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Background: Obtaining accurate drug–target binding affinity (DTA) information is significant for drug discovery and drug repositioning. Although some methods have been proposed for predicting DTA, the features of proteins and drugs still need to be further analyzed. Recently, deep learning has been successfully used in many fields. Hence, designing a more effective deep learning method for predicting DTA remains attractive. Results: Dynamic graph DTA (DGDTA), which uses a dynamic graph attention network combined with a bidirectional long short-term memory (Bi-LSTM) network to predict DTA is proposed in this paper. DGDTA adopts drug compound as input according to its corresponding simplified molecular input line entry system (SMILES) and protein amino acid sequence. First, each drug is considered a graph of interactions between atoms and edges, and dynamic attention scores are used to consider which atoms and edges in the drug are most important for predicting DTA. Then, Bi-LSTM is used to better extract the contextual information features of protein amino acid sequences. Finally, after combining the obtained drug and protein feature vectors, the DTA is predicted by a fully connected layer. The source code is available from GitHub at https://github.com/luojunwei/DGDTA. Conclusions: The experimental results show that DGDTA can predict DTA more accurately than some other methods. [ABSTRACT FROM AUTHOR]

Background: Drug-target binding affinity (DTA) prediction is important for the rapid development of drug discovery. Compared to traditional methods, deep learning methods provide a new way for DTA prediction to achieve good performance without much knowledge of the biochemical background. However, there are still room for improvement in DTA prediction: (1) only focusing on the information of the atom leads to an incomplete representation of the molecular graph; (2) the self-supervised learning method could be introduced for protein representation. Results: In this paper, a DTA prediction model using the deep learning method is proposed, which uses an undirected-CMPNN for molecular embedding and combines CPCProt and MLM models for protein embedding. An attention mechanism is introduced to discover the important part of the protein sequence. The proposed method is evaluated on the datasets Ki and Davis, and the model outperformed other deep learning methods. Conclusions: The proposed model improves the performance of the DTA prediction, which provides a novel strategy for deep learning-based virtual screening methods. [ABSTRACT FROM AUTHOR]

Background: The Drug–Target Interaction (DTI) prediction uses a drug molecule and a protein sequence as inputs to predict the binding affinity value. In recent years, deep learning-based models have gotten more attention. These methods have two modules: the feature extraction module and the task prediction module. In most deep learning-based approaches, a simple task prediction loss (i.e., categorical cross entropy for the classification task and mean squared error for the regression task) is used to learn the model. In machine learning, contrastive-based loss functions are developed to learn more discriminative feature space. In a deep learning-based model, extracting more discriminative feature space leads to performance improvement for the task prediction module. Results: In this paper, we have used multimodal knowledge as input and proposed an attention-based fusion technique to combine this knowledge. Also, we investigate how utilizing contrastive loss function along the task prediction loss could help the approach to learn a more powerful model. Four contrastive loss functions are considered: (1) max-margin contrastive loss function, (2) triplet loss function, (3) Multi-class N-pair Loss Objective, and (4) NT-Xent loss function. The proposed model is evaluated using four well-known datasets: Wang et al. dataset, Luo's dataset, Davis, and KIBA datasets. Conclusions: Accordingly, after reviewing the state-of-the-art methods, we developed a multimodal feature extraction network by combining protein sequences and drug molecules, along with protein–protein interaction networks and drug–drug interaction networks. The results show it performs significantly better than the comparable state-of-the-art approaches. [ABSTRACT FROM AUTHOR]

Background: Drug–target interaction (DTI) prediction plays a crucial role in drug discovery. Although the advanced deep learning has shown promising results in predicting DTIs, it still needs improvements in two aspects: (1) encoding method, in which the existing encoding method, character encoding, overlooks chemical textual information of atoms with multiple characters and chemical functional groups; as well as (2) the architecture of deep model, which should focus on multiple chemical patterns in drug and target representations. Results: In this paper, we propose a multi-granularity multi-scaled self-attention (SAN) model by alleviating the above problems. Specifically, in process of encoding, we investigate a segmentation method for drug and protein sequences and then label the segmented groups as the multi-granularity representations. Moreover, in order to enhance the various local patterns in these multi-granularity representations, a multi-scaled SAN is built and exploited to generate deep representations of drugs and targets. Finally, our proposed model predicts DTIs based on the fusion of these deep representations. Our proposed model is evaluated on two benchmark datasets, KIBA and Davis. The experimental results reveal that our proposed model yields better prediction accuracy than strong baseline models. Conclusion: Our proposed multi-granularity encoding method and multi-scaled SAN model improve DTI prediction by encoding the chemical textual information of drugs and targets and extracting their various local patterns, respectively. [ABSTRACT FROM AUTHOR]

