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Single-cell chromatin accessibility profiles are extremely sparse but reflect continuous developmental trajectories. Most existing methods for dimensionality reduction and trajectory analysis optimize reconstruction error or cluster separation, without encoding temporal continuity in the model or …
Read PDFThe protein tyrosine phosphatase SHP2, encoded by <i>PTPN11</i>, is an important regulator of Ras/mitogen-activated protein kinase signaling that acts downstream of receptor tyrosine kinases and other transmembrane receptors. Germline <i>PTPN11</i> mutations cause developmental disorders such …
Read PDF<h4>Background</h4>Endometriosis (EMs) affects approximately 10% of reproductive-age women worldwide, yet its pathogenesis remains incompletely understood. Abnormal cell differentiation and somatic mutations in the ectopic endometrial microenvironment play critical roles in disease progression and treatment response …
Read PDFSingle-cell optimization objective and trade-off inference (SCOOTI) is a computational framework that integrates bulk and single-cell omics data with genome-scale metabolic modeling to infer metabolic objectives and trade-offs in biological systems. Here, we present a …
Read PDFInfiltrating gliomas are the most common primary malignant brain tumor and remain universally fatal. Over the past decade, advances in single-cell technologies, including single-cell RNA sequencing, have significantly advanced our understanding of malignant cells in …
Read PDFDuring vertebrate embryogenesis, axial tendons develop from the paraxial mesoderm and differentiate through specific developmental stages to reach the syndetome stage. While the main roles of signaling pathways in the earlier stages of differentiation have …
Read PDF<h4>Background</h4>The immunosuppressive tumor microenvironment in colorectal cancer is a key factor in its progression and treatment resistance, yet the coordinated mechanisms of its cellular composition and signaling networks are not fully understood. This study aims …
Read PDFContext-specific expression quantitative trait loci (eQTLs) mediate genetic risk for complex diseases, but current methods limit their characterization and interpretation. We introduce FastGxC, a method for efficiently mapping context-specific eQTLs by leveraging correlation structure in …
Read PDFAdvances in single-cell sequencing and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technologies have enabled detailed case-control comparisons and experimental perturbations at single-cell resolution. However, uncovering causal relationships in observational genomic data remains challenging due …
Read PDFClonal fitness and plasticity drive tumor heterogeneity contributing to disease progression and treatment resistance. Here, we provide a protocol to track the clonal outputs from uniquely marked cells. We describe steps for constructing and validating …
Read PDFSingle-cell RNA sequencing technologies profile the transcriptome of individual cells but lack the spatial context necessary for dissecting cellular interactions like cell-cell communications. On the other hand, most current spatial transcriptomic technologies lack cellular resolution, …
Read PDFBrain metastasis remains a significant cause of morbidity and mortality for cancer patients with limited treatment options. Single-cell RNA-seq has greatly expanded our ability to study cancer and metastasis, particularly in our assessment of tumor …
Read PDFThe zebrafish lateral line system is a sensory network made up of neuromasts, which contain hair cells to detect water flow. Neuromasts signal via sensory afferent neurons and their activity is modulated by efferent neurons. …
Read PDFThe molecular programs governing early female gonadal development in livestock remain incompletely characterized. Here, we generated a single-cell transcriptomic atlas of bovine fetal ovaries spanning sex determination to early folliculogenesis and performed an integrated cross-species …
Read PDFSingle-cell RNA sequencing (scRNA-seq) data are inherently high-dimensional, and most analysis tools reduce this complexity by projecting the data into a low-dimensional latent space before performing downstream analyses. However, the resulting representations are often entangled, …
Read PDFImmune checkpoint blockade (ICB) induces durable responses in a subset of breast cancer patients, yet many show limited benefit from anti-PD-1/PD-L1 therapy. Understanding differences in the tumor microenvironment (TME) and tumor-intrinsic immune evasion between responders …
Read PDFOBJECTIVE: High heterogeneity and poor therapeutic response are major challenges in hepatocellular carcinoma (HCC). This study aimed to identify core hepatocyte subsets and key genes driving HCC progression via a multi-omics approach to inform precise …
Read PDFThe evolution of distinct lung architectures in birds (tubular air capillaries) and mammals (alveoli) represents a classic example of convergent evolution, yet their cellular differences remain poorly characterized. We present the comparative single-cell atlas of …
Read PDFHepatocellular carcinoma (HCC) exhibits pronounced cellular heterogeneity and dynamic state transitions during tumour progression, yet the emergence of tumour cell states along fate trajectories and their transcriptional regulation remain unclear. Here, we established an integrated …
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