Biology subjects

Ren, Y.

Publications and source records attributed to Ren, Y..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

Gut meta-virome reveals potential zoonotic pathogens and environmental RNA viruses carried by non-human primates

The majority of human infectious diseases originate from mammals and are inherently zoonotic. Non-human primates (NHPs) are not only carriers of many zoonotic pathogens, but also the best intermediary for virus shift from harmless to harmful due to their similar phylogenetic relationship with humans. Knowledge of NHP viral composition and its underlying information can therefore provide an assessment of the risk of cross-species transmission and spillover of zoonotic diseases. However, studies that have successfully eliminated the effects of different natural habitat environments on viral carriage have been limited, making it difficult to identify which zoonotic viruses and potentially species-barrier-crossing viruses are carried by widely distributed NHP hosts. Here, we analyze viruses excreted in feces from NHP hosts and reveal the presence of possible zoonotic pathogens. Most of the viruses found come from plants that are eaten by them. Analysis of the evolutionary relationships of potential pathogens suggests that other clinical isolates are genetically correlated to HIV, PBV, and EV we identified. This study provides foundational data for surveillance of NHP enteroviruses that could help to be challenging to track potential human viruses carried by NHP in the absence of clinical surveillance. ImportanceAs a result of internationalization and other factors, many viruses have broken through the limits of geographical units and spread into human society, causing many emerging and re-emerging infectious disease hazards. However, the virus spreads and is by no means infectious to humans overnight. There is a phenomenon of host shift, in which the virus does not necessarily cause disease in an intermediate host, but causes significant damage when transmitted to humans. We focus on captive non-human primates, close relatives of humans in cities, because the phenomenon of host shifts is related to both biological similarity and geographical proximity of the host. Primates may carry zoonotic viruses and viruses that are currently incapable of infecting humans but have evolved with pathogenic potential. In summary, comprehensive viral surveillance and screening of captive nonhuman primates is necessary.

ecology↗

bioRxiv2024

Single CAR-Dual target: Intracranial Delivery of Anti-PD-L1 CAR T Cells Effectively Eradicates Glioma and Immunosuppressive Cells in the Tumor Microenvironment.

With the goal to overcome the limited treatment options and poor prognosis of glioblastoma (GBM), we have developed a PD-L1-targeting CAR T cell therapy, MC9999. In vitro experiments with MC9999 CAR T cells derived from GBM patients exhibited potent, antigen-specific cytotoxicity against autologous tumor cells and immunosuppressive cells within the tumor microenvironment (TME). In an orthotopic GBM model using patient-derived brain tumor-initiating cells, the intracranial delivery of MC9999 CAR T cells eradicated established tumors and improved survival. Single-cell RNA sequencing indicated that MC9999 CAR T cells activate interferon pathways, leading to GBM cell apoptosis. Multi-immunohistochemistry confirmed localized PD-L1 expression on tumor cells and TME-residing macrophages, but not in neurons or glia in patient tissue. The local delivery of MC9999 CAR T cells may be a safe, effective approach for simultaneously targeting PD-L1-positive GBM and its immunosuppressive TME and a strategy to overcome immune evasion and enhance the therapeutic potency of CAR T cell therapy against GBM.

cancer biology↗

bioRxiv2024

Screening of potential biomarkers using activity-based protein profiling in a rat model of chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting cancer patients, often resulting from the use of neurotoxic agents, such as paclitaxel. This study aimed to establish a rat model of CIPN through systemic administration of paclitaxel and to identify potential biomarkers using activity-based protein profiling (ABPP) with a desthiobiotin iodoacetamide (DBIA) probe. Male Sprague-Dawley rats received paclitaxel injections at a dosage of 2 mg/kg on Days 0, 2, 4, and 6. Behavioral assessments revealed significant mechanical and thermal pain hypersensitivity in paclitaxel-treated rats compared to control groups. ABPP analysis identified a total of 2,445 proteins and 6,765 peptides, resulting in the identification of 7 candidate proteins as potential biomarkers for CIPN. Notably, 5 proteins were significantly upregulated, while 2 protein including Q63425 (Prx) demonstrated downregulation in response to paclitaxel. These findings suggest that alterations in candidate protein levels may compromise alterations in the spinal cord in the context of CIPN. This study underscores the utility of ABPP in elucidating the proteomic changes associated with CIPN and highlights the potential of identified biomarkers like Prx for enhancing our understanding of chemotherapy-induced neuropathic pain mechanisms.

molecular biology↗

bioRxiv2024

A Genomic Language Model for Chimera Artifact Detection in Nanopore Direct RNA Sequencing

Chimera artifacts in nanopore direct RNA sequencing (dRNA-seq) can significantly distort transcriptome analyses, yet their detection and removal remain challenging due to limitations in existing basecalling models. We present Deep-Chopper, a genomic language model that precisely identifies and removes adapter sequences from base-called dRNA-seq long reads at single-base resolution, operating independently of raw signal or alignment information to effectively eliminate chimeric read artifacts. By removing these artifacts, DeepChopper substantially improves the accuracy of critical downstream analyses, such as transcript annotation and gene fusion detection, thereby enhancing the reliability and utility of nanopore dRNA-seq for transcriptomics research.

genomics↗

bioRxiv2024

The EZH2 inhibitor tazemetostat mitigates HIV immune evasion, reduces reservoir formation, and promotes durable CD8+ T-cell revitalization

