N6-methyladenosine (mA) plays a crucial regulatory role in the control of cellular functions and gene expression. Recent advances in sequencing techniques for transcriptome-wide mA mapping have accelerated the accumulation of mA site information at a single-nucleotide level, providing more high-confidence training data to develop computational approaches for mA site prediction. However, it is still a major challenge to precisely predict mA sites using in silico approaches.
View Article and Find Full Text PDFAdvances in single-cell transcriptomics provide an unprecedented opportunity to explore complex biological processes. However, computational methods for analyzing single-cell transcriptomics still have room for improvement especially in dimension reduction, cell clustering, and cell-cell communication inference. Herein, we propose a versatile method, named DcjComm, for comprehensive analysis of single-cell transcriptomics.
View Article and Find Full Text PDFCirculating tumor cells (CTCs) that undergo epithelial-to-mesenchymal transition (EMT) can provide valuable information regarding metastasis and potential therapies. However, current studies on the EMT overlook alternative splicing. Here, we used single-cell full-length transcriptome data and mRNA sequencing of CTCs to identify stage-specific alternative splicing of partial EMT and mesenchymal states during pancreatic cancer metastasis.
View Article and Find Full Text PDFN4-acetylcytidine (ac4C) is a modification of cytidine at the nitrogen-4 position, playing a significant role in the translation process of mRNA. However, the precise mechanism and details of how ac4C modifies translated mRNA remain unclear. Since identifying ac4C sites using conventional experimental methods is both labor-intensive and time-consuming, there is an urgent need for a method that can promptly recognize ac4C sites.
View Article and Find Full Text PDFUnexpected side effects may accompany the research stage and post-marketing of drugs. These accidents lead to drug development failure and even endanger patients' health. Thus, it is essential to recognize the unknown drug-side effects.
View Article and Find Full Text PDFMalignancies such as bladder urothelial carcinoma, colon adenocarcinoma, liver hepatocellular carcinoma, lung adenocarcinoma and prostate adenocarcinoma significantly impact men's well-being. Accurate cancer classification is vital in determining treatment strategies and improving patient prognosis. This study introduced an innovative method that utilizes gene selection from high-dimensional datasets to enhance the performance of the male tumor classification algorithm.
View Article and Find Full Text PDFMotivation: Cell-cell interactions (CCIs) play critical roles in many biological processes such as cellular differentiation, tissue homeostasis, and immune response. With the rapid development of high throughput single-cell RNA sequencing (scRNA-seq) technologies, it is of high importance to identify CCIs from the ever-increasing scRNA-seq data. However, limited by the algorithmic constraints, current computational methods based on statistical strategies ignore some key latent information contained in scRNA-seq data with high sparsity and heterogeneity.
View Article and Find Full Text PDFSingle-cell RNA sequencing (scRNA-seq) detects whole transcriptome signals for large amounts of individual cells and is powerful for determining cell-to-cell differences and investigating the functional characteristics of various cell types. scRNA-seq datasets are usually sparse and highly noisy. Many steps in the scRNA-seq analysis workflow, including reasonable gene selection, cell clustering and annotation, as well as discovering the underlying biological mechanisms from such datasets, are difficult.
View Article and Find Full Text PDFTumor-infiltrating T cells are essential players in tumor immunotherapy. Great progress has been achieved in the investigation of T cell heterogeneity. However, little is well known about the shared characteristics of tumor-infiltrating T cells across cancers.
View Article and Find Full Text PDFThe mortality rate from cervical cancer (CESC), a malignant tumor that affects women, has increased significantly globally in recent years. The discovery of biomarkers points to a direction for the diagnosis of cervical cancer with the advancement of bioinformatics technology. The goal of this study was to look for potential biomarkers for the diagnosis and prognosis of CESC using the GEO and TCGA databases.
View Article and Find Full Text PDFA norm in modern medicine is to prescribe polypharmacy to treat disease. The core concern with the co-administration of drugs is that it may produce adverse drug-drug interaction (DDI), which can cause unexpected bodily injury. Therefore, it is essential to identify potential DDI.
