Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA-disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA-disease associations, especially for novel lncRNAs, remains challenging. In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA-disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA-disease interactions and functional similarity of diseases based on disease-gene and gene-gene onotology associations. Then, we extract primary feature vectors from Gaussian interaction profile kernel of lncRNAs and functional similarity of diseases by principal component analysis, respectively. For a new lncRNA, we calculate the interaction profile according to the interaction profiles of its neighbors. At last, we complete the association matrix based on the inductive matrix completion framework using the primary feature vectors from the constructed feature matrices. Computational results show that SIMCLDA can effectively predict lncRNA-disease associations with higher accuracy compared with previous methods. Furthermore, case studies show that SIMCLDA can effectively predict candidate lncRNAs for renal cancer, gastric cancer and prostate cancer. https://github.com//bioinfomaticsCSU/SIMCLDA. Supplementary data are available at Bioinformatics online.

Drug repositioning can drastically decrease the cost and duration taken by traditional drug research and development while avoiding the occurrence of unforeseen adverse events. With the rapid advancement of high-throughput technologies and the explosion of various biological data and medical data, computational drug repositioning methods have been appealing and powerful techniques to systematically identify potential drug-target interactions and drug-disease interactions. In this review, we first summarize the available biomedical data and public databases related to drugs, diseases and targets. Then, we discuss existing drug repositioning approaches and group them based on their underlying computational models consisting of classical machine learning, network propagation, matrix factorization and completion, and deep learning based models. We also comprehensively analyze common standard data sets and evaluation metrics used in drug repositioning, and give a brief comparison of various prediction methods on the gold standard data sets. Finally, we conclude our review with a brief discussion on challenges in computational drug repositioning, which includes the problem of reducing the noise and incompleteness of biomedical data, the ensemble of various computation drug repositioning methods, the importance of designing reliable negative samples selection methods, new techniques dealing with the data sparseness problem, the construction of large-scale and comprehensive benchmark data sets and the analysis and explanation of the underlying mechanisms of predicted interactions.

Computational drug repositioning is a cost-effective strategy to identify novel indications for existing drugs. Drug repositioning is often modeled as a recommendation system problem. Taking advantage of the known drug–disease associations, the objective of the recommendation system is to identify new treatments by filling out the unknown entries in the drug–disease association matrix, which is known as matrix completion. Underpinned by the fact that common molecular pathways contribute to many different diseases, the recommendation system assumes that the underlying latent factors determining drug–disease associations are highly correlated. In other words, the drug–disease matrix to be completed is low-rank. Accordingly, matrix completion algorithms efficiently constructing low-rank drug–disease matrix approximations consistent with known associations can be of immense help in discovering the novel drug–disease associations. In this article, we propose to use a bounded nuclear norm regularization (BNNR) method to complete the drug–disease matrix under the low-rank assumption. Instead of strictly fitting the known elements, BNNR is designed to tolerate the noisy drug–drug and disease–disease similarities by incorporating a regularization term to balance the approximation error and the rank properties. Moreover, additional constraints are incorporated into BNNR to ensure that all predicted matrix entry values are within the specific interval. BNNR is carried out on an adjacency matrix of a heterogeneous drug–disease network, which integrates the drug–drug, drug–disease and disease–disease networks. It not only makes full use of available drugs, diseases and their association information, but also is capable of dealing with cold start naturally. Our computational results show that BNNR yields higher drug–disease association prediction accuracy than the current state-of-the-art methods. The most significant gain is in prediction precision measured as the fraction of the positive predictions that are truly positive, which is particularly useful in drug design practice. Cases studies also confirm the accuracy and reliability of BNNR. The code of BNNR is freely available at https://github.com/BioinformaticsCSU/BNNR. Supplementary data are available at Bioinformatics online.

The prediction of drug-target affinities (DTAs) is substantial in drug development. Recently, deep learning has made good progress in the prediction of DTAs. Although relatively effective, due to the black-box nature of deep learning, these models are less biologically interpretable. In this study, we proposed a deep learning-based model, named AttentionDTA, with attention mechanism. The novelty of our work is to use attention mechanism to focus on key subsequences which are important in drug and protein sequences when predicting its affinity. We use two separate one-dimensional Convolution Neural Networks to extract the semantic information of drug's SMILES string and protein's amino acid sequence. Furthermore, four different attention mechanisms are developed and embedded to our model to explore the relationship between drug features and protein features. We conduct extensive experiments to demonstrate that AttentionDTA can effectively extract protein features related to drug information and drug features related to protein information to better predict drug target affinities. By visualizing the attention weight in the model, we found that even if the information of the binding site was never input during the inference process, AttentionDTA can still effectively enhance the role of the protein feature at the target site.

In bioinformatics, machine learning-based prediction of drug-target interaction (DTI) plays an important role in virtual screening of drug discovery. DTI prediction, which have been treated as a binary classification problem, depends on the concentration of two molecules, the interaction between two molecules, and other factors. The degree of affinity between a drug molecule (such as a drug compound) and a target molecule (such as a receptor or protein kinase) reflects how tightly the drug binds to a particular target and is quantified by the measurement which can reflect more detailed and specific information than binary relationship. In this study, we proposed an end-to-end model, named AttentionDTA, based on deep learning, which associates attention mechanism to predict the binding affinity of DTI. The novelty in this work is to use attentional mechanisms to consider which subsequences in a protein are more important for a drug and which subsequences in a drug are more important for a protein when predicting its affinity. So that the representational ability of the model is stronger. The model uses one-dimensional Convolution Neural Networks (1D-CNNs) to extract the abstract information of drug and protein, and makes the drug and protein representations mutually adapt through the attention mechanisms. We evaluate our model on two established drug-target affinity benchmark datasets, Davis and KIBA. The model outperforms DeepDTA, a state-of-the-art deep learning method for drug–target binding affinity prediction, with better Mean Squared Error (MSE), Concordance Index (CI), $r_{m}^{2}$ , and Area Under Precision Recall Curve (AUPR). Our results show that the attention-based model can effectively extract effective representations by calculating the weight of the representation between the drug and the protein. Finally, we visualize the attention weight. It proves our model can obtain the information of binding sites.