Carcinomas are complex ecosystems composed of cancer, stromal and immune cells. Communication between these cells and their microenvironments induces cancer progression and causes therapy resistance. In order to improve the treatment of cancers, it is essential to quantify crosstalk between and within various cell types in a tumour microenvironment. Focusing on the coordinated expression patterns of ligands and cognate receptors, cell–cell communication can be inferred through ligand–receptor interactions (LRIs). In this manuscript, we carry out the following work: (i) introduce pipeline for ligand–receptor-mediated intercellular communication estimation from single-cell transcriptomics and list a few available LRI-related databases and visualization tools; (ii) demonstrate seven classical intercellular communication scoring strategies, highlight four types of representative intercellular communication inference methods, including network-based approaches, machine learning-based approaches, spatial information-based approaches and other approaches; (iii) summarize the evaluation and validation avenues for intercellular communication inference and analyze the advantages and limitations for the above four types of cell–cell communication methods; (iv) comment several major challenges while provide further research directions for intercellular communication analysis in the tumour microenvironments. We anticipate that this work helps to better understand intercellular crosstalk and to further develop powerful cell–cell communication estimation tools for tumor-targeted therapy.

Background: Identifying possible drug-target interactions (DTIs) has become an important task in drug research and development. Although high-throughput screening is becoming available, experimental methods narrow down the validation space because of extremely high cost, low success rate, and time consumption. Therefore, various computational models have been exploited to infer DTI candidates. Methods: We introduced relevant databases and packages, mainly provided a comprehensive review of computational models for DTI identification, including network-based algorithms and machine learning-based methods. Specially, machine learning-based methods mainly include bipartite local model, matrix factorization, regularized least squares, and deep learning. Results: Although computational methods have obtained significant improvement in the process of DTI prediction, these models have their limitations. We discussed potential avenues for boosting DTI prediction accuracy as well as further directions.

As increasing experimental studies have shown that microRNAs (miRNAs) are closely related to multiple biological processes and the prevention, diagnosis and treatment of human diseases, a growing number of researchers are focusing on the identification of associations between miRNAs and diseases. Identifying such associations purely via experiments is costly and demanding, which prompts researchers to develop computational methods to complement the experiments. In this paper, a novel prediction model named Ensemble of Kernel Ridge Regression based MiRNA-Disease Association prediction (EKRRMDA) was developed. EKRRMDA obtained features of miRNAs and diseases by integrating the disease semantic similarity, the miRNA functional similarity and the Gaussian interaction profile kernel similarity for diseases and miRNAs. Under the computational framework that utilized ensemble learning and feature dimensionality reduction, multiple base classifiers that combined two Kernel Ridge Regression classifiers from the miRNA side and disease side, respectively, were obtained based on random selection of features. Then average strategy for these base classifiers was adopted to obtain final association scores of miRNA-disease pairs. In the global and local leave-one-out cross validation, EKRRMDA attained the AUCs of 0.9314 and 0.8618, respectively. Moreover, the model’s average AUC with standard deviation in 5-fold cross validation was 0.9275 ± 0.0008. In addition, we implemented three different types of case studies on predicting miRNAs associated with five important diseases. As a result, there were 90% (Esophageal Neoplasms), 86% (Kidney Neoplasms), 86% (Lymphoma), 98% (Lung Neoplasms), and 96% (Breast Neoplasms) of the top 50 predicted miRNAs verified to have associations with these diseases.

The outbreak of a novel febrile respiratory disease called COVID-19, caused by a newfound coronavirus SARS-CoV-2, has brought a worldwide attention. Prioritizing approved drugs is critical for quick clinical trials against COVID-19. In this study, we first manually curated three Virus-Drug Association (VDA) datasets. By incorporating VDAs with the similarity between drugs and that between viruses, we constructed a heterogeneous Virus-Drug network. A novel Random Walk with Restart method (VDA-RWR) was then developed to identify possible VDAs related to SARS-CoV-2. We compared VDA-RWR with three state-of-the-art association prediction models based on fivefold cross-validations (CVs) on viruses, drugs and virus-drug associations on three datasets. VDA-RWR obtained the best AUCs for the three fivefold CVs, significantly outperforming other methods. We found two small molecules coming together on the three datasets, that is, remdesivir and ribavirin. These two chemical agents have higher molecular binding energies of − 7.0 kcal/mol and − 6.59 kcal/mol with the domain bound structure of the human receptor angiotensin converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein, respectively. Interestingly, for the first time, experimental results suggested that navitoclax could be potentially applied to stop SARS-CoV-2 and remains to further validation.