Virulencefactors (VFs) are key molecules that enable pathogens to evade the immune systems of the host. These factors are crucial for revealing the pathogenic processes of microbes and drug discovery. Identification of virulence factors in microbes become an important problem in the field of bioinformatics. To address this problem, this study proposes a novel model DTVF (Deep Transfer Learning for Virulence Factor Prediction), which integrates the ProtT5 protein sequence extraction model with a dual-channel deep learning model. In the dual-channel deep learning model, we innovatively integrate long short-term memory (LSTM) with convolutional neural networks (CNNs), creating a novel integrated architecture. Furthermore, by incorporating the attention mechanism, the accuracy of VF detection was significantly enhanced. We evaluated the DTVF model against other excellent-performing models in the field. DTVF demonstrates superior performance, achieving an accuracy rate of 84.55% and an AUROC of 92.08% on the benchmark dataset. DTVF shows state-of-the-art performance in this field, surpassing the existing models in nearly all metrics. To facilitate the use of biologists, we have also developed an interactive web-based user interface version of DTVF based on Gradio. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading diseases threatening human life and health worldwide. Peptide-based therapies have attracted much attention in recent years. Therefore, the precise prediction of anticancer peptides (ACPs) is crucial for discovering and designing novel cancer treatments. In this study, we proposed a novel machine learning framework (GRDF) that incorporates deep graphical representation and deep forest architecture for identifying ACPs. Specifically, GRDF extracts graphical features based on the physicochemical properties of peptides and integrates their evolutionary information along with binary profiles for constructing models. Moreover, we employ the deep forest algorithm, which adopts a layer-by-layer cascade architecture similar to deep neural networks, enabling excellent performance on small datasets but without complicated tuning of hyperparameters. The experiment shows GRDF exhibits state-of-the-art performance on two elaborate datasets (Set 1 and Set 2), achieving 77.12% accuracy and 77.54% F1-score on Set 1, as well as 94.10% accuracy and 94.15% F1-score on Set 2, exceeding existing ACP prediction methods. Our models exhibit greater robustness than the baseline algorithms commonly used for other sequence analysis tasks. In addition, GRDF is well-interpretable, enabling researchers to better understand the features of peptide sequences. The promising results demonstrate that GRDF is remarkably effective in identifying ACPs. Therefore, the framework presented in this study could assist researchers in facilitating the discovery of anticancer peptides and contribute to developing novel cancer treatments. [ABSTRACT FROM AUTHOR]

Background: Compound–protein interaction site and binding affinity predictions are crucial for drug discovery and drug design. In recent years, many deep learning-based methods have been proposed for predications related to compound–protein interaction. For protein inputs, how to make use of protein primary sequence and tertiary structure information has impact on prediction results. Results: In this study, we propose a deep learning model based on a multi-objective neural network, which involves a multi-objective neural network for compound–protein interaction site and binding affinity prediction. We used several kinds of self-supervised protein embeddings to enrich our protein inputs and used convolutional neural networks to extract features from them. Our results demonstrate that our model had improvements in terms of interaction site prediction and affinity prediction compared to previous models. In a case study, our model could better predict binding sites, which also showed its effectiveness. Conclusion: These results suggest that our model could be a helpful tool for compound–protein related predictions. [ABSTRACT FROM AUTHOR]

Drug–target protein interaction (DTI) identification is fundamental for drug discovery and drug repositioning, because therapeutic drugs act on disease-causing proteins. However, the DTI identification process often requires expensive and time-consuming tasks, including biological experiments involving large numbers of candidate compounds. Thus, a variety of computation approaches have been developed. Of the many approaches available, chemo-genomics feature-based methods have attracted considerable attention. These methods compute the feature descriptors of drugs and proteins as the input data to train machine and deep learning models to enable accurate prediction of unknown DTIs. In addition, attention-based learning methods have been proposed to identify and interpret DTI mechanisms. However, improvements are needed for enhancing prediction performance and DTI mechanism elucidation. To address these problems, we developed an attention-based method designated the interpretable cross-attention network (ICAN), which predicts DTIs using the Simplified Molecular Input Line Entry System of drugs and amino acid sequences of target proteins. We optimized the attention mechanism architecture by exploring the cross-attention or self-attention, attention layer depth, and selection of the context matrixes from the attention mechanism. We found that a plain attention mechanism that decodes drug-related protein context features without any protein-related drug context features effectively achieved high performance. The ICAN outperformed state-of-the-art methods in several metrics on the DAVIS dataset and first revealed with statistical significance that some weighted sites in the cross-attention weight matrix represent experimental binding sites, thus demonstrating the high interpretability of the results. The program is freely available at https://github.com/kuratahiroyuki/ICAN. [ABSTRACT FROM AUTHOR]