Biology subjects

Xin, R.

Publications and source records attributed to Xin, R..

7 recordsLinked to original sources

bioRxiv2026

Evaluation of Alcohol, Tobacco, and HPVs Synergistic regulation of Head and Neck Squamous Cell Carcinoma Treatment Response to PD-L1 Checkpoint Inhibitor Treatment

Although immune checkpoint inhibitors targeting the programmed death-ligand 1 (PD-L1) axis have transformed the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), durable clinical responses remain limited to a minority of patients, and the determinants of treatment resistance remain incompletely understood. Human papillomavirus (HPV) infection, alcohol consumption, tobacco use, and are the three most prominent etiological risk factors for HNSCC; however, despite their well-established individual roles in disease development, the influence of their combined exposure on PD-L1 axis regulation and immunotherapy response remains largely unexplored. In this study, we analyzed multi-omic data from 498 primary HNSCC tumors in The Cancer Genome Atlas (TCGA), stratifying patients into seven subgroups reflecting all observed exposure combinations, with HPV status determined directly from RNA-sequencing reads using Pathoscope. Notably, PD-L1 (CD274) expression was significantly downregulated in the triple-exposure cohort (1.51-fold reduction, p < 0.05), along with reduced expression of the upstream regulator JAK2 (1.44-fold reduction, p < 0.05) being seen. Immune deconvolution suggested progressively greater immune infiltration with accumulating exposures, yet gene set enrichment analysis revealed concurrent downregulation of T cell activation, T cell differentiation, and NK cell-mediated immunity in the triple-exposure subgroup -- consistent with an inflamed but functionally suppressed tumor microenvironment. Preliminary integration with an independent single-cell RNA-sequencing dataset of HNSCC patients undergoing neoadjuvant PD-1/CTLA-4 blockade further suggested enrichment of granulocyte and regulatory T cell populations among non-responding patients. Survival differences between cohorts were also observed, likely reflecting biological heterogeneity driven by distinct etiologies and differences in clinical presentation across exposure groups. Together, these findings provide early insights into how multi-etiological exposure burden may shape PD-L1 axis dysregulation and immune microenvironment remodeling in HNSCC, with potential implications for patient stratification in checkpoint inhibitor therapy.

cancer biology↗

bioRxiv2026

DOC Release and Physiological Response of Zostera marina Under Light and Nutrient Gradients

The seagrass bed, known as an important blue carbon ecosystem, not only has robust carbon sequestration capacity, but also releases the fixed organic carbon into the water column in the form of dissolved organic carbon (DOC). Zostera marina is the main constructive species of the seagrass meadows of northern China, but the regulatory mechanism of its DOC release in response to environmental changes still remains unclear. Adult Z. marina was used as the experimental material in this research to investigate the effects of light intensity and nutrient concentration on its DOC release, and to observe its physiological responses. By using a total organic carbon (TOC) analyzer, dissolved oxygen monitoring, transmission electron microscopy (TEM), and transcriptome analysis, we explored how light and nutrients affect DOC release and the underlying physiological mechanisms in Z. marina. The results showed that both elevated light intensity and short-term nutrient enrichment promoted organic carbon release from Z. marina to the environment. Increased light enhanced the net primary productivity (NPP) of Z. marina, while the magnitude of DOC release increased more than NPP itself. Nutrient enrichment reduced NPP while raising the proportion of DOC released by Z. marina. Transcriptome analysis showed that nutrient enrichment significantly affected pathways, including flavonoid biosynthesis and fatty acid degradation. This study demonstrated that changes in light and nutrients can significantly influence DOC release and carbon allocation patterns in Z. marina, providing a theoretical basis for blue carbon accounting and ecological restoration evaluation in seagrass beds.

plant biology↗

bioRxiv2026

Scalable genotyping in fixed transcriptomes resolves clonal heterogeneity via single-cell sequencing

