Machine learning approaches for predicting the small molecule-miRNA associations: a comprehensive review.

MicroRNAs (miRNAs) are evolutionarily conserved small regulatory elements that are ubiquitous in cells and are found to be abnormally expressed during the onset and progression of several human diseases. miRNAs are increasingly recognized as potential diagnostic and therapeutic targets that could be inhibited by small molecules (SMs). The knowledge of SM-miRNA associations (SMAs) is sparse, mainly because of the dynamic and less predictable 3D structures of miRNAs that restrict the high-throughput screening of SMs. Toward augmenting the costly and laborious experiments determining the SM-miRNA interactions, machine learning (ML) has emerged as a cost-effective and efficient platform. In this article, various aspects associated with the ML-guided predictions of SMAs are thoroughly reviewed. Firstly, a detailed account of the SMA data resources useful for algorithms training is provided, followed by an elaboration of various feature extraction methods and similarity measures utilized on SMs and miRNAs. Subsequent to a summary of the ML algorithms basics and a brief description of the performance measures, an exhaustive census of all the 32 ML-based SMA prediction methods developed so far is outlined. Distinctive features of these methods have been described by classifying them into six broad categories, namely, classical ML, deep learning, matrix factorization, network propagation, graph learning, and ensemble learning methods. Trend analyses are performed to investigate the patterns in ML algorithms usage and performance achievement in SMA prediction. Outlining key principles behind the up-to-date methodologies and comparing their accomplishments, this review offers valuable insights into critical areas for future research in ML-based SMA prediction.