MIRACN: a residual convolutional neural network for predicting cell line specific functional regulatory variants.

Abstract

In post-genome-wide association study era, interpretation of noncoding variants remains a significant challenge due to their complexity and the limited understanding of their functions. Here, we developed MIRACN, a novel residual convolutional neural network designed to predict cell line-specific functional regulatory variants. By utilizing a substantial dataset from massively parallel reporter assays (MPRAs) and employing a multitask learning strategy, MIRACN was trained across seven distinct cell lines, attaining superior performance compared to existing methods, especially in predicting cell type specificity. Comparative evaluations on an independent MPRA test dataset demonstrated that MIRACN not only outperformed in identifying regulatory variants but also provided valuable insights into their cellular context-specific regulatory mechanisms. MIRACN is capable of not only providing scores for functional variants but also pinpointing the specific cell line in which these variants display their function. This enhancement has improved the resolution of current research on the functionality of noncoding variants and has paved the way for more precise diagnostic and therapeutic strategies.