View Article and Find Full Text PDFN6-methyladenosine (mA) is the most abundant within eukaryotic messenger RNA modification, which plays an essential regulatory role in the control of cellular functions and gene expression. However, it remains an outstanding challenge to detect mRNA mA transcriptome-wide at base resolution via experimental approaches, which are generally time-consuming and expensive. Developing computational methods is a good strategy for accurate in silico detection of mA modification sites from the large amount of RNA sequence data.
View Article and Find Full Text PDFNucleic Acids Res
December 2022
Recent advances in spatial transcriptomics (ST) have brought unprecedented opportunities to understand tissue organization and function in spatial context. However, it is still challenging to precisely dissect spatial domains with similar gene expression and histology in situ. Here, we present DeepST, an accurate and universal deep learning framework to identify spatial domains, which performs better than the existing state-of-the-art methods on benchmarking datasets of the human dorsolateral prefrontal cortex.
View Article and Find Full Text PDFN6,2'-O-dimethyladenosine (mAm) is a post-transcriptional modification that may be associated with regulatory roles in the control of cellular functions. Therefore, it is crucial to accurately identify transcriptome-wide mAm sites to understand underlying mAm-dependent mRNA regulation mechanisms and biological functions. Here, we used three sequence-based feature-encoding schemes, including one-hot, nucleotide chemical property (NCP), and nucleotide density (ND), to represent RNA sequence samples.
View Article and Find Full Text PDFDNA methylation is an important epigenetics, which occurs in the early stages of tumor formation. And it also is of great significance to find the relationship between DNA methylation and cancer. This paper proposes a novel model, iCancer-Pred, to identify cancer and classify its types further.
View Article and Find Full Text PDFThe rapid development of single-cel+l RNA sequencing (scRNA-seq) technology provides unprecedented opportunities for exploring biological phenomena at the single-cell level. The discovery of cell types is one of the major applications for researchers to explore the heterogeneity of cells. Some computational methods have been proposed to solve the problem of scRNA-seq data clustering.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), is a major threat to public health worldwide. Previous studies have shown that the spike protein of SARS-CoV-2 determines viral infectivity and major antigenicity. However, the spike protein has been undergoing various mutations, which bring a great challenge to the prevention and treatment of COVID-19.
View Article and Find Full Text PDFMessenger RNA (mRNA) vaccines have shown great potential for anti-tumor therapy due to the advantages in safety, efficacy and industrial production. However, it remains a challenge to identify suitable cancer neoantigens that can be targeted for mRNA vaccines. Abnormal alternative splicing occurs in a variety of tumors, which may result in the translation of abnormal transcripts into tumor-specific proteins.
View Article and Find Full Text PDFImmune system plays important roles in the pathogenesis of Parkinson's disease (PD). However, the role of B cells in this complex disease are still not fully understood. B cells produce antibodies but can also regulate immune responses.
View Article and Find Full Text PDFAccurate prediction of immunogenic peptide recognized by T cell receptor (TCR) can greatly benefit vaccine development and cancer immunotherapy. However, identifying immunogenic peptides accurately is still a huge challenge. Most of the antigen peptides predicted in silico fail to elicit immune responses in vivo without considering TCR as a key factor.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge with Glu329 of hACE2, which resulted in greater electrostatic complementarity, and created a weak salt bridge with Asp442 of RBD.
View Article and Find Full Text PDFGreat progress has been made in the investigation on mutation and expression of splicing factor. However, little is known on the role of alternative splicing of splicing factors across cancers. Here, we reported a pan-cancer analysis of alternative splicing of splicing factors spanning 6904 patients across 16 cancer types, and identified 167 splicing factors with implications regulating cancer-specific splicing patterns through alternative splicing.
View Article and Find Full Text PDFGiven the chronic inflammatory nature of Parkinson's disease (PD), T cell immunity may be important for disease onset. Here, we performed single-cell transcriptome and TCR sequencing, and conducted integrative analyses to decode composition, function and lineage relationship of T cells in the blood and cerebrospinal fluid of PD. Combined expression and TCR-based lineage tracking, we discovered a large population of CD8 T cells showing continuous progression from central memory to terminal effector T cells in PD patients.
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