Despite the promise of single-cell transcriptomics for understanding cell states in heterogeneous populations, widely used platforms have limited ability to link transcriptional states to somatic mutations within the same cells. Here, we introduce Genotyping in Fixed Transcriptomes (GIFT) for the simultaneous detection of large numbers of targeted genetic variants with whole transcriptome profiles in single cells. The core innovation of GIFT is a rationally designed gapfilling reaction between adjacent single-stranded DNA (ssDNA) probes that barcodes native transcript sequence to enable highly-specific targeted mutation detection. GIFT achieves greater than 99% genotyping accuracy and flexible capture of hundreds of mutations per cell, including in formalin-fixed, paraffin-embedded (FFPE) tissue, enabling clonal lineage tracing in heterogeneous settings. We demonstrate the unique scalability of GIFT by profiling more than 700,000 cells from 35 donors with myeloproliferative neoplasms (MPN), revealing mutation-dependent hematopoietic responses to systemic inflammation associated with the characteristic JAK2V617 mutation, including an allelic dose gradient of interferon-associated transcriptional programs and priming of hematopoietic stem cells that develop into divergent disease states. The technical advantages of GIFT enable direct resolution of genotype-to-phenotype relationships via clonal tracing with comprehensive cell-state measurements at single-cell resolution.

genomics↗

bioRxiv2023

Evolutionary and Developmental Specialization of Foveal Cell Types in the Marmoset

In primates, high-acuity vision is mediated by the fovea, a small specialized central region of the retina. The fovea, unique to the anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, the extent of cellular similarity across anthropoid foveas and the molecular underpinnings of foveal maturation remain unclear. Here, we used high throughput single cell RNA sequencing to profile retinal cells of the common marmoset (Callithrix jacchus), an early divergent in anthropoid evolution from humans, apes, and macaques. We generated atlases of the marmoset fovea and peripheral retina for both neonates and adults. Our comparative analysis revealed that marmosets share almost all its foveal types with both humans and macaques, highlighting a conserved cellular structure among primate foveas. Furthermore, by tracing the developmental trajectory of cell types in the foveal and peripheral retina, we found distinct maturation paths for each. In-depth analysis of gene expression differences demonstrated that cone photoreceptors and Muller glia, among others, show the greatest molecular divergence between these two regions. Utilizing single-cell ATAC-seq and gene-regulatory network inference, we uncovered distinct transcriptional regulations differentiating foveal cones from their peripheral counterparts. Further analysis of predicted ligand-receptor interactions suggested a potential role for Muller glia in supporting the maturation of foveal cones. Together, these results provide valuable insights into foveal development, structure, and evolution. Significance statementThe sharpness of our eyesight hinges on a tiny retinal region known as the fovea. The fovea is pivotal for primate vision and is susceptible to diseases like age-related macular degeneration. We studied the fovea in the marmoset-a primate with ancient evolutionary ties. Our data illustrated the cellular and molecular composition of its fovea across different developmental ages. Our findings highlighted a profound cellular consistency among marmosets, humans, and macaques, emphasizing the value of marmosets in visual research and the study of visual diseases.

neuroscience↗

bioRxiv2023

Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage

Deep mutational scanning (DMS) enables functional insight into protein mutations with multiplexed measurements of thousands of genetic variants in a protein simultaneously. The small sample size of DMS renders classical statistical methods ineffective, for example, p-values cannot be correctly calibrated when treating variants independently. We propose Rosace, a Bayesian framework for analyzing growth-based deep mutational scanning data. Rosace leverages amino acid position information to increase power and control the false discovery rate by sharing information across parameters via shrinkage. To benchmark Rosace against existing methods, we developed Rosette, a simulation framework that simulates the distributional properties of DMS. Further, we show that Rosace is robust to the violation of model assumptions and is more powerful than existing tools under Rosette simulation and real data.

bioinformatics↗

bioRxiv2022

SWAP1-SFPS-RRC1 splicing factor complex modulates pre-mRNA splicing to promote photomorphogenesis in Arabidopsis

