Drug-target Interaction Prediction Research Articles

Graph-DTI: A New Model for Drug-target Interaction Prediction Based on Heterogenous Network Graph Embedding.

In this study, we aimed to develop a new end-to-end learning model called Graph-Drug-Target Interaction (DTI), which integrates various types of information in the heterogeneous network data, and to explore automatic learning of the topology-maintaining representations of drugs and targets, thereby effectively contributing to the prediction of DTI. Precise predictions of DTI can guide drug discovery and development. Most machine learning algorithms integrate multiple data sources and combine them with common embedding methods. However, the relationship between the drugs and target proteins is not well reported. Although some existing studies have used heterogeneous network graphs for DTI prediction, there are many limitations in the neighborhood information between the nodes in the heterogeneous network graphs. We studied the drug-drug interaction (DDI) and DTI from DrugBank Version 3.0, protein-protein interaction (PPI) from the human protein reference database Release 9, drug structure similarity from Morgan fingerprints of radius 2 and calculated by RDKit, and protein sequence similarity from Smith-Waterman score. Our study consists of three major components. First, various drugs and target proteins were integrated, and a heterogeneous network was established based on a series of data sets. Second, the graph neural networks-inspired graph auto-encoding method was used to extract high-order structural information from the heterogeneous networks, thereby revealing the description of nodes (drugs and proteins) and their topological neighbors. Finally, potential DTI prediction was made, and the obtained samples were sent to the classifier for secondary classification. The performance of Graph-DTI and all baseline methods was evaluated using the sums of the area under the precision-recall curve (AUPR) and the area under the receiver operating characteristic curve (AUC). The results indicated that Graph-DTI outperformed the baseline methods in both performance results. Compared with other baseline DTI prediction methods, the results showed that Graph-DTI had better prediction performance. Additionally, in this study, we effectively classified drugs corresponding to different targets and vice versa. The above findings showed that Graph-DTI provided a powerful tool for drug research, development, and repositioning. Graph- DTI can serve as a drug development and repositioning tool more effectively than previous studies that did not use heterogeneous network graph embedding.

NFSA-DTI: A Novel Drug-Target Interaction Prediction Model Using Neural Fingerprint and Self-Attention Mechanism.

Existing deep learning methods have shown outstanding performance in predicting drug-target interactions. However, they still have limitations: (1) the over-reliance on locally extracted features by some single encoders, with insufficient consideration of global features, and (2) the inadequate modeling and learning of local crucial interaction sites in drug-target interaction pairs. In this study, we propose a novel drug-target interaction prediction model called the Neural Fingerprint and Self-Attention Mechanism (NFSA-DTI), which effectively integrates the local information of drug molecules and target sequences with their respective global features. The neural fingerprint method is used in this model to extract global features of drug molecules, while the self-attention mechanism is utilized to enhance CNN's capability in capturing the long-distance dependencies between the subsequences in the target amino acid sequence. In the feature fusion module, we improve the bilinear attention network by incorporating attention pooling, which enhances the model's ability to learn local crucial interaction sites in the drug-target pair. The experimental results on three benchmark datasets demonstrated that NFSA-DTI outperformed all baseline models in predictive performance. Furthermore, case studies illustrated that our model could provide valuable insights for drug discovery. Moreover, our model offers molecular-level interpretations.

Drug-Target Prediction Based on Dynamic Heterogeneous Graph Convolutional Network.

Novel drug-target interaction (DTI) prediction is crucial in drug discovery and repositioning. Recently, graph neural network (GNN) has shown promising results in identifying DTI by using thresholds to construct heterogeneous graphs. However, an empirically selected threshold can lead to loss of valuable information, especially in sparse networks, a common scenario in DTI prediction. To make full use of insufficient information, we propose a DTI prediction model based on Dynamic Heterogeneous Graph (DT-DHG). And progressive learning is introduced to adjust the receptive fields of node. The experimental results show that our method significantly improves the performance of the original GNNs and is robust against the choices of backbones. Meanwhile, DT-DHG outperforms the state-of-the-art methods and effectively predicts novel DTIs.

Exploring drug-target interaction prediction on cold-start scenarios via meta-learning-based graph transformer.

Predicting drug-target interaction (DTI) is of great importance for drug discovery and development. With the rapid development of biological and chemical technologies, computational methods for DTI prediction are becoming a promising approach. However, there are few solutions to the cold-start problem in DTI prediction scenarios, as these methods rely on existing interaction information to support their modeling. Consequently, they are unable to effectively predict DTIs for new drugs or targets with limited interaction data in the existing work. To this end, we propose a graph transformer method based on meta-learning named MGDTI (short for Meta-learning-based Graph Transformer for Drug-Target Interaction prediction) to fill this gap. Technically, we employ drug-drug similarity and target-target similarity as additional information to mitigate the scarcity of interactions. Besides, we trained MGDTI via meta-learning to be adaptive to cold-start tasks. Moreover, we employed graph transformer to prevent over-smoothing by capturing long-range dependencies. Extensive results on the benchmark dataset demonstrate that MGDTI is effective on DTI prediction under cold-start scenarios.

DMHGNN: Double multi-view heterogeneous graph neural network framework for drug-target interaction prediction

DMHGNN: Double multi-view heterogeneous graph neural network framework for drug-target interaction prediction

Multi-layer graph attention neural networks for accurate drug-target interaction mapping

In the crucial process of drug discovery and repurposing, precise prediction of drug-target interactions (DTIs) is paramount. This study introduces a novel DTI prediction approach—Multi-Layer Graph Attention Neural Network (MLGANN), through a groundbreaking computational framework that effectively harnesses multi-source information to enhance prediction accuracy. MLGANN not only strides forward in constructing a multi-layer DTI network by capturing both direct interactions between drugs and targets as well as their multi-level information but also amalgamates Graph Convolutional Networks (GCN) with a self-attention mechanism to comprehensively integrate diverse data sources. This method exhibited significant performance surpassing existing approaches in comparative experiments, underscoring its immense potential in elevating the efficiency and accuracy of DTI predictions. More importantly, this study accentuates the significance of considering multi-source data information and network heterogeneity in the drug discovery process, offering new perspectives and tools for future pharmaceutical research.

Enhancing drug-target interaction predictions in context of neurodegenerative diseases using bidirectional long short-term memory in male Swiss albino mice pharmaco-EEG analysis

Background and ObjectiveEmerging diseases like Parkinson or Alzheimer's, which are not curable, endanger human mental health and are challenging to research. Drug target interactions (DTI) are pivotal in the screening of candidate drugs and focus on a small pool of drug targets. Electroencephalogram shows the responses to psychotropic medicines in the brain bioelectric activity. Synaptic activity can be analyzed by using Local Field Potential recordings obtained from micro-electrodes implanted in the brain. The aim is to evaluate the effects of drug on brain bioelectric activity and increase the drug classification accuracy. The ultimate goal is to advance our understanding of how drugs affect synaptic activity and open the door to more focused treatment for neurodegenerative diseases. MethodsIn this study, Pharmaco-EEG recordings are processed using Advanced neural network models, particularly Convolutional Neural Networks, to assess the effects of medications. The five different medicines used in this study are Ephedrine, Fluoxetine, Kratom, Morphine, and Saline. The signals observed are local field potential signals. To overcome some limits of DTI prediction, we propose Bidirectional Long Short-Term Memory (LSTM) for the categorization of intracranial EEG (i-EEG) data, departing from standard approaches. Similar EEG patterns are presumably caused by drugs that work by homologous pharmacological pathways, producing similar psychotropic effects. To improve accuracy and reduce training loss, our study introduces a bidirectional LSTM model for classification along with Bayesian optimization ResultsHigh recall, precision, and F1-Scores, particularly a 95% F1-Score for morphine, ephedrine, fluoxetine, and saline, suggest good performance in predicting these drug classes. Kratom produces a somewhat lower recall of 94%, but a high F1-Score of 97% and perfect precision of 1.00. The weighted average F1-Score, macro average, and overall accuracy are all consistently high (around 97%), indicating that the model works well throughout the spectrum of drugs. ConclusionsImproved model performance was demonstrated by using a diversified dataset with five drug categories and bidirectional LSTM boosted with Bayesian optimization for hyperparameter tuning. From earlier limited-category models, it represents a substantial advancement.

