Both objective optimization and constraint satisfaction are crucial for solving constrained multiobjective optimization problems, but the existing evolutionary algorithms encounter difficulties in striking a good balance between them when tackling complex feasible regions. To address this issue, this article proposes a two-stage evolutionary algorithm, which adjusts the fitness evaluation strategies during the evolutionary process to adaptively balance objective optimization and constraint satisfaction. The proposed algorithm can switch between the two stages according to the status of the current population, enabling the population to cross the infeasible region and reach the feasible regions in one stage, and to spread along the feasible boundaries in the other stage. Experimental studies on four benchmark suites and three real-world applications demonstrate the superiority of the proposed algorithm over the state-of-the-art algorithms, especially on problems with complex feasible regions.

In silico reuse of old drugs (also known as drug repositioning) to treat common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked drugs, with potentially lower overall development costs and shorter development timelines. Therefore, there is a pressing need for computational drug repurposing methodologies to facilitate drug discovery. In this study, we propose a new method, called DRHGCN (Drug Repositioning based on the Heterogeneous information fusion Graph Convolutional Network), to discover potential drugs for a certain disease. To make full use of different topology information in different domains (i.e. drug–drug similarity, disease–disease similarity and drug–disease association networks), we first design inter- and intra-domain feature extraction modules by applying graph convolution operations to the networks to learn the embedding of drugs and diseases, instead of simply integrating the three networks into a heterogeneous network. Afterwards, we parallelly fuse the inter- and intra-domain embeddings to obtain the more representative embeddings of drug and disease. Lastly, we introduce a layer attention mechanism to combine embeddings from multiple graph convolution layers for further improving the prediction performance. We find that DRHGCN achieves high performance (the average AUROC is 0.934 and the average AUPR is 0.539) in four benchmark datasets, outperforming the current approaches. Importantly, we conducted molecular docking experiments on DRHGCN-predicted candidate drugs, providing several novel approved drugs for Alzheimer’s disease (e.g. benzatropine) and Parkinson’s disease (e.g. trihexyphenidyl and haloperidol).

In recent years, synthesizing drugs powered by artificial intelligence has brought great convenience to society. Since retrosynthetic analysis occupies an essential position in synthetic chemistry, it has received broad attention from researchers. In this review, we comprehensively summarize the development process of retrosynthesis in the context of deep learning. This review covers all aspects of retrosynthesis, including datasets, models and tools. Specifically, we report representative models from academia, in addition to a detailed description of the available and stable platforms in the industry. We also discuss the disadvantages of the existing models and provide potential future trends, so that more abecedarians will quickly understand and participate in the family of retrosynthesis planning.

The traditional covert communication channel relying on a third-party node is vulnerable to attack. The data are easily tampered with and the identity information of the communication party is fragile. Blockchain has the characteristics of decentralization and tamper resistance, which can effectively solve the above problems. In addition, some confidential information needs to be transmitted covertly in the transparent blockchain. A smart contract deployed in the blockchain to automatically realize its function can replace a centralized node to provide credible guarantee for communication. The diversity of parameters, data redundancy, and code programmability of smart contract make it an excellent carrier for covert communication under blockchain. In this article, we propose a covert communication model combined with smart contracts to covertly transfer information in the blockchain environment. To implement this model, we use the parameters in the contract to map the secret information sequence, and call the contract to transfer message. Voting contract and secret bidding contract are combined to instantiate the proposed model, and optimized versions of the two contracts are also proposed to reduce costs. Moreover, we use encryption algorithms and two-round protocols to ensure data privacy and design corresponding information embedding and transmission methods for different scenarios. To improve the concealment of communication, redundant options, effective price ranges, and invalid bids are set in two contracts, respectively. The experimental results show that the proposed model has tamper resistance and low complexity, and it is feasible to use this model for covert communication.

The advances in single-cell ribonucleic acid sequencing (scRNA-seq) allow researchers to explore cellular heterogeneity and human diseases at cell resolution. Cell clustering is a prerequisite in scRNA-seq analysis since it can recognize cell identities. However, the high dimensionality, noises and significant sparsity of scRNA-seq data have made it a big challenge. Although many methods have emerged, they still fail to fully explore the intrinsic properties of cells and the relationship among cells, which seriously affects the downstream clustering performance. Here, we propose a new deep contrastive clustering algorithm called scDCCA. It integrates a denoising auto-encoder and a dual contrastive learning module into a deep clustering framework to extract valuable features and realize cell clustering. Specifically, to better characterize and learn data representations robustly, scDCCA utilizes a denoising Zero-Inflated Negative Binomial model-based auto-encoder to extract low-dimensional features. Meanwhile, scDCCA incorporates a dual contrastive learning module to capture the pairwise proximity of cells. By increasing the similarities between positive pairs and the differences between negative ones, the contrasts at both the instance and the cluster level help the model learn more discriminative features and achieve better cell segregation. Furthermore, scDCCA joins feature learning with clustering, which realizes representation learning and cell clustering in an end-to-end manner. Experimental results of 14 real datasets validate that scDCCA outperforms eight state-of-the-art methods in terms of accuracy, generalizability, scalability and efficiency. Cell visualization and biological analysis demonstrate that scDCCA significantly improves clustering and facilitates downstream analysis for scRNA-seq data. The code is available at https://github.com/WJ319/scDCCA.