve identification of variants of interest, we implemented machine learning using a gapped k-mer support vector machine approach trained on single nucleus ATAC-seq data from specific cell classes of the adult and developing human retina. We developed 18 distinct ML models to predict the impact of non-coding variants on 39,437 cell-class-specific regulatory elements. These models demonstrate accuracy over 90% and a high degree of cell class specificity. Variant Impact Prediction (VIP) scores highlight specific sequences within candidate CREs, including putative tra

SUBMITTER: VandenBosch LS 

PROVIDER: S-EPMC11888276 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature