EDC-DTI: An end-to-end deep collaborative learning model based on multiple information for drug-target interactions prediction

BackgroundIdentification of drug target interactions (DTI) is an important part of the drug discovery process. Since prediction of DTI using laboratory tests is time consuming and laborious, automated tools using computational intelligence (CI) techniques become essential. The prediction of DTI is a challenging process due to the absence of known drug-target relationship and no experimentally verified negative samples. The datasets with limited or unbalanced data, do not perform well. The models that use heterogeneous networks, non-linear fusion techniques, and heuristic similarity selection may need a lot of computational power and experience to implement and fine-tune. The latest developments in machine learning (ML) and deep learning (DL) models can be employed for effective DTI prediction process.ResultsTo that end, this study develops a novel DTI Prediction model, namely, DTIP-WINDGRU Drug-Target Interaction Prediction with Wind-Enhanced GRU. The major aim is to determine the DTIs in both labelled and unlabelled samples accurately compared to traditional wet lab experiments. To accomplish this, the proposed DTIP-WINDGRU model primarily performs pre-processing and class labelling. In addition, drug-to-drug (D-D) and target-to-target (T-T) interactions are employed to initialize the weights of the GRU model and are employed for the, DTI prediction process. Finally, the Wind Driven Optimization (WDO) algorithm is utilized to optimally choose the hyperparameters involved in the GRU model.ConclusionsFor ensuring the effectual prediction results of the DTIP-WINDGRU model, a widespread experimentation process was carried out using four datasets. This comprehensive comparative study highlighted the better performance of the DTIP-WINDGRU model over existing techniques.

Identifying drug–target interactions (DTIs) is important for drug discovery. However, searching all drug–target spaces poses a major bottleneck. Therefore, recently many deep learning models have been proposed to address this problem. However, the developers of these deep learning models have neglected interpretability in model construction, which is closely related to a model’s performance. We hypothesized that training a model to predict important regions on a protein sequence would increase DTI prediction performance and provide a more interpretable model. Consequently, we constructed a deep learning model, named Highlights on Target Sequences (HoTS), which predicts binding regions (BRs) between a protein sequence and a drug ligand, as well as DTIs between them. To train the model, we collected complexes of protein–ligand interactions and protein sequences of binding sites and pretrained the model to predict BRs for a given protein sequence–ligand pair via object detection employing transformers. After pretraining the BR prediction, we trained the model to predict DTIs from a compound token designed to assign attention to BRs. We confirmed that training the BRs prediction model indeed improved the DTI prediction performance. The proposed HoTS model showed good performance in BR prediction on independent test datasets even though it does not use 3D structure information in its prediction. Furthermore, the HoTS model achieved the best performance in DTI prediction on test datasets. Additional analysis confirmed the appropriate attention for BRs and the importance of transformers in BR and DTI prediction. The source code is available on GitHub (https://github.com/GIST-CSBL/HoTS).

Drug-target Interactions (DTIs) prediction plays a central role in drug discovery. Computational methods in DTIs prediction have gained more attention because carrying out in vitro and in vivo experiments on a large scale is costly and time-consuming. Machine learning methods, especially deep learning, are widely applied to DTIs prediction. In this study, the main goal is to provide a comprehensive overview of deep learning-based DTIs prediction approaches. Here, we investigate the existing approaches from multiple perspectives. We explore these approaches to find out which deep network architectures are utilized to extract features from drug compound and protein sequences. Also, the advantages and limitations of each architecture are analyzed and compared. Moreover, we explore the process of how to combine descriptors for drug and protein features. Likewise, a list of datasets that are commonly used in DTIs prediction is investigated. Finally, current challenges are discussed and a short future outlook of deep learning in DTI prediction is given.

EA-based hyperparameter optimization of hybrid deep learning models for effective drug-target interactions prediction

BackgroundIn silico drug-target interaction (DTI) prediction plays an integral role in drug repositioning: the discovery of new uses for existing drugs. One popular method of drug repositioning is network-based DTI prediction, which uses complex network theory to predict DTIs from a drug-target network. Currently, most network-based DTI prediction is based on machine learning – methods such as Restricted Boltzmann Machines (RBM) or Support Vector Machines (SVM). These methods require additional information about the characteristics of drugs, targets and DTIs, such as chemical structure, genome sequence, binding types, causes of interactions, etc., and do not perform satisfactorily when such information is unavailable. We propose a new, alternative method for DTI prediction that makes use of only network topology information attempting to solve this problem.ResultsWe compare our method for DTI prediction against the well-known RBM approach. We show that when applied to the MATADOR database, our approach based on node neighborhoods yield higher precision for high-ranking predictions than RBM when no information regarding DTI types is available.ConclusionThis demonstrates that approaches purely based on network topology provide a more suitable approach to DTI prediction in the many real-life situations where little or no prior knowledge is available about the characteristics of drugs, targets, or their interactions.

Identification of Drug-Target Interactions (DTIs) is an essential step in drug discovery and repositioning. DTI prediction based on biological experiments is time-consuming and expensive. In recent years, graph learning-based methods have aroused widespread interest and shown certain advantages on this task, where the DTI prediction is often modeled as a binary classification problem of the nodes composed of drug and protein pairs (DPPs). Nevertheless, in many real applications, labeled data are very limited and expensive to obtain. With only a few thousand labeled data, models could hardly recognize comprehensive patterns of DPP node representations, and are unable to capture enough commonsense knowledge, which is required in DTI prediction. Supervised contrastive learning gives an aligned representation of DPP node representations with the same class label. In embedding space, DPP node representations with the same label are pulled together, and those with different labels are pushed apart. We propose an end-to-end supervised graph co-contrastive learning model for DTI prediction directly from heterogeneous networks. By contrasting the topology structures and semantic features of the drug-protein-pair network, as well as the new selection strategy of positive and negative samples, SGCL-DTI generates a contrastive loss to guide the model optimization in a supervised manner. Comprehensive experiments on three public datasets demonstrate that our model outperforms the SOTA methods significantly on the task of DTI prediction, especially in the case of cold start. Furthermore, SGCL-DTI provides a new research perspective of contrastive learning for DTI prediction. The research shows that this method has certain applicability in the discovery of drugs, the identification of drug-target pairs and so on.

Drug discovery is a long, resource-intensive process with high failure rates. Traditional experimental identification of drug-target interactions (DTIs) is especially time-consuming and costly. This comprehensive review examines how Artificial Intelligence (AI) and Machine Learning (ML) are transforming DTI prediction, offering substantial potential to reduce drug development time and costs. The review provides a detailed examination of AI/ML-based techniques, detailing data representations for drugs, targets, and their interactions through joint drug-target processing. The review extensively discusses feature extraction and engineering methods, including the construction of interaction-specific features. It also encompasses a broad range of learning paradigms and model architectures, including supervised learning, advanced Graph Neural Networks (GNNs), Deep Learning (DL) models, and hybrid approaches. We further examine training protocols and robust evaluation metrics crucial for assessing model generalization. Ultimately, this review highlights the capacity of these advanced AI/ML methods to deliver more accurate, scalable, and interpretable solutions for DTI prediction. This is crucial for accelerating key stages of drug development, including lead compound identification, off-target profiling, drug repurposing, polypharmacology analysis, and the realization of precision medicine.

<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Motivation:</i> The prediction of drug-target interaction (DTI) from heterogeneous biological data is critical to predict drugs and therapeutic targets for known diseases such as tumor and bowel disease. The study of DTI based on drug representation learning can strengthen or integrate our knowledge of pharmacological and chemical phenomena. Therefore, there is a strong motivation to develop effective methods that can detect these potential drug-target interactions. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Results:</i> We have developed a novel Knowledge-Enhanced Multi-View framework (KEMV) to predict unknown DTIs from pharmacological data and chemical data on a large scale. The proposed method consists of two steps: (i) learning more comprehensive drug representations via the proposed multi-view attention mechanism, which bridges pharmacological and chemical information, and interactively summarizes the attention values depending on varying interactions between different pairs of drug features. (ii) predicting unknown drug-target interactions based on the drug and target representations. The method is tested on real-world dataset KEGG with three classes of important drug–target interactions involving enzymes, ion channels, and G-protein-coupled receptors. Our framework is proven to uncover potential DTIs with scientific evidences explaining the mechanism of the interactions through the processing of high-dimensional, heterogeneous, and sparse drug data. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Availability:</i> The originality of the proposed method lies in the attentive integration of pharmacological and chemical information for representation of drug candidate compounds and the prediction of drug-target interaction toward drug discovery in a unified framework. Our results are reproducible and and code is available at: <uri xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">https://github.com/YuanKQ/DTI-Prediction</uri> .

MotivationAccurately predicting drug–target interaction (DTI) is a crucial step to drug discovery. Recently, deep learning techniques have been widely used for DTI prediction and achieved significant performance improvement. One challenge in building deep learning models for DTI prediction is how to appropriately represent drugs and targets. Target distance map and molecular graph are low dimensional and informative representations, which however have not been jointly used in DTI prediction. Another challenge is how to effectively model the mutual impact between drugs and targets. Though attention mechanism has been used to capture the one-way impact of targets on drugs or vice versa, the mutual impact between drugs and targets has not yet been explored, which is very important in predicting their interactions.ResultsTherefore, in this article we propose MINN-DTI, a new model for DTI prediction. MINN-DTI combines an interacting-transformer module (called Interformer) with an improved Communicative Message Passing Neural Network (CMPNN) (called Inter-CMPNN) to better capture the two-way impact between drugs and targets, which are represented by molecular graph and distance map, respectively. The proposed method obtains better performance than the state-of-the-art methods on three benchmark datasets: DUD-E, human and BindingDB. MINN-DTI also provides good interpretability by assigning larger weights to the amino acids and atoms that contribute more to the interactions between drugs and targets.Availability and implementationThe data and code of this study are available at https://github.com/admislf/MINN-DTI.

BackgroundIdentifying drug-target interaction is a key element in drug discovery. In silico prediction of drug-target interaction can speed up the process of identifying unknown interactions between drugs and target proteins. In recent studies, handcrafted features, similarity metrics and machine learning methods have been proposed for predicting drug-target interactions. However, these methods cannot fully learn the underlying relations between drugs and targets. In this paper, we propose anew framework for drug-target interaction prediction that learns latent features from drug-target interaction network.ResultsWe present a framework to utilize the network topology and identify interacting and non-interacting drug-target pairs. We model the problem as a semi-bipartite graph in which we are able to use drug-drug and protein-protein similarity in a drug-protein network. We have then used a graph labeling method for vertex ordering in our graph embedding process. Finally, we employed deep neural network to learn the complex pattern of interacting pairs from embedded graphs. We show our approach is able to learn sophisticated drug-target topological features and outperforms other state-of-the-art approaches.ConclusionsThe proposed learning model on semi-bipartite graph model, can integrate drug-drug and protein-protein similarities which are semantically different than drug-protein information in a drug-target interaction network. We show our model can determine interaction likelihood for each drug-target pair and outperform other heuristics.

Electricity load forecasting is a crucial undertaking within all the deregulated markets globally. Among the research challenges on a global scale, the investigation of deep transfer learning (DTL) in the field of electricity load forecasting represents a fundamental effort that can inform artificial intelligence applications in general. In this paper, a comprehensive study is reported regarding day-ahead electricity load forecasting. For this purpose, three sequence-to-sequence (Seq2seq) deep learning (DL) models are used, namely the multilayer perceptron (MLP), the convolutional neural network (CNN) and the ensemble learning model (ELM), which consists of the weighted combination of the outputs of MLP and CNN models. Also, the study focuses on the development of different forecasting strategies based on DTL, emphasizing the way the datasets are trained and fine-tuned for higher forecasting accuracy. In order to implement the forecasting strategies using deep learning models, load datasets from three Greek islands, Rhodes, Lesvos, and Chios, are used. The main purpose is to apply DTL for day-ahead predictions (1–24 h) for each month of the year for the Chios dataset after training and fine-tuning the models using the datasets of the three islands in various combinations. Four DTL strategies are illustrated. In the first strategy (DTL Case 1), each of the three DL models is trained using only the Lesvos dataset, while fine-tuning is performed on the dataset of Chios island, in order to create day-ahead predictions for the Chios load. In the second strategy (DTL Case 2), data from both Lesvos and Rhodes concurrently are used for the DL model training period, and fine-tuning is performed on the data from Chios. The third DTL strategy (DTL Case 3) involves the training of the DL models using the Lesvos dataset, and the testing period is performed directly on the Chios dataset without fine-tuning. The fourth strategy is a multi-task deep learning (MTDL) approach, which has been extensively studied in recent years. In MTDL, the three DL models are trained simultaneously on all three datasets and the final predictions are made on the unknown part of the dataset of Chios. The results obtained demonstrate that DTL can be applied with high efficiency for day-ahead load forecasting. Specifically, DTL Case 1 and 2 outperformed MTDL in terms of load prediction accuracy. Regarding the DL models, all three exhibit very high prediction accuracy, especially in the two cases with fine-tuning. The ELM excels compared to the single models. More specifically, for conducting day-ahead predictions, it is concluded that the MLP model presents the best monthly forecasts with MAPE values of 6.24% and 6.01% for the first two cases, the CNN model presents the best monthly forecasts with MAPE values of 5.57% and 5.60%, respectively, and the ELM model achieves the best monthly forecasts with MAPE values of 5.29% and 5.31%, respectively, indicating the very high accuracy it can achieve.

Drug-target interaction prediction based on metapaths and simplified neighbor aggregation.

