Background: Affinity prediction between molecule and protein is an important step of virtual screening, which is usually called drug-target affinity (DTA) prediction. Its accuracy directly influences the progress of drug development. Sequence-based drug-target affinity prediction can predict the affinity according to protein sequence, which is fast and can be applied to large datasets. However, due to the lack of protein structure information, the accuracy needs to be improved. Results: The proposed model which is called WGNN-DTA can be competent in drug-target affinity (DTA) and compound-protein interaction (CPI) prediction tasks. Various experiments are designed to verify the performance of the proposed method in different scenarios, which proves that WGNN-DTA has the advantages of simplicity and high accuracy. Moreover, because it does not need complex steps such as multiple sequence alignment (MSA), it has fast execution speed, and can be suitable for the screening of large databases. Conclusion: We construct protein and molecular graphs through sequence and SMILES that can effectively reflect their structures. To utilize the detail contact information of protein, graph neural network is used to extract features and predict the binding affinity based on the graphs, which is called weighted graph neural networks drug-target affinity predictor (WGNN-DTA). The proposed method has the advantages of simplicity and high accuracy.

Recent years have seen tremendous success in the design of novel drug molecules through deep generative models. Nevertheless, existing methods only generate drug-like molecules, which require additional structural optimization to be developed into actual drugs. In this study, a deep learning method for generating target-specific ligands was proposed. This method is useful when the dataset for target-specific ligands is limited. Deep learning methods can extract and learn features (representations) in a data-driven way with little or no human participation. Generative pretraining (GPT) was used to extract the contextual features of the molecule. Three different protein-encoding methods were used to extract the physicochemical properties and amino acid information of the target protein. Protein-encoding and molecular sequence information are combined to guide molecule generation. Transfer learning was used to fine-tune the pretrained model to generate molecules with better binding ability to the target protein. The model was validated using three different targets. The docking results show that our model is capable of generating new molecules with higher docking scores for the target proteins.

Prediction on drug–target interaction has always been a crucial link for drug discovery and repositioning, which have witnessed tremendous progress in recent years. Despite many efforts made, the existing representation learning or feature generation approaches of both drugs and proteins remain complicated as well as in high dimension. In addition, it is difficult for current methods to extract local important residues from sequence information while remaining focused on global structure. At the same time, massive data is not always easily accessible, which makes model learning from small datasets imminent. As a result, we propose an end-to-end learning model with SUPD and SUDD methods to encode drugs and proteins, which not only leave out the complicated feature extraction process but also greatly reduce the dimension of the embedding matrix. Meanwhile, we use a multi-view strategy with a transformer to extract local important residues of proteins for better representation learning. Finally, we evaluate our model on the BindingDB dataset in comparisons with different state-of-the-art models from comprehensive indicators. In results of 100% BindingDB, our AUC, AUPR, ACC, and F1-score reached 90.9%, 89.8%, 84.2%, and 84.3% respectively, which successively exceed the average values of other models by 2.2%, 2.3%, 2.6%, and 2.6%. Moreover, our model also generally surpasses their performance on 30% and 50% BindingDB datasets.

Single-cell transcriptomics is rapidly advancing our understanding of the composition of complex tissues and biological cells, and single-cell RNA sequencing (scRNA-seq) holds great potential for identifying and characterizing the cell composition of complex tissues. Cell type identification by analyzing scRNA-seq data is mostly limited by time-consuming and irreproducible manual annotation. As scRNA-seq technology scales to thousands of cells per experiment, the exponential increase in the number of cell samples makes manual annotation more difficult. On the other hand, the sparsity of gene transcriptome data remains a major challenge. This paper applied the idea of the transformer to single-cell classification tasks based on scRNA-seq data. We propose scTransSort, a cell-type annotation method pretrained with single-cell transcriptomics data. The scTransSort incorporates a method of representing genes as gene expression embedding blocks to reduce the sparsity of data used for cell type identification and reduce the computational complexity. The feature of scTransSort is that its implementation of intelligent information extraction for unordered data, automatically extracting valid features of cell types without the need for manually labeled features and additional references. In experiments on cells from 35 human and 26 mouse tissues, scTransSort successfully elucidated its high accuracy and high performance for cell type identification, and demonstrated its own high robustness and generalization ability.

Recent advances in single-cell RNA sequencing (scRNA-seq) have accelerated the development of techniques to classify thousands of cells through transcriptome profiling. As more and more scRNA-seq data become available, supervised cell type classification methods using externally well-annotated source data become more popular than unsupervised clustering algorithms. However, accurate cellular annotation of single cell transcription data remains a significant challenge. Here, we propose a hybrid network structure called TransCluster, which uses linear discriminant analysis and a modified Transformer to enhance feature learning. It is a cell-type identification tool for single-cell transcriptomic maps. It shows high accuracy and robustness in many cell data sets of different human tissues. It is superior to other known methods in external test data set. To our knowledge, TransCluster is the first attempt to use Transformer for annotating cell types of scRNA-seq, which greatly improves the accuracy of cell-type identification.