IEEE/ACM Transactions on Computational Biology and Bioinformatics最新文献

Due to their safety, high activity, and plentiful sources, antioxidant peptides, particularly those produced from food, are thought to be prospective competitors to synthetic antioxidants in the fight against free radical-mediated illnesses. The lengthy and laborious trial-and-error method for identifying antioxidative peptides (AOP) has raised interest in creating computational-based methods. There exist two state-of-the-art AOP predictors; however, the restriction on peptide sequence length makes them inviable. By overcoming the aforementioned problem, a novel predictor might be useful in the context of AOP prediction. The method has been trained, tested, and evaluated on two datasets: a balanced one and an unbalanced one. We used seven different descriptors and five machine-learning (ML) classifiers to construct 35 baseline models. Five ML classifiers were further trained to create five meta-models using the combined output of 35 baseline models. Finally, these five meta-models were aggregated together through ensemble learning to create a robust predictive model named iAnOxPep. On both datasets, our proposed model demonstrated good prediction performance when compared to baseline models and meta-models, demonstrating the superiority of our approach in the identification of AOPs. For the purpose of screening and identifying possible AOPs, we anticipate that the iAnOxPep method will be an invaluable tool.

The analysis of protein-ligand binding sites plays a crucial role in the initial stages of drug discovery. Accurately predicting the ligand types that are likely to bind to protein-ligand binding sites enables more informed decision making in drug design. Our study, DeepLigType, determines protein-ligand binding sites using Fpocket and then predicts the ligand type of these pockets with the deep learning model, Convolutional Block Attention Module (CBAM) with ResNet. CBAM-ResNet has been trained to accurately predict five distinct ligand types. We classified protein-ligand binding sites into five different categories according to the type of response ligands cause when they bind to their target proteins, which are antagonist, agonist, activator, inhibitor, and others. We created a novel dataset, referred to as LigType5, from the widely recognized PDBbind and scPDB dataset for training and testing our model. While the literature mostly focuses on the specificity and characteristic analysis of protein binding sites by experimental (laboratory-based) methods, we propose a computational method with the DeepLigType architecture. DeepLigType demonstrated an accuracy of 74.30% and an AUC of 0.83 in ligand type prediction on a novel test dataset using the CBAM-ResNet deep learning model.

The escalation of antibiotic resistance underscores the need for innovative approaches to combat bacterial infections. Phage therapy has emerged as a promising solution, wherein host determination plays an important role. Phage lysins, characterized by their specificity in targeting and cleaving corresponding host bacteria, serve as key players in this paradigm. In this study, we present a novel approach by leveraging genes of phage-encoded lytic enzymes for host prediction, culminating in the development of LHPre. Initially, gene fragments of phage-encoded lytic enzymes and their respective hosts were collected from the database. Second, DNA sequences were encoded using the Frequency Chaos Game Representation (FCGR) method, and pseudo samples were generated employing the Variational Autoencoder (VAE) model to address class imbalance. Finally, a prediction model was constructed using the Vision Transformer(Vit) model. Five-fold cross-validation results demonstrated that LHPre surpassed other state-of-the-art phage host prediction methods, achieving accuracies of 85.04%, 90.01%, and 93.39% at the species, genus, and family levels, respectively.

Recent advancements in generative models have established state-of-the-art benchmarks in the generation of molecules and novel drug candidates. Despite these successes, a significant gap persists between generative models and the utilization of extensive biomedical knowledge, often systematized within knowledge graphs, whose potential to inform and enhance generative processes has not been realized. In this paper, we present a novel approach that bridges this divide by developing a framework for knowledge-enhanced generative models called KARL. We develop a scalable methodology to extend the functionality of knowledge graphs while preserving semantic integrity, and incorporate this contextual information into a generative framework to guide a diffusion-based model. The integration of knowledge graph embeddings with our generative model furnishes a robust mechanism for producing novel drug candidates possessing specific characteristics while ensuring validity and synthesizability. KARL outperforms state-of-the-art generative models on both unconditional and targeted generation tasks.

Single cell RNA sequencing (scRNA-seq) is a powerful tool to capture gene expression snapshots in individual cells. However, a low amount of RNA in the individual cells results in dropout events, which introduce huge zero counts in the single cell expression matrix. We have developed VAImpute, a variational graph autoencoder based imputation technique that learns the inherent distribution of a large network/graph constructed from the scRNA-seq data leveraging copula correlation ($Ccor$) among cells/genes. The trained model is utilized to predict the dropouts events by computing the probability of all non-edges (cell-gene) in the network. We devise an algorithm to impute the missing expression values of the detected dropouts. The performance of the proposed model is assessed on both simulated and real scRNA-seq datasets, comparing it to established single-cell imputation methods. VAImpute yields significant improvements to detect dropouts, thereby achieving superior performance in cell clustering, detecting rare cells, and differential expression.