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Unraveling the HGF/MET axis in Mallory-Denk body pathogenesis associated with liver fibrosis through single-cell transcriptomics
Mallory-Denk bodies (MDBs) are protein aggregates commonly observed in chronic liver diseases, including liver fibrosis. However, the intrahepatic crosstalk driving MDB pathogenesis and fibrosis progression remains poorly understood. Using single-nucleus RNA sequencing (snRNA-seq), we identified …
Read PDFDefining neurovascular ecosystem states with single-cell multi-omics and machine learning: insights into cerebrovascular remodeling in the tumor context
<h4>Objective</h4>To define neurovascular ecosystem states within the tumor microenvironment and elucidate the regulatory basis of cerebrovascular remodeling through single-cell multi-omics and interpretable machine learning.<h4>Methods</h4>An orthotopic murine brain tumor model was established. Single-cell RNA sequencing (scRNA-seq), …
Read PDFRecent Advances in Single-Cell Analysis of Atherosclerotic Plaque Biology
Atherosclerosis, the leading cause of coronary artery disease, stroke, and peripheral arterial disease, is now recognized as a lipid-driven disease complicated by an immune response that plays a major role in its pathogenesis. The response-to-injury …
Read PDFDetailed single-cell mapping of the transcriptional response to a virus infection driven by copy-back viral genomes
The antiviral response to several clinically significant viruses, including respiratory syncytial virus and parainfluenza virus, is driven by copy-back viral genomes (cbVGs) generated during virus replication. However, the broader impact of cbVGs on the functional …
Read PDFStudy on the Potential Molecular Mechanism of Keloid Disease Associated With Single Cell Combined Mendelian Randomization
<h4>Background</h4>Keloids are pathological scars with incompletely understood pathogenesis. This study aims to identify the key genes and regulatory networks potentially involved in keloid formation by integrating single-cell transcriptomics (scRNA-seq), protein quantitative trait loci (pQTL), Mendelian …
Read PDFMultimodal integration of neuroimaging, transcriptomics and single-cell analysis reveals molecular correlates linking osteoporosis to brain abnormalities
<h4>Background</h4>Osteoporosis (OP) and cognitive decline are highly prevalent comorbidities; however, the molecular mechanisms linking them remain unclear. We adopted a multimodal integrative strategy combining neuroimaging, transcriptomics, single-cell analysis, and in vivo validation to elucidate potential …
Read PDFSingle-Cell Transcriptomic Analysis of Chemotherapy-Induced Changes in Osteosarcoma With a Pyroptosis-Related Gene-Based Prognostic Model
Osteosarcoma, the most common primary malignant bone tumour, presents significant treatment challenges due to its complex tumour microenvironment and the development of chemoresistance. This study employs single-cell transcriptomics to investigate chemotherapy-induced changes in osteosarcoma at …
Read PDFSingle-cell profiling reveals epithelial and immune responses in BK polyomavirus-infected human kidney biopsies
INTRODUCTIONBK polyomavirus (BKV) infection is associated with injury and subsequent graft loss due to the extent of injury or rejection. However, the molecular mechanisms driving injury and subsequent adverse outcomes remain poorly understood.METHODSIn a cross-sectional …
Read PDFHuman neuronal differentiation under Aβ exposure: a single-cell transcriptomic and epigenomic dataset
Human induced pluripotent stem cell-derived neural progenitor cells (NPCs) provide a controlled in-vitro model for studying early stages of neuronal differentiation. Here, we present a multimodal single-cell dataset generated from NPCs differentiated over four time …
Read PDFscMILD: Single-cell multiple instance learning for sample classification and associated subpopulation discovery
Linking cellular states to clinical phenotypes is a major challenge in single-cell analysis. Here, we present single-cell multiple instance learning for sample classification and associated subpopulation discovery (scMILD), a weakly supervised multiple instance learning framework …
Read PDFSingle-cell landscape of immune cells in multiple autoimmune diseases
Autoimmune pathologies arise from dysregulated immune activation, yet conserved molecular programs across autoimmune contexts remain incompletely characterized. Here, we analyzed integrative single-cell RNA sequencing data of over 1.3 million cells from 239 samples spanning six …
Read PDFSingle-cell RNA-seq data normalization: A benchmarking study
This study examines the noise and biases introduced by technical factors in single-cell RNA sequencing (scRNA-seq) data, presenting a thorough benchmarking analysis of six widely utilized normalization methods. The evaluation of these methods is conducted …
Read PDFMolecular insights into CRIP1 as an immunometabolic regulator revealed by CRIP1 knockout and single-cell transcriptomics
Cysteine-rich intestinal protein 1 (CRIP1) was first identified as a metabolism-related gene nearly four decades ago, yet its precise biological function remains poorly defined. More recently, CRIP1 has been implicated in several cancers, including hepatocellular …
Read PDFSingle-cell-based identification of drug synergy with immunotherapy via tumor microenvironment remodeling
<h4>Background</h4>Identifying effective therapeutic drugs in the intricate tumor microenvironment (TME) is challenging, further complicated by the lack of a systematic framework for analyzing TME perturbations in response to therapeutic interventions.<h4>Methods</h4>To address this, we established the …
Read PDFSingle-cell transcriptomics of bronchoalveolar lavage reveals divergent macrophage subpopulations and trajectories in interstitial lung disease
<h4>Rationale</h4>Interstitial lung diseases (ILDs) encompass a diverse range of fibrotic conditions and contribute to significant respiratory morbidity and mortality. Assessment of the cellular composition of bronchoalveolar lavage (BAL) fluid is an important diagnostic test in …
Read PDFSingle-cell phenotype-associated subpopulation identification via transfer foundation model and statistical ensemble learning
<h4>Background</h4>Single-cell RNA sequencing (scRNA-seq) enables the characterization of cell types, states, and lineages within heterogeneous tissues, thereby providing unprecedented opportunities to dissect cellular heterogeneity. However, single-cell data alone cannot directly establish cell-phenotype relationships, which pose …
Read PDFA differential single-cell transcriptome atlas of left-sided and right-sided colorectal cancer
Left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) show marked differences in prognosis and therapeutic response, yet the underlying molecular mechanisms remain poorly understood. We hypothesize that these clinical differences reflect distinct cell-type-specific transcriptional …
Read PDFSingle-cell insights into cisplatin resistance mechanisms in bladder cancer tumor microenvironment
This study integrates single-cell RNA sequencing with in vitro experimental validation to elucidate the molecular mechanisms underlying cisplatin resistance in bladder cancer (BC) and to characterize cellular heterogeneity within the tumor microenvironment. By analyzing integrated …
Read PDFsingIST: An integrative method for comparative single-cell transcriptomics between disease models and humans
<h4>Motivation</h4>Disease models are fundamental tools in drug discovery and early-stage drug development, but they only approximate human disease, and selecting a suitable model is challenging. Quantitative computational methods exist to assess molecular resemblance to human …
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