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.
MicroRNAs (miRNAs) are small non-coding RNAs (~22 nts) that are considered central post-transcriptional regulators of gene expression and key components in many pathological conditions. Next-Generation Sequencing (NGS) technologies have led to inexpensive, massive data production, revolutionizing every research aspect in the fields of biology and medicine. Particularly, small RNA-Seq (sRNA-Seq) enables small non-coding RNA quantification on a high-throughput scale, providing a closer look into the expression profiles of these crucial regulators within the cell. Here, we present DIANA-microRNA-Analysis-Pipeline (DIANA-mAP), a fully automated computational pipeline that allows the user to perform miRNA NGS data analysis from raw sRNA-Seq libraries to quantification and Differential Expression Analysis in an easy, scalable, efficient, and intuitive way. Emphasis has been given to data pre-processing, an early, critical step in the analysis for the robustness of the final results and conclusions. Through modularity, parallelizability and customization, DIANA-mAP produces high quality expression results, reports and graphs for downstream data mining and statistical analysis. In an extended evaluation, the tool outperforms similar tools providing pre-processing without any adapter knowledge. Closing, DIANA-mAP is a freely available tool. It is available dockerized with no dependency installations or standalone, accompanied by an installation manual through Github.
Only recently, microRNAs (miRNAs) were found to exist in traceable and distinctive amounts in the human circulatory system, bringing forth the intriguing possibility of using them as minimally invasive biomarkers. miRNAs are short non-coding RNAs that act as potent post-transcriptional regulators of gene expression. Extensive studies in cancer and other disease landscapes investigate the protective/pathogenic functions of dysregulated miRNAs, as well as their biomarker potential. A specialized resource amassing experimentally verified, circulating miRNA biomarkers does not exist. We queried the existing literature to identify articles assessing diagnostic/prognostic roles of miRNAs in blood, serum, or plasma samples. Articles were scrutinized in order to exclude instances lacking sufficient experimental documentation or employing no biomarker assessment methods. We incorporated information from more than 200 biomedical articles, annotating crucial meta-information including cohort sizes, inclusion-exclusion criteria, disease/healthy confirmation methods and quantification details. miRNAs and diseases were systematically characterized using reference resources. Our circulating miRNA biomarker collection is provided as an online database, plasmiR. It consists of 1021 entries regarding 251 miRNAs and 112 diseases. More than half of plasmiR’s entries refer to cancerous and neoplastic conditions, 183 of them (32%) describing prognostic associations. plasmiR facilitates smart queries, emphasizing visualization and exploratory modes for all researchers.