Dimension reduction, cell clustering, and cell-cell communication inference for single-cell transcriptomics with DcjComm.

Advances 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.

Neoadjuvant immunochemotherapy improves clinical outcomes of patients with esophageal cancer by mediating anti-tumor immunity of CD8+ T (Tc1) and CD16+ NK cells.

Background: Esophageal cancer (ESCA) is one of the most common tumors in the world, and treatment using neoadjuvant therapy (NT) based on radiotherapy and/or chemotherapy has still unsatisfactory results. Neoadjuvant immunochemotherapy (NICT) has also become an effective treatment strategy nowadays. However, its impact on the tumor microenvironment (TME) and regulatory mechanisms on T cells and NK cells needs to be further elucidated.

Anti-CTLA-4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5-Neutrophil Infiltration.

The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis.

Functional requirement of alternative splicing in epithelial-mesenchymal transition of pancreatic circulating tumor.

Circulating 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.

CancerProteome: a resource to functionally decipher the proteome landscape in cancer.

Advancements in mass spectrometry (MS)-based proteomics have greatly facilitated the large-scale quantification of proteins and microproteins, thereby revealing altered signalling pathways across many different cancer types. However, specialized and comprehensive resources are lacking for cancer proteomics. Here, we describe CancerProteome (http://bio-bigdata.

DeepCCI: a deep learning framework for identifying cell-cell interactions from single-cell RNA sequencing data.

Motivation: 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.

Identification of shared characteristics in tumor-infiltrating T cells across 15 cancers.

Tumor-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.

Spatial transcriptome analysis of long non-coding RNAs reveals tissue specificity and functional roles in cancer.

Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states.

DeepST: identifying spatial domains in spatial transcriptomics by deep learning.

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.

Network analysis between neuron dysfunction and neuroimmune response based on neural single-cell transcriptome of COVID-19 patients.

Despite global vaccination efforts, COVID-19 breakthrough infections caused by variant virus continue to occur frequently, long-term sequelae of COVID-19 infection like neuronal dysfunction emerge as a noteworthy issue. Neuroimmune disorder induced by Inflammatory factor storm was considered as a possible reason, however, little was known about the functional factors affecting neuroimmune response to this virus. Here, using medial prefrontal cortex single cell data of COVID-19 patients, expression pattern analysis indicated that some immune-related pathway genes expressed specifically, including genes associated with T cell receptor, TNF signaling in microglia and Cytokine-cytokine receptor interaction and HIF-1 signaling pathway genes in astrocytes.

MutCov: A pipeline for evaluating the effect of mutations in spike protein on infectivity and antigenicity of SARS-CoV-2.

Severe 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.

Krüppel-like Transcription Factor 7 Is a Causal Gene in Autism Development.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disease. To date, more than 1000 genes have been shown to be associated with ASD, and only a few of these genes account for more than 1% of autism cases. Klf7 is an important transcription factor of cell proliferation and differentiation in the nervous system, but whether klf7 is involved in autism is unclear.

Identification of alternative splicing-derived cancer neoantigens for mRNA vaccine development.

Messenger 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.

Global Characterization of Peripheral B Cells in Parkinson's Disease by Single-Cell RNA and BCR Sequencing.

Immune 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.

DLpTCR: an ensemble deep learning framework for predicting immunogenic peptide recognized by T cell receptor.

Accurate 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.

N439K Variant in Spike Protein Alter the Infection Efficiency and Antigenicity of SARS-CoV-2 Based on Molecular Dynamics Simulation.

Severe 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.

A pan-cancer analysis of alternative splicing of splicing factors in 6904 patients.

Great 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.

Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson's disease.

Given 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.

Comprehensive analysis of partial methylation domains in colorectal cancer based on single-cell methylation profiles.

Epigenetic aberrations have played a significant role in affecting the pathophysiological state of colorectal cancer, and global DNA hypomethylation mainly occurs in partial methylation domains (PMDs). However, the distribution of PMDs in individual cells and the heterogeneity between cells are still unclear. In this study, the DNA methylation profiles of colorectal cancer detected by WGBS and scBS-seq were used to depict PMDs in individual cells for the first time.

Alternative splicing associated with cancer stemness in kidney renal clear cell carcinoma.

Backgroud: Cancer stemness is associated with metastases in kidney renal clear cell carcinoma (KIRC) and negatively correlates with immune infiltrates. Recent stemness evaluation methods based on the absolute expression have been proposed to reveal the relationship between stemness and cancer. However, we found that existing methods do not perform well in assessing the stemness of KIRC patients, and they overlooked the impact of alternative splicing.

Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing.

The world is facing a pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adaptive immune responses are essential for SARS-CoV-2 virus clearance. Although a large body of studies have been conducted to investigate the immune mechanism in COVID-19 patients, we still lack a comprehensive understanding of the BCR repertoire in patients.

Comprehensive analysis of TCR repertoire in COVID-19 using single cell sequencing.

T-cell receptor (TCR) is crucial in T cell-mediated virus clearance. To date, TCR bias has been observed in various diseases. However, studies on the TCR repertoire of COVID-19 patients are lacking.