Accurate prediction of drug-target interactions in Chinese and western medicine by the CWI-DTI model

Accurate prediction of drug-target interactions (DTIs) is crucial for advancing drug discovery and repurposing. Computational methods have significantly improved the efficiency of experimental predictions for drug-target interactions in Western medicine. However, accurately predicting the complex relationships between Chinese medicine ingredients and targets remains a formidable challenge due to the vast number and high heterogeneity of these ingredients. In this study, we introduce the CWI-DTI method, which achieves high-accuracy prediction of DTIs using a large dataset of interactive relationships of drug ingredients or candidate targets. Moreover, we present a novel dataset to evaluate the prediction accuracy of both Chinese and Western medicine. Through meticulous collection and preprocessing of data on ingredients and targets, we employ an innovative autoencoder framework to fuse multiple drug (target) topological similarity matrices. Additionally, we employ denoising blocks, sparse blocks, and stacked blocks to extract crucial features from the similarity matrix, reducing noise and enhancing accuracy across diverse datasets. Our results indicate that the CWI-DTI model shows improved performance compared to several existing state-of-the-art methods on the datasets tested in both Western and Chinese medicine databases. The findings of this study hold immense promise for advancing DTI prediction in Chinese and Western medicine, thus fostering more efficient drug discovery and repurposing endeavors. Our model is available at https://github.com/WANG-BIN-LAB/CWIDTI.

Drug–target prediction through self supervised learning with dual task ensemble approach

Drug–Target interaction (DTI) prediction, a transformative approach in pharmaceutical research, seeks novel therapeutic applications for computational method based virtual screening, existing drugs to address untreated diseases and discovery of existing drugs side effects. The proposed model predict DTI through Heterogeneous biological network by combining drug, genes and disease related knowledge. For the purpose of embedding extraction Self-supervised learning (SSL) has been used which, trains models through pretext tasks, eliminating the need for manual annotations. The pretext tasks are related to either structural based information or similarity based information. To mitigate GNN vulnerability to non-robustness, ensemble learning can be incorporated into GNNs, harnessing multiple models to enhance robustness. This paper introduces a Graph neural network based architecture consisting of task based module and ensemble module for link prediction of DTI. The ensemble module of dual task combinations, both in cold start and warm start scenarios achieve very good performance as it provide 0.960 in cold start and 0.970 in warm start mean AUCROC score with less deviation.

DrugReAlign: a multisource prompt framework for drug repurposing based on large language models.

Drug repurposing is a promising approach in the field of drug discovery owing to its efficiency and cost-effectiveness. Most current drug repurposing models rely on specific datasets for training, which limits their predictive accuracy and scope. The number of both market-approved and experimental drugs is vast, forming an extensive molecular space. Due to limitations in parameter size and data volume, traditional drug-target interaction (DTI) prediction models struggle to generalize well within such a broad space. In contrast, large language models (LLMs), with their vast parameter sizes and extensive training data, demonstrate certain advantages in drug repurposing tasks. In our research, we introduce a novel drug repurposing framework, DrugReAlign, based on LLMs and multi-source prompt techniques, designed to fully exploit the potential of existing drugs efficiently. Leveraging LLMs, the DrugReAlign framework acquires general knowledge about targets and drugs from extensive human knowledge bases, overcoming the data availability limitations of traditional approaches. Furthermore, we collected target summaries and target-drug space interaction data from databases as multi-source prompts, substantially improving LLM performance in drug repurposing. We validated the efficiency and reliability of the proposed framework through molecular docking and DTI datasets. Significantly, our findings suggest a direct correlation between the accuracy of LLMs' target analysis and the quality of prediction outcomes. These findings signify that the proposed framework holds the promise of inaugurating a new paradigm in drug repurposing.