BackgroundDrug-target interaction (DTI) prediction plays a pivotal role in drug discovery and drug repositioning, enabling the identification of potential drug candidates. However, most previous approaches often do not fully utilize the complementary relationships among multiple biological networks, which limits their ability to learn more consistent representations. Additionally, the selection strategy of negative samples significantly affects the performance of contrastive learning methods.ResultsIn this study, we propose CCL-ASPS, a novel deep learning model that incorporates Collaborative Contrastive Learning (CCL) and Adaptive Self-Paced Sampling strategy (ASPS) for drug-target interaction prediction. CCL-ASPS leverages multiple networks to learn the fused embeddings of drugs and targets, ensuring their consistent representations from individual networks. Furthermore, ASPS dynamically selects more informative negative sample pairs for contrastive learning. Experiment results on the established dataset demonstrate that CCL-ASPS achieves significant improvements compared to current state-of-the-art methods. Moreover, ablation experiments confirm the contributions of the proposed CCL and ASPS strategies.ConclusionsBy integrating Collaborative Contrastive Learning and Adaptive Self-Paced Sampling, the proposed CCL-ASPS effectively addresses the limitations of previous methods. This study demonstrates that CCL-ASPS achieves notable improvements in DTI predictive performance compared to current state-of-the-art approaches. The case study and cold start experiments further illustrate the capability of CCL-ASPS to effectively predict previously unknown DTI, potentially facilitating the identification of new drug-target interactions.

We aimed at comparing intratumoral and peritumoral deep learning, radiomics, and fusion models in predicting KRAS mutations in rectal cancer using endorectal ultrasound imaging. This study included 304 patients with rectal cancer from Fujian Medical University Union Hospital. The patients were randomly divided into a training group (213 patients) and a test group (91 patients) at a 7:3 ratio. Radiomics and deep learning models were established using primary tumor and peritumoral images. In the optimally performing regions-of-interest, two fusion strategies, a feature-based and a decision-based model, were employed to build the fusion models. The Shapley additive explanation (SHAP) method was used to evaluate the significance of features in the optimal radiomics, deep learning, and fusion models. The performance of each model was assessed using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). In the test cohort, both the radiomics and deep learning models exhibited optimal performance with a 10-pixel patch extension, yielding AUC values of 0.824 and 0.856, respectively. The feature-based DLRexpand10_FB model attained the highest AUC (0.896) across all study sets. In addition, the DLRexpand10_FB model demonstrated excellent sensitivity, specificity, and DCA. SHAP analysis underscored the deep learning feature (DL_1) as the most significant factor in the hybrid model. The feature-based fusion model DLRexpand10_FB can be employed to predict KRAS gene mutations based on pretreatment endorectal ultrasound images of rectal cancer. The integration of peritumoral regions enhanced the predictive performance of both the radiomics and deep learning models.

PurposeTo conduct a head-to-head comparison between deep learning (DL) and radiomics models across institutions for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) and to investigate the model robustness and generalizability through rigorous internal and external validation.MethodsThis retrospective study included 2304 preoperative images of 576 HCC lesions from two centers, with MVI status determined by postoperative histopathology. We developed DL and radiomics models for predicting the presence of MVI using B-mode ultrasound, contrast-enhanced ultrasound (CEUS) at the arterial, portal, and delayed phases, and a combined modality (B + CEUS). For radiomics, we constructed models with enlarged vs. original regions of interest (ROIs). A cross-validation approach was performed by training models on one center’s dataset and validating the other, and vice versa. This allowed assessment of the validity of different ultrasound modalities and the cross-center robustness of the models. The optimal model combined with alpha-fetoprotein (AFP) was also validated. The head-to-head comparison was based on the area under the receiver operating characteristic curve (AUC).ResultsThirteen DL models and 25 radiomics models using different ultrasound modalities were constructed and compared. B + CEUS was the optimal modality for both DL and radiomics models. The DL model achieved AUCs of 0.802–0.818 internally and 0.667–0.688 externally across the two centers, whereas radiomics achieved AUCs of 0.749–0.869 internally and 0.646–0.697 externally. The radiomics models showed overall improvement with enlarged ROIs (P < 0.05 for both CEUS and B + CEUS modalities). The DL models showed good cross-institutional robustness (P > 0.05 for all modalities, 1.6–2.1% differences in AUC for the optimal modality), whereas the radiomics models had relatively limited robustness across the two centers (12% drop-off in AUC for the optimal modality). Adding AFP improved the DL models (P < 0.05 externally) and well maintained the robustness, but did not benefit the radiomics model (P > 0.05).ConclusionCross-institutional validation indicated that DL demonstrated better robustness than radiomics for preoperative MVI prediction in patients with HCC, representing a promising solution to non-standardized ultrasound examination procedures.