Current Bioinformatics - Volume 19, Issue 8, 2024

Background: This study addresses the need for analyzing viral genome sequences and understanding their genetic relationships. The focus is on introducing a novel natural graph approach as a solution. Objective: The objective of this study is to demonstrate the effectiveness and advantages of the proposed natural graph approach in clustering viral genome sequences into distinct clades, subtypes, or districts. Additionally, the aim is to explore its interpretability, potential applications, and implications for pandemic control and public health interventions. Methods: The study utilizes the proposed natural graph algorithm to cluster viral genome sequences. The results are compared with existing methods and multidimensional scaling to evaluate the performance and effectiveness of the approach. Results: The natural graph approach successfully clusters viral genome sequences, providing valuable insights into viral evolution and transmission dynamics. The ability to generate directed connections between nodes enhances the interpretability of the results, facilitating the investigation of transmission pathways and viral fitness. Conclusion: The findings highlight the potential applications of the natural graph algorithm in pandemic control, transmission tracing, and vaccine design. Future research directions may involve scaling up the analysis to larger datasets and incorporating additional genetic features for improved resolution. The natural graph approach presents a promising tool for viral genomics research with implications for public health interventions.

Background: Numerous studies have shown that mitochondrial damage induces inflammation and activates inflammatory cells, leading to sepsis, while sepsis, a systemic inflammatory response syndrome, also exacerbates mitochondrial damage and hyperactivation. Mitochondrial autophagy eliminates aged, abnormal or damaged mitochondria to reduce intracellular mitochondrial stress and the release of mitochondria-associated molecules, thereby reducing the inflammatory response and cellular damage caused by sepsis. In addition, mitochondrial autophagy may also influence the onset and progression of sepsis, but the exact mechanisms are unclear. Methods: In this study, we mined the available publicly available microarray data in the GEO database (Home - GEO - NCBI (nih.gov)) with the aim of identifying key genes associated with mitochondrial autophagy in sepsis. Results: We identified four mitophagy-related genes in sepsis, TOMM20, TOMM22, TOMM40, and MFN1. Conclusion: This study provides preliminary evidence for the treatment of sepsis and may provide a solid foundation for subsequent biological studies.

Background: With new variants of COVID-19 causing challenges, we need to focus on integrating multiple deep-learning frameworks to develop intelligent healthcare systems for early detection and diagnosis. Objective: This article suggests three hybrid deep learning models, namely CNN-LSTM, CNN-Bi- LSTM, and CNN-GRU, to address the pressing need for an intelligent healthcare system. These models are designed to capture spatial and temporal patterns in COVID-19 data, thereby improving the accuracy and timeliness of predictions. An output forecasting framework integrates these models, and an optimization algorithm automatically selects the hyperparameters for the 13 baselines and the three proposed hybrid models. Methods: Real-time time series data from the five most affected countries were used to test the effectiveness of the proposed models. Baseline models were compared, and optimization algorithms were employed to improve forecasting capabilities. Results: CNN-GRU and CNN-LSTM are the top short- and long-term forecasting models. CNNGRU had the best performance with the lowest SMAPE and MAPE values for long-term forecasting in India at 3.07% and 3.17%, respectively, and impressive results for short-term forecasting with SMAPE and MAPE values of 1.46% and 1.47%. Conclusion: Hybrid deep learning models, like CNN-GRU, can aid in early COVID-19 assessment and diagnosis. They detect patterns in data for effective governmental strategies and forecasting. This helps manage and mitigate the pandemic faster and more accurately.

Background: With increasing rates of polypharmacy, the vigilant surveillance of clinical drug toxicity has emerged as an important concern. Named Entity Recognition (NER) stands as an indispensable undertaking, essential for the extraction of valuable insights regarding drug safety from the biomedical literature. In recent years, significant advancements have been achieved in the deep learning models on NER tasks. Nonetheless, the effectiveness of these NER techniques relies on the availability of substantial volumes of annotated data, which is labor-intensive and inefficient. Methods: This study introduces a novel approach that diverges from the conventional reliance on manually annotated data. It employs a transformer-based technique known as Positive-Unlabeled Learning (PULearning), which incorporates adaptive learning and is applied to the clinical cancer drug toxicity corpus. To improve the precision of prediction, we employ relative position embeddings within the transformer encoder. Additionally, we formulate a composite loss function that integrates two Kullback-Leibler (KL) regularizers to align with PULearning assumptions. The outcomes demonstrate that our approach attains the targeted performance for NER tasks, solely relying on unlabeled data and named entity dictionaries. Conclusion: Our model achieves an overall NER performance with an F1 of 0.819. Specifically, it attains F1 of 0.841, 0.801 and 0.815 for DRUG, CANCER, and TOXI entities, respectively. A comprehensive analysis of the results validates the effectiveness of our approach in comparison to existing PULearning methods on biomedical NER tasks. Additionally, a visualization of the associations among three identified entities is provided, offering a valuable reference for querying their interrelationships.

