HTINet2: herb–target prediction via knowledge graph embedding and residual-like graph neural network
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PROVIDER: S-EPMC11341278 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecent advances in simultaneous measurement of RNA and protein abundances at single-cell level provide a unique opportunity to predict protein abundance from scRNA-seq data using machine learning models. However, existing machine learning methods have not considered relationship among the proteins sufficiently.ResultsWe formulate this task in a multi-label prediction framework where multiple proteins are linked to each other at the single-cell level. Then, we propose a novel method for single-cell RNA to protein prediction named PIKE-R2P, which incorporates protein-protein interactions (PPI) and prior knowledge embedding into a graph neural network. Compared with existing methods, PIKE-R2P could significantly improve prediction performance in terms of smaller errors and higher correlations with the gold standard measurements.ConclusionThe superior performance of PIKE-R2P indicates that adding the prior knowledge of PPI to graph neural networks can be a powerful strategy for cross-modality prediction of protein abundances at the single-cell level.
| S-EPMC8170782 | biostudies-literature
Project description:Protein-protein interactions (PPIs) are essential for most biological processes. However, current PPI networks present high levels of noise, sparseness and incompleteness, which limits our ability to understand the cell at the system level from the PPI network. Predicting novel (missing) links in noisy PPI networks is an essential computational method for automatically expanding the human interactome and for identifying biologically legitimate but undetected interactions for experimental determination of PPIs, which is both expensive and time-consuming. Recently, graph convolutional networks (GCN) have shown their effectiveness in modeling graph-structured data, which employ a 1-hop neighborhood aggregation procedure and have emerged as a powerful architecture for node or graph representations. In this paper, we propose a novel node (protein) embedding method by combining GCN and PageRank as the latter can significantly improve the GCN's aggregation scheme, which has difficulty in extending and exploring topological information of networks across higher-order neighborhoods of each node. Building on this novel node embedding model, we develop a higher-order GCN variational auto-encoder (HO-VGAE) architecture, which can learn a joint node representation of higher-order local and global PPI network topology for novel protein interaction prediction. It is worth noting that our method is based exclusively on network topology, with no protein attributes or extra biological features used. Extensive computational validations on PPI prediction task demonstrate our method without leveraging any additional biological information shows competitive performance-outperforms all existing graph embedding-based link prediction methods in both accuracy and robustness.
| S-EPMC7514053 | biostudies-literature
Project description:BackgroundThe pharmaceutical field faces a significant challenge in validating drug target interactions (DTIs) due to the time and cost involved, leading to only a fraction being experimentally verified. To expedite drug discovery, accurate computational methods are essential for predicting potential interactions. Recently, machine learning techniques, particularly graph-based methods, have gained prominence. These methods utilize networks of drugs and targets, employing knowledge graph embedding (KGE) to represent structured information from knowledge graphs in a continuous vector space. This phenomenon highlights the growing inclination to utilize graph topologies as a means to improve the precision of predicting DTIs, hence addressing the pressing requirement for effective computational methodologies in the field of drug discovery.ResultsThe present study presents a novel approach called DTIOG for the prediction of DTIs. The methodology employed in this study involves the utilization of a KGE strategy, together with the incorporation of contextual information obtained from protein sequences. More specifically, the study makes use of Protein Bidirectional Encoder Representations from Transformers (ProtBERT) for this purpose. DTIOG utilizes a two-step process to compute embedding vectors using KGE techniques. Additionally, it employs ProtBERT to determine target-target similarity. Different similarity measures, such as Cosine similarity or Euclidean distance, are utilized in the prediction procedure. In addition to the contextual embedding, the proposed unique approach incorporates local representations obtained from the Simplified Molecular Input Line Entry Specification (SMILES) of drugs and the amino acid sequences of protein targets.ConclusionsThe effectiveness of the proposed approach was assessed through extensive experimentation on datasets pertaining to Enzymes, Ion Channels, and G-protein-coupled Receptors. The remarkable efficacy of DTIOG was showcased through the utilization of diverse similarity measures in order to calculate the similarities between drugs and targets. The combination of these factors, along with the incorporation of various classifiers, enabled the model to outperform existing algorithms in its ability to predict DTIs. The consistent observation of this advantage across all datasets underlines the robustness and accuracy of DTIOG in the domain of DTIs. Additionally, our case study suggests that the DTIOG can serve as a valuable tool for discovering new DTIs.
| S-EPMC10731821 | biostudies-literature
Project description:AI-driven approaches are widely used in drug discovery, where candidate molecules are generated and tested on a target protein for binding affinity prediction. However, generating new compounds with desirable molecular properties such as Quantitative Estimate of Drug-likeness (QED) and Dopamine Receptor D2 activity (DRD2) while adhering to distinct chemical laws is challenging. To address these challenges, we proposed a graph-based deep learning framework to generate potential therapeutic drugs targeting the SARS-CoV-2 protein. Our proposed framework consists of two modules: a novel reinforcement learning (RL)-based graph generative module with knowledge graph (KG) and a graph early fusion approach (GEFA) for binding affinity prediction. The first module uses a gated graph neural network (GGNN) model under the RL environment for generating novel molecular compounds with desired properties and a custom-made KG for molecule screening. The second module uses GEFA to predict binding affinity scores between the generated compounds and target proteins. Experiments show how fine-tuning the GGNN model under the RL environment enhances the molecules with desired properties to generate 100% valid and 100% unique compounds using different scoring functions. Additionally, KG-based screening reduces the search space of generated candidate molecules by 96.64% while retaining 95.38% of promising binding molecules against SARS-CoV-2 protein, i.e., 3C-like protease (3CLpro). We achieved a binding affinity score of 8.185 from the top rank of generated compound. In addition, we compared top-ranked generated compounds to Indinavir on different parameters, including drug-likeness and medicinal chemistry, for qualitative analysis from a drug development perspective.Supplementary informationThe online version contains supplementary material available at 10.1007/s13721-023-00409-2.
| S-EPMC9817447 | biostudies-literature
Project description: Not available
| S-EPMC11373278 | biostudies-literature
Project description:The identification of drug-target interaction (DTI) plays a key role in drug discovery and development. Benefitting from large-scale drug databases and verified DTI relationships, a lot of machine-learning methods have been developed to predict DTIs. However, due to the difficulty in extracting useful information from molecules, the performance of these methods is limited by the representation of drugs and target proteins. This study proposes a new model called EmbedDTI to enhance the representation of both drugs and target proteins, and improve the performance of DTI prediction. For protein sequences, we leverage language modeling for pretraining the feature embeddings of amino acids and feed them to a convolutional neural network model for further representation learning. For drugs, we build two levels of graphs to represent compound structural information, namely the atom graph and substructure graph, and adopt graph convolutional network with an attention module to learn the embedding vectors for the graphs. We compare EmbedDTI with the existing DTI predictors on two benchmark datasets. The experimental results show that EmbedDTI outperforms the state-of-the-art models, and the attention module can identify the components crucial for DTIs in compounds.
| S-EPMC8698792 | biostudies-literature
Project description:BackgroundAs many interactions between the chemical and genomic space remain undiscovered, computational methods able to identify potential drug-target interactions (DTIs) are employed to accelerate drug discovery and reduce the required cost. Predicting new DTIs can leverage drug repurposing by identifying new targets for approved drugs. However, developing an accurate computational framework that can efficiently incorporate chemical and genomic spaces remains extremely demanding. A key issue is that most DTI predictions suffer from the lack of experimentally validated negative interactions or limited availability of target 3D structures.ResultsWe report DT2Vec, a pipeline for DTI prediction based on graph embedding and gradient boosted tree classification. It maps drug-drug and protein-protein similarity networks to low-dimensional features and the DTI prediction is formulated as binary classification based on a strategy of concatenating the drug and target embedding vectors as input features. DT2Vec was compared with three top-performing graph similarity-based algorithms on a standard benchmark dataset and achieved competitive results. In order to explore credible novel DTIs, the model was applied to data from the ChEMBL repository that contain experimentally validated positive and negative interactions which yield a strong predictive model. Then, the developed model was applied to all possible unknown DTIs to predict new interactions. The applicability of DT2Vec as an effective method for drug repurposing is discussed through case studies and evaluation of some novel DTI predictions is undertaken using molecular docking.ConclusionsThe proposed method was able to integrate and map chemical and genomic space into low-dimensional dense vectors and showed promising results in predicting novel DTIs.
| S-EPMC8978405 | biostudies-literature
Project description:In silico prediction of drug-target interactions is a critical phase in the sustainable drug development process, especially when the research focus is to capitalize on the repositioning of existing drugs. However, developing such computational methods is not an easy task, but is much needed, as current methods that predict potential drug-target interactions suffer from high false-positive rates. Here we introduce DTiGEMS+, a computational method that predicts Drug-Target interactions using Graph Embedding, graph Mining, and Similarity-based techniques. DTiGEMS+ combines similarity-based as well as feature-based approaches, and models the identification of novel drug-target interactions as a link prediction problem in a heterogeneous network. DTiGEMS+ constructs the heterogeneous network by augmenting the known drug-target interactions graph with two other complementary graphs namely: drug-drug similarity, target-target similarity. DTiGEMS+ combines different computational techniques to provide the final drug target prediction, these techniques include graph embeddings, graph mining, and machine learning. DTiGEMS+ integrates multiple drug-drug similarities and target-target similarities into the final heterogeneous graph construction after applying a similarity selection procedure as well as a similarity fusion algorithm. Using four benchmark datasets, we show DTiGEMS+ substantially improves prediction performance compared to other state-of-the-art in silico methods developed to predict of drug-target interactions by achieving the highest average AUPR across all datasets (0.92), which reduces the error rate by 33.3% relative to the second-best performing model in the state-of-the-art methods comparison.
| S-EPMC7325230 | biostudies-literature
Project description:Early detection of potential side effects (SE) is a critical and challenging task for drug discovery and patient care. In-vitro or in-vivo approach to detect potential SEs is not scalable for many drug candidates during the preclinical stage. Recent advances in explainable machine learning may facilitate detecting potential SEs of new drugs before market release and elucidating the critical mechanism of biological actions. Here, we leverage multi-modal interactions among molecules to develop a biologically informed graph-based SE prediction model, called HHAN-DSI. HHAN-DSI predicted frequent and even uncommon SEs of the unseen drug with higher or comparable accuracy against benchmark methods. When applying HHAN-DSI to the central nervous system, the organs with the largest number of SEs, the model revealed diverse psychiatric medications' previously unknown but probable SEs, together with the potential mechanisms of actions through a network of genes, biological functions, drugs, and SEs.
| S-EPMC10275013 | biostudies-literature
Project description:Computational methods play a pivotal role in the pursuit of efficient drug discovery, enabling the rapid assessment of compound properties before costly and time-consuming laboratory experiments. With the advent of technology and large data availability, machine and deep learning methods have proven efficient in predicting molecular solubility. High-precision in silico solubility prediction has revolutionized drug development by enhancing formulation design, guiding lead optimization, and predicting pharmacokinetic parameters. These benefits result in considerable cost and time savings, resulting in a more efficient and shortened drug development process. The proposed SolPredictor is designed with the aim of developing a computational model for solubility prediction. The model is based on residual graph neural network convolution (RGNN). The RGNNs were designed to capture long-range dependencies in graph-structured data. Residual connections enable information to be utilized over various layers, allowing the model to capture and preserve essential features and patterns scattered throughout the network. The two largest datasets available to date are compiled, and the model uses a simplified molecular-input line-entry system (SMILES) representation. SolPredictor uses the ten-fold split cross-validation Pearson correlation coefficient R2 0.79±0.02 and root mean square error (RMSE) 1.03±0.04. The proposed model was evaluated using five independent datasets. Error analysis, hyperparameter optimization analysis, and model explainability were used to determine the molecular features that were most valuable for prediction.
| S-EPMC10815788 | biostudies-literature