MGACL: Prediction Drug-Protein Interaction Based on Meta-Graph Association-Aware Contrastive Learning.

The identification of drug-target interaction (DTI) is crucial for drug discovery. However, how to reduce the graph neural network's false positives due to its bias and negative transfer in the original bipartite graph remains to be clarified. Considering that the impact of heterogeneous auxiliary information on DTI varies depending on the drug and target, we established an adaptive enhanced personalized meta-knowledge transfer network named Meta Graph Association-Aware Contrastive Learning (MGACL), which can transfer personalized heterogeneous auxiliary information from different nodes and reduce data bias. Meanwhile, we propose a novel DTI association-aware contrastive learning strategy that aligns high-frequency drug representations with learned auxiliary graph representations to prevent negative transfer. Our study improves the DTI prediction performance by about 3%, evaluated by analyzing the area under the curve (AUC) and area under the precision-recall curve (AUPRC) compared with existing methods, which is more conducive to accurately identifying drug targets for the development of new drugs.

TC-DTA: Predicting Drug-Target Binding Affinity With Transformer and Convolutional Neural Networks.

Bioinformatics is a rapidly evolving field that applies computational methods to analyze and interpret biological data. A key task in bioinformatics is identifying novel drug-target interactions (DTIs), which plays a crucial role in drug discovery. Most computational approaches treat DTI prediction as a binary classification problem, determining whether drug-target pairs interact. However, with the growing availability of drug-target binding affinity data, this binary task can be reframed as a regression problem focused on drug-target affinity (DTA). DTA quantifies the strength of drug-target binding, offering more detailed insights than DTI and serving as a valuable tool for virtual screening in drug discovery. Accurately predicting compound interactions with targets can accelerate the drug development process. In this study, we introduce a deep learning model named TC-DTA for DTA prediction, leveraging convolutional neural networks (CNN) and the encoder module of the transformer architecture. We begin by extracting raw drug SMILES strings and protein amino acid sequences from the dataset, which are then represented using various encoding methods. Subsequently, we employ CNN and the transformer's encoder module to extract features from the drug SMILES strings and protein sequences, respectively. Finally, the feature information is concatenated and input into a multi-layer perceptron to predict binding affinity scores. We evaluated our model on two benchmark DTA datasets, Davis and KIBA, comparing it with methods such as KronRLS, SimBoost, and DeepDTA. Our model, TC-DTA, outperformed these baseline methods based on evaluation metrics like Mean Squared Error (MSE), Concordance Index (CI), and Regression towards the Mean Index ( rm2 ). These results highlight the effectiveness of the Transformer's encoder and CNN in extracting meaningful representations from sequences, thereby enhancing DTA prediction accuracy. This deep learning model can accelerate drug discovery by identifying drug candidates with high binding affinity to specific targets. Compared to traditional methods, machine learning technology offers a more effective and efficient approach to drug discovery.

Drug-target interaction prediction with collaborative contrastive learning and adaptive self-paced sampling strategy

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.

DRADTiP: Drug repurposing for aging disease through drug-target interaction prediction