Persistent HIV reservoirs in CD4 T-cells pose a barrier to curing HIV infection. We identified overexpression of enhancer of zeste homolog 2 (EZH2) in HIV-infected CD4 T- cells that survive cytotoxic T lymphocyte (CTL) exposure, suggesting a mechanism of CTL resistance. Inhibition of EZH2 with the FDA-approved drug tazemetostat increased surface expression of major histocompatibility complex class I (MHC-I) on CD4 T-cells, counterbalancing HIV Nef-mediated MHC-I downregulation. This improved CTL-mediated elimination of HIV-infected cells and suppressed viral replication in vitro. In a participant-derived xenograft mouse model, tazemetostat elevated MHC-I and the pro-apoptotic protein BIM in CD4 T-cells, facilitating CD8 T-cell-mediated reductions of HIV reservoir seeding. Additionally, tazemetostat promoted sustained skewing of CD8 T-cells toward less differentiated and exhausted phenotypes. Our findings reveal EZH2 overexpression as a novel mechanism of CTL resistance and support the clinical evaluation of tazemetostat to enhance clearance of HIV reservoirs and improve CD8+ T-cell function.

immunology↗

bioRxiv2024

Ligand-Receptor Interactions for Cell-Cell Communication Analysis in Rat, Chicken, Pig, and Monkey Single-Cell and Spatial Transcriptomics

Cell-cell communication is a frequently used analysis approach in single cell RNA and spatial transcriptomics, and many tools like CellPhoneDB, CellChat and stLearn have been developed. Ligand-receptor interactions are the core of cell-cell communication analysis. Since receptor-ligand and even protein-protein interactions were focus on humans and mice research, curated human and mouse receptor-ligand databases have been established, cell-cell interactions for these two species single-cell RNA sequencing data can be directly analyzed. However, for rats, chickens, pigs, monkeys, and other species, cell-cell interaction analysis is often implemented through orthologous gene mapping, due to the lack of curated ligand-receptor interaction databases for these species. We collected cell-cell interaction data mainly from KEGG for rats, chickens, pigs, and monkeys, and extended the data from Reactome and IntAct. Then, by using CellChatV2 with our collected rat ligand-receptor interactions and CellChatV2s own mouse data, respectively, we analyzed 10x Genomics rat public scRNA data, and found that 70 significantly ligand-receptor interactions from the mouse analysis result were also significantly in rats. We also obtained some chicken, pig, and monkey scRNA data from published literature, and analyzed cell-cell interactions using our collected ligand-receptor interactions for these species, and it was proved that our data is reliable and useful. Lastly, we have transformed the ligand-receptor interactions for rat, chicken, pig, and monkey species into the CellChatDB format, which enables swift and straightforward analysis of cell-cell communication in single-cell and spatial data of these four species. All the ligand-receptor interaction datasets for rats, chickens, pigs, and monkeys, as well as the program codes, are available at https://github.com/qingchen36/ligand-receptor. Using our program, one can rapidly obtain receptor-ligand interaction data for other species.

bioinformatics↗

bioRxiv2024

Novel regulator Fpr2 controls immune homeostasis via CCL4-dependent neutrophils

Polymorphonuclear leukocytes (PMNs) in Fpr2-deficient mice have significantly impaired bactericidal activity, yet the precise mechanism remains elusive. Our research unveiled the cellular heterogeneity of peripheral blood PMNs through single-cell RNA-sequencing (scRNA-seq) and identified two new neutrophil clusters related to bacterial infection, including a sterilization cluster named Neu_CSTA and a regulation cluster named Neu_CCL4. The lack of Fpr2 leads to an immune regulation imbalance of Neu_CCL4 on other clusters in uninfected conditions, resulting in persistent instability of PMNs in peripheral blood, elevated inflammatory factors, and increased NOX2 expression. Furthermore, our findings corroborate that the regulatory function of Neu_CCL4 on PMNs immune balance is closely tied to its high expression of the anti-inflammatory ligand Anxa1. Regulon analysis inferred by scRNA-seq and ChIP-seq data suggested that a specific transcription factor Elf4, could modulate the expression of Anxa1, thereby facilitating its regulatory impact on other clusters. In the infection state, there was a noted increase in intercellular interactions across different clusters, leading to a general improvement in the bactericidal activity of PMNs. In summary, our research revealed distinct functional cellular sub-populations of PMNs, discovered the potential regulatory mechanisms, and elucidated the essential roles of Fpr2 in their ability to resist infection.

immunology↗

bioRxiv2024

A brainstem circuit controls cough-like airway defensive behaviors in mice

The respiratory tract is subject to complex neural control for eupneic breathing and distinct airway defensive reflexes. Growing evidence has highlighted significant heterogeneity of airway-innervating vagal sensory neurons in mediating various respiratory functions, however, the central neuronal pathways and neural circuits involved in the airway regulation remain less understood. Combining whole-body plethysmography (WBP), audio, and video tracking to access breathing and airway defensive behaviors in conscious animals, we developed a quantitative paradigm implementing the mouse as a model to study cough-like defensive behaviors. Using TRAP2 transgenic mice and in vivo fiber photometry, we found that the neural activity in the caudal spinal trigeminal nucleus (SP5C) is strongly correlated with tussigen-evoked cough-like responses. Impairing synaptic outputs or chemogenetic inhibition of the SP5C effectively abolished these cough-like reflexes. Optogenetic stimulation of SP5C excitatory neurons or their projections to the ventral respiratory group (VRG) triggered robust cough-like behