Plenty of microRNAs (miRNAs) were discovered at a rapid pace in plants, green algae, viruses and animals. As one of the most important components in the cell, miRNAs play a growing important role in various essential and important biological processes. For the recent few decades, amounts of experimental methods and computational models have been designed and implemented to identify novel miRNA–disease associations. In this review, the functions of miRNAs, miRNA–target interactions, miRNA–disease associations and some important publicly available miRNA-related databases were discussed in detail. Specially, considering the important fact that an increasing number of miRNA–disease associations have been experimentally confirmed, we selected five important miRNA-related human diseases and five crucial disease-related miRNAs and provided corresponding introductions. Identifying disease-related miRNAs has become an important goal of biomedical research, which will accelerate the understanding of disease pathogenesis at the molecular level and molecular tools design for disease diagnosis, treatment and prevention. Computational models have become an important means for novel miRNA–disease association identification, which could select the most promising miRNA–disease pairs for experimental validation and significantly reduce the time and cost of the biological experiments. Here, we reviewed 20 state-of-the-art computational models of predicting miRNA–disease associations from different perspectives. Finally, we summarized four important factors for the difficulties of predicting potential disease-related miRNAs, the framework of constructing powerful computational models to predict potential miRNA–disease associations including five feasible and important research schemas, and future directions for further development of computational models.

LncRNAs have attracted lots of attentions from researchers worldwide in recent decades. With the rapid advances in both experimental technology and computational prediction algorithm, thousands of lncRNA have been identified in eukaryotic organisms ranging from nematodes to humans in the past few years. More and more research evidences have indicated that lncRNAs are involved in almost the whole life cycle of cells through different mechanisms and play important roles in many critical biological processes. Therefore, it is not surprising that the mutations and dysregulations of lncRNAs would contribute to the development of various human complex diseases. In this review, we first made a brief introduction about the functions of lncRNAs, five important lncRNA-related diseases, five critical disease-related lncRNAs and some important publicly available lncRNA-related databases about sequence, expression, function, etc. Nowadays, only a limited number of lncRNAs have been experimentally reported to be related to human diseases. Therefore, analyzing available lncRNA–disease associations and predicting potential human lncRNA–disease associations have become important tasks of bioinformatics, which would benefit human complex diseases mechanism understanding at lncRNA level, disease biomarker detection and disease diagnosis, treatment, prognosis and prevention. Furthermore, we introduced some state-of-the-art computational models, which could be effectively used to identify disease-related lncRNAs on a large scale and select the most promising disease-related lncRNAs for experimental validation. We also analyzed the limitations of these models and discussed the future directions of developing computational models for lncRNA research.

In the recent few years, an increasing number of studies have shown that microRNAs (miRNAs) play critical roles in many fundamental and important biological processes. As one of pathogenetic factors, the molecular mechanisms underlying human complex diseases still have not been completely understood from the perspective of miRNA. Predicting potential miRNA-disease associations makes important contributions to understanding the pathogenesis of diseases, developing new drugs, and formulating individualized diagnosis and treatment for diverse human complex diseases. Instead of only depending on expensive and time-consuming biological experiments, computational prediction models are effective by predicting potential miRNA-disease associations, prioritizing candidate miRNAs for the investigated diseases, and selecting those miRNAs with higher association probabilities for further experimental validation. In this study, Path-Based MiRNA-Disease Association (PBMDA) prediction model was proposed by integrating known human miRNA-disease associations, miRNA functional similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity for miRNAs and diseases. This model constructed a heterogeneous graph consisting of three interlinked sub-graphs and further adopted depth-first search algorithm to infer potential miRNA-disease associations. As a result, PBMDA achieved reliable performance in the frameworks of both local and global LOOCV (AUCs of 0.8341 and 0.9169, respectively) and 5-fold cross validation (average AUC of 0.9172). In the cases studies of three important human diseases, 88% (Esophageal Neoplasms), 88% (Kidney Neoplasms) and 90% (Colon Neoplasms) of top-50 predicted miRNAs have been manually confirmed by previous experimental reports from literatures. Through the comparison performance between PBMDA and other previous models in case studies, the reliable performance also demonstrates that PBMDA could serve as a powerful computational tool to accelerate the identification of disease-miRNA associations. Identification of miRNA-disease associations is considered as a key way for the development of pathology, diagnose and therapy. Computational prediction models contribute to discovering the underlying disease-related miRNAs on a large scale. Based on the assumption that functionally related miRNAs tend to be involved in phenotypically similar disease and vice versa, the model of PBMDA was developed to prioritize the underlying miRNA-disease associations by adopting a special depth-first search algorithm in a heterogeneous graph, which was composed of known miRNA-disease association network, miRNA similarity network, and disease similarity network. Through leave-one-out cross validation and 5-fold cross validation, the promising results demonstrated the effectiveness of the proposed model. We further implemented the case studies of three important human complex diseases, 88%, 88% and 90% of top-50 predicted miRNA-disease associations have been manually confirmed based on recent experimental reports. It is anticipated that PBMDA could prioritize the most potential miRNA-disease associations on a large scale for advancing the progress of biological experiment validation in the future, which could further contribute to the understanding of complex disease mechanisms.

Increasing evidences have indicated that microRNAs (miRNAs) are functionally associated with the development and progression of various complex human diseases. However, the roles of miRNAs in multiple biological processes or various diseases and their underlying molecular mechanisms still have not been fully understood yet. Predicting potential miRNA-disease associations by integrating various heterogeneous biological datasets is of great significance to the biomedical research. Computational methods could obtain potential miRNA-disease associations in a short time, which significantly reduce the experimental time and cost. Considering the limitations in previous computational methods, we developed the model of Within and Between Score for MiRNA-Disease Association prediction (WBSMDA) to predict potential miRNAs associated with various complex diseases. WBSMDA could be applied to the diseases without any known related miRNAs. The AUC of 0.8031 based on Leave-one-out cross validation has demonstrated its reliable performance. WBSMDA was further applied to Colon Neoplasms, Prostate Neoplasms and Lymphoma for the identification of their potential related miRNAs. As a result, 90%, 84% and 80% of predicted miRNA-disease pairs in the top 50 prediction list for these three diseases have been confirmed by recent experimental literatures, respectively. It is anticipated that WBSMDA would be a useful resource for potential miRNA-disease association identification.

Nonnegative matrix factorization (NMF)-based models possess fine representativeness of a target matrix, which is critically important in collaborative filtering (CF)-based recommender systems. However, current NMF-based CF recommenders suffer from the problem of high computational and storage complexity, as well as slow convergence rate, which prevents them from industrial usage in context of big data. To address these issues, this paper proposes an alternating direction method (ADM)-based nonnegative latent factor (ANLF) model. The main idea is to implement the ADM-based optimization with regard to each single feature, to obtain high convergence rate as well as low complexity. Both computational and storage costs of ANLF are linear with the size of given data in the target matrix, which ensures high efficiency when dealing with extremely sparse matrices usually seen in CF problems. As demonstrated by the experiments on large, real data sets, ANLF also ensures fast convergence and high prediction accuracy, as well as the maintenance of nonnegativity constraints. Moreover, it is simple and easy to implement for real applications of learning systems.

Protein-protein interactions (PPIs) play crucial roles in the execution of various cellular processes and form the basis of biological mechanisms. Although large amount of PPIs data for different species has been generated by high-throughput experimental techniques, current PPI pairs obtained with experimental methods cover only a fraction of the complete PPI networks, and further, the experimental methods for identifying PPIs are both time-consuming and expensive. Hence, it is urgent and challenging to develop automated computational methods to efficiently and accurately predict PPIs.