MotivationThe greatest risk factor for many non-communicable diseases is aging. Studies on model organisms have demonstrated that genetic and chemical perturbation alterations can lengthen longevity and overall health. However, finding longevity-enhancing medications and their related targets is difficult. MethodIn this work, we designed a novel drug repurposing model by identifying the interaction between aging-related genes or targets and drugs similar to aging disease. Each disease is associated with certain specific genetic factors for the occurrence of that disease. The factors include gene expression, pathway, miRNA, and degree of genes in the protein-protein interaction network. In this paper, we aim to find the drugs that prolong the life span of humans with their aging-related targets using the above-mentioned factors. In addition, the contribution or importance of each factor may vary among drugs and targets. Therefore, we designed a novel multi-layer random walk-based network representation learning model including node and edge weight to learn the features of drugs and targets respectively. ResultThe performance of the proposed model is demonstrated using k-fold cross-validation (k = 5). This model achieved better performance with scores of 0.93 and 0.91 for precision and recall respectively. The drugs identified by the system are evaluated to be potential candidates for aging since the degree of interaction between the potential drugs and their gene sets are high. In addition, the genes that are interacting with drugs produce the same biological functions. Hence the life span of the human will be increased or prolonged.

Improving Drug-Target Interaction Prediction through Dual-Modality Fusion with InteractNet

Improving Drug-Target Interaction Prediction through Dual-Modality Fusion with InteractNet

GIAE-DTI: Predicting Drug-Target Interactions Based on Heterogeneous Network and GIN-based Graph Autoencoder.

Accurate prediction of drug-target interactions (DTIs) is essential for advancing drug discovery and repurposing. However, the sparsity of DTI data limits the effectiveness of existing computational methods, which primarily focus on sparse DTI networks and have poor performance in aggregating information from neighboring nodes and representing isolated nodes within the network. In this study, we propose a novel deep learning framework, named GIAE-DTI, which considers cross-modal similarity of drugs and targets and constructs a heterogeneous network for DTI prediction. Firstly, the model calculates the cross-modal similarity of drugs and proteins from the relationships among drugs, proteins, diseases, and side effects, and performs similarity integration by taking the average. Then, a drug-target heterogeneous network is constructed, including drug-drug interactions, protein-protein interactions, and drug-target interactions processed by weighted K nearest known neighbors. In the heterogeneous network, a graph autoencoder based on a graph isomorphism network is employed for feature extraction, while a dual decoder is utilized to achieve better self-supervised learning, resulting in latent feature representations for drugs and targets. Finally, a deep neural network is employed to predict DTIs. The experimental results indicate that on the benchmark dataset, GIAE-DTI achieves AUC and AUPR scores of 0.9533 and 0.9619, respectively, in DTI prediction, outperforming the current state-of-the-art methods. Additionally, case studies on four 5-hydroxytryptamine receptor-related targets and five drugs related to mental diseases show the great potential of the proposed method in practical applications.

DTI-LM: language model powered drug-target interaction prediction.

The identification and understanding of drug-target interactions (DTIs) play a pivotal role in the drug discovery and development process. Sequence representations of drugs and proteins in computational model offer advantages such as their widespread availability, easier input quality control, and reduced computational resource requirements. These make them an efficient and accessible tools for various computational biology and drug discovery applications. Many sequence-based DTI prediction methods have been developed over the years. Despite the advancement in methodology, cold start DTI prediction involving unknown drug or protein remains a challenging task, particularly for sequence-based models. Introducing DTI-LM, a novel framework leveraging advanced pretrained language models, we harness their exceptional context-capturing abilities along with neighborhood information to predict DTIs. DTI-LM is specifically designed to rely solely on sequence representations for drugs and proteins, aiming to bridge the gap between warm start and cold start predictions. Large-scale experiments on four datasets show that DTI-LM can achieve state-of-the-art performance on DTI predictions. Notably, it excels in overcoming the common challenges faced by sequence-based models in cold start predictions for proteins, yielding impressive results. The incorporation of neighborhood information through a graph attention network further enhances prediction accuracy. Nevertheless, a disparity persists between cold start predictions for proteins and drugs. A detailed examination of DTI-LM reveals that language models exhibit contrasting capabilities in capturing similarities between drugs and proteins. Source code is available at: https://github.com/compbiolabucf/DTI-LM.

HEnsem_DTIs: A heterogeneous ensemble learning model for drug-target interactions prediction

Drug discovery is the process by which a drug is discovered. Drug-target interactions prediction is a major part of drug discovery. Unfortunately, producing new drugs is time-consuming and expensive; Because it requires a lot of human and laboratory resources. Recently, predictions have been made using computational methods to solve these problems and prevent blindly examining all interactions. Various experiences using computational methods show that no single algorithm can be suitable for all applications; Hence, ensemble learning is expressed. Although various ensemble methods have been proposed, it is still not easy to find a suitable ensemble method for a particular dataset. In general, the existing algorithms in aggregation and combination method are selected manually based on experience. Reinforcement learning can be one way to meet this challenge. High-dimensional feature space and class imbalance are among the challenges of drug-target interactions prediction. This paper proposes HEnsem_DTIs, a heterogeneous ensemble model, for predicting drug-target interactions using dimensionality reduction and concepts of recommender systems to address these challenges. HEnsem_DTIs is configured with reinforcement learning. Dimensionality reduction is applied to handle the challenge of high-dimensional feature space and recommender systems to improve under-sampling and solve the class imbalance challenge. Six datasets are used to evaluate the proposed model; Results of the evaluation on datasets show that HEnsem_DTIs works better than other models in this field. Results of evaluation of the proposed model on the first dataset using 10-fold cross-validation experiments show the amount of sensitivity 0.896, specificity 0.954, GM 0.924, AUC 0.930 and AUPR 0.935.

A pseudo-label supervised graph fusion attention network for drug–target interaction prediction

Drug–target interaction (DTI) prediction can reveal new drug targets and assist in drug repositioning. It can also help identify the most potential candidate drugs for specific targets, advancing new drug discovery. Graph Convolutional Networks (GCNs) have been employed to explore potential relationships between drug–target pairs (DTPs) due to their strong learning capabilities. However, existing methods primarily rely on static graphs constructed from topological structures. These graphs may contain missing or meaningless edges, limiting the ability of GCNs to capture node embeddings. Furthermore, the lack of labels in practical DTI prediction presents a significant challenge. To address these issues, this paper introduces a pseudo-label supervised graph fusion attention network for DTI prediction (PSF-DTI). Specifically, we establish a far-neighbor graph to capture robust differential information between DTPs, compensating for the limitations of traditional topology graphs. Additionally, we create an adaptive graph to dynamically update edge information for more accurate graph structures. During training, we assign pseudo-labels to unlabeled data based on feature similarities between DTPs, mitigating the impact of label scarcity. Comparative experiments with seven state-of-the-art algorithms on public datasets demonstrate the superior performance of PSF-DTI. Extensive ablation experiments validate the effectiveness of the proposed approaches. Our findings suggest that PSF-DTI offers significant advantages in DTI prediction, providing innovative methods and perspectives for future drug discovery and repositioning.

Predicting drug-target interactions by measuring confidence with consistent causal neighborhood interventions

Predicting drug-target interactions (DTI) is a crucial stage in drug discovery and development. Understanding the interaction between drugs and targets is essential for pinpointing the specific relationship between drug molecules and targets, akin to solving a link prediction problem using information technology. While knowledge graph (KG) and knowledge graph embedding (KGE) methods have been rapid advancements and demonstrated impressive performance in drug discovery, they often lack authenticity and accuracy in identifying DTI. This leads to increased misjudgment rates and reduced efficiency in drug development. To address these challenges, our focus lies in refining the accuracy of DTI prediction models through KGE, with a specific emphasis on causal intervention confidence measures (CI). These measures aim to assess triplet scores, enhancing the precision of the predictions. Comparative experiments conducted on three datasets and utilizing 9 KGE models reveal that our proposed confidence measure approach via causal intervention, significantly improves the accuracy of DTI link prediction compared to traditional approaches. Furthermore, our experimental analysis delves deeper into the embedding of intervention values, offering valuable insights for guiding the design and development of subsequent drug development experiments. As a result, our predicted outcomes serve as valuable guidance in the pursuit of more efficient drug development processes.