Light signals perceived by a group of photoreceptors have profound effects on the physiology, growth, and development of plants. The red/far-red light absorbing phytochromes modulate these aspects by intricately regulating gene expression at multiple levels. Previously, we reported that two splicing factors SFPS (SPLICING FACTOR FOR PHYTOCHROME SIGNALING) and RRC1 (REDUCED RED LIGHT RESPONSES IN CRY1CRY2 BACKGROUND 1), interact with photoactivated phyB to regulate light-mediated pre-mRNA alternative splicing (AS). Here, we report the identification and functional characterization of an RNA binding splicing factor, SWAP1 (SUPPRESSOR-OF-WHITE-APRICOT/SURP RNA-BINDING DOMAIN-CONTAINING PROTEIN1). Loss-of-function swap1-1 mutant is hyposensitive to red light and exhibits a day light-independent early flowering phenotype. SWAP1 physically interacts with both SFPS and RRC1 in a light-independent manner and forms a ternary complex. In addition, SWAP1 also physically interacts with photoactivated phyB and colocalizes with nuclear phyB photobodies. Deep RNA-seq analyses show that SWAP1 regulates the gene expression and pre-mRNA alternative splicing of a large number of genes including those involved in plant responses to light signaling. A comparison with SFPS- and RRC1-regulated events shows that all three splicing factors coordinately regulate the alternative splicing of a subset of genes. Collectively, our study uncovered the function of a new splicing factor, which interacts with photoactivated phyB, in modulating light-regulated development in plants. SIGNIFICANCERegulation of transcription and pre-mRNA alternative splicing is essential for the transcript diversity and modulation of light signaling in plants. Although several transcription factors involved in light signaling have been discovered and characterized in-depth, only a few splicing factors have been shown to be involved in the regulation of light signaling pathways. In this study, we describe the identification and characterization of a new splicing factor SWAP1, which interact with two previously characterized splicing factors, SFPS and RRC1, forming a ternary complex. We show that, like SFPS and RRC1, SWAP1 also interacts with photoactivated phyB, and consistently, swap1 seedlings are hyposensitive to red light. SWAP1 modulates alternative splicing of a large number of genes and a subset of these genes are coordinately regulated by SFPS, RRC1 and SWAP1. These results highlight the importance of not only the transcription factors but also the phyB-interacting splicing factors in light-regulated plant development.

plant biology↗

bioRxiv2018

scCapsNet: a deep learning classifier with the capability of interpretable feature extraction, applicable for single cell RNA data analysis

Recently deep learning methods have been applied to process biological data and greatly pushed the development of the biological research forward. However, the interpretability of the deep learning methods still needs to improve. Here for the first time, we present scCapsNet, a totally interpretable deep learning model adapted from CapsNet. The scCapsNet model retains the capsule parts of CapsNet but replaces the part of convolutional neural networks with several parallel fully connected neural networks. We apply scCapsNet to scRNA-seq data. The results show that scCapsNet performs well as a classifier and also that the parallel fully connected neural networks function like feature extractors as we supposed. The scCapsNet model provides contribution of each extracted feature to the cell type recognition. Evidences show that some extracted features are nearly orthogonal to each other. After training, through analysis of the internal weights of each neural network connected inputs and primary capsule, and with the information about the contribution of each extracted feature to the cell type recognition, the scCapsNet model could relate gene sets from inputs to cell types. The specific gene set is responsible for the identification of its corresponding cell types but does not affect the recognition of other cell types by the model. Many well-studied cell type markers are in the gene set with corresponding cell type. The internal weights of neural network for those well-studied cell type markers are different for different primary capsules. The internal weights of neural network connected to a primary capsule could be viewed as an embedding for genes, convert genes to real value low dimensional vectors. Furthermore, we mix the RNA expression data of two cells with different cell types and then use the scCapsNet model trained with non-mixed data to predict the cell types in the mixed data. Our scCapsNet model could predict cell types in a cell mixture with high accuracy.

bioinformatics↗