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Motivation Accurate inference of potential drug–protein interactions (DPIs) aids in understanding drug mechanisms and developing novel treatments. Existing deep learning models, however, struggle with accurate node representation in DPI prediction, limiting their performance. Results We propose a new computational framework that integrates global and local features of nodes in the drug–protein bipartite graph for efficient DPI inference. Initially, we employ pre-trained models to acquire fundamental knowledge of drugs and proteins and to determine their initial features. Subsequently, the MinHash and HyperLogLog algorithms are utilized to estimate the similarity and set cardinality between drug and protein subgraphs, serving as their local features. Then, an energy-constrained diffusion mechanism is integrated into the transformer architecture, capturing interdependencies between nodes in the drug–protein bipartite graph and extracting their global features. Finally, we fuse the local and global features of nodes and employ multilayer perceptrons to predict the likelihood of potential DPIs. A comprehensive and precise node representation guarantees efficient prediction of unknown DPIs by the model. Various experiments validate the accuracy and reliability of our model, with molecular docking results revealing its capability to identify potential DPIs not present in existing databases. This approach is expected to offer valuable insights for furthering drug repurposing and personalized medicine research. Availability and implementation Our code and data are accessible at: https://github.com/ZZCrazy00/DPI. [ABSTRACT FROM AUTHOR]

Summary Identifying the protein–peptide binding residues is fundamentally important to understand the mechanisms of protein functions and explore drug discovery. Although several computational methods have been developed, most of them highly rely on third-party tools or complex data preprocessing for feature design, easily resulting in low computational efficacy and suffering from low predictive performance. To address the limitations, we propose PepBCL, a novel BERT (Bidirectional Encoder Representation from Transformers) -based contrastive learning framework to predict the protein–peptide binding residues based on protein sequences only. PepBCL is an end-to-end predictive model that is independent of feature engineering. Specifically, we introduce a well pre-trained protein language model that can automatically extract and learn high-latent representations of protein sequences relevant for protein structures and functions. Further, we design a novel contrastive learning module to optimize the feature representations of binding residues underlying the imbalanced dataset. We demonstrate that our proposed method significantly outperforms the state-of-the-art methods under benchmarking comparison, and achieves more robust performance. Moreover, we found that we further improve the performance via the integration of traditional features and our learnt features. Interestingly, the interpretable analysis of our model highlights the flexibility and adaptability of deep learning-based protein language model to capture both conserved and non-conserved sequential characteristics of peptide-binding residues. Finally, to facilitate the use of our method, we establish an online predictive platform as the implementation of the proposed PepBCL, which is now available at http://server.wei-group.net/PepBCL/. Availability and implementation https://github.com/Ruheng-W/PepBCL. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation N4-acetylcytidine (ac4C) is the only acetylation modification that has been characterized in eukaryotic RNA, and is correlated with various human diseases. Laboratory identification of ac4C is complicated by factors, such as sample hydrolysis and high cost. Unfortunately, existing computational methods to identify ac4C do not achieve satisfactory performance. Results We developed a novel tool, DeepAc4C, which identifies ac4C using convolutional neural networks (CNNs) using hybrid features composed of physicochemical patterns and a distributed representation of nucleic acids. Our results show that the proposed model achieved better and more balanced performance than existing predictors. Furthermore, we evaluated the effect that specific features had on the model predictions and their interaction effects. Several interesting sequence motifs specific to ac4C were identified. Availability and implementation The webserver is freely accessible at https://ac4c.webmalab.cn/ , the source code and datasets are accessible at Zenodo with URL https://doi.org/10.5281/zenodo.5138047 and Github with URL https://github.com/wangchao-malab/DeepAc4C. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]