Background: Time-course single-cell RNA sequencing (scRNA-seq) data represent dynamic gene expression values that change over time, which can be used to infer causal relationships between genes and construct dynamic gene regulatory networks (GRNs). However, most of the existing methods are designed for bulk RNA sequencing (bulk RNA-seq) data and static scRNA-seq data, and only a few methods, such as CNNC and DeepDRIM can be directly applied to time-course scRNA-seq data. Objective: This work aims to infer causal relationships between genes and construct dynamic gene regulatory networks using time-course scRNA-seq data. Methods: We propose an analytical method for inferring GRNs from single-cell time-course data based on temporal convolutional networks (scTGRN), which provides a supervised learning approach to infer causal relationships among genes. scTGRN constructs a 4D tensor representing gene expression features for each gene pair, then inputs the constructed 4D tensor into the temporal convolutional network to train and infer the causal relationship between genes. Results: We validate the performance of scTGRN on five real datasets and four simulated datasets, and the experimental results show that scTGRN outperforms existing models in constructing GRNs. In addition, we test the performance of scTGRN on gene function assignment, and scTGRN outperforms other models. Conclusion: The analysis shows that scTGRN can not only accurately identify the causal relationship between genes, but also can be used to achieve gene function assignment.

Introduction: Transcriptional gene expressions and their corresponding spatial information are critical for understanding the biological function, mutual regulation, and identification of various cell types. Materials and Methods: Recently, several computational methods have been proposed for clustering using spatial transcriptional expression. Although these algorithms have certain practicability, they cannot utilize spatial information effectively and are highly sensitive to noise and outliers. In this study, we propose ACSpot, an autoencoder-based fuzzy clustering algorithm, as a solution to tackle these problems. Specifically, we employed a self-supervised autoencoder to reduce feature dimensionality, mitigate nonlinear noise, and learn high-quality representations. Additionally, a commonly used clustering method, Fuzzy c-means, is used to achieve improved clustering results. In particular, we utilize spatial neighbor information to optimize the clustering process and to fine-tune each spot to its associated cluster category using probabilistic and statistical methods. Result and Discussion: The comparative analysis on the 10x Visium human dorsolateral prefrontal cortex (DLPFC) dataset demonstrates that ACSpot outperforms other clustering algorithms. Subsequently, spatially variable genes were identified based on the clustering outcomes, revealing a striking similarity between their spatial distribution and the subcluster spatial distribution from the clustering results. Notably, these spatially variable genes include APP, PSEN1, APOE, SORL1, BIN1, and PICALM, all of which are well-known Alzheimer's disease-associated genes. Conclusion: In addition, we applied our model to explore some potential Alzheimer's disease correlated genes within the dataset and performed Gene Ontology (GO) enrichment and gene-pathway analyses for validation, illustrating the capability of our model to pinpoint genes linked to Alzheimer's disease.

Background: Comparing directed networks using the alignment-free technique offers the advantage of detecting topologically similar regions that are independent of the network size or node identity. Objective: We propose a novel method to compare directed networks by decomposing the network into small modules, the so-called network subgraph approach, which is distinct from the network motif approach because it does not depend on null model assumptions. Method: We developed an alignment-free algorithm called the Subgraph Identification Algorithm (SIA, which could generate all subgraphs that have five connected nodes (5-node subgraph). There were 9,364 such modules. Then, we applied the SIA method to examine 17 cancer networks and measured the similarity between the two networks by gauging the similarity level using Jensen-Shannon entropy (HJS). Results: We identified and examined the biological meaning of 5-node regulatory modules and pairs of cancer networks with the smallest HJS values. The two pairs of networks that show similar patterns are (i) endometrial cancer and hepatocellular carcinoma and (ii) breast cancer and pathways in cancer. Some studies have provided experimental data supporting the 5-node regulatory modules. Conclusion: Our method is an alignment-free approach that measures the topological similarity of 5-node regulatory modules and aligns two directed networks based on their topology. These modules capture complex interactions among multiple genes that cannot be detected using existing methods that only consider single-gene relations. We analyzed the biological relevance of the regulatory modules and used the subgraph method to identify the modules that shared the same topology across 2 cancer networks out of 17 cancer networks. We validated our findings using evidence from the literature.