microT-CNN: an avant-garde deep convolutional neural network unravels functional miRNA targets beyond canonical sites.

Abstract

microRNAs (miRNAs) are central post-transcriptional gene expression regulators in healthy and diseased states. Despite decades of effort, deciphering miRNA targets remains challenging, leading to an incomplete miRNA interactome and partially elucidated miRNA functions. Here, we introduce microT-CNN, an avant-garde deep convolutional neural network model that moves the needle by integrating hundreds of tissue-matched (in-)direct experiments from 26 distinct cell types, corresponding to a unique training and evaluation set of >60 000 miRNA binding events and ~30 000 unique miRNA-gene target pairs. The multilayer sequence-based design enables the prediction of both host and virus-encoded miRNA interactions, providing for the first time up to 67% of direct genuine Epstein-Barr virus- and Kaposi's sarcoma-associated herpesvirus-derived miRNA-target pairs corresponding to one out of four binding events of virus-encoded miRNAs. microT-CNN fills the existing gap of the miRNA-target prediction by providing functional targets beyond the canonical sites, including 3' compensatory miRNA pairings, prompting 1.4-fold more validated miRNA binding events compared to other implementations and shedding light on previously unexplored facets of the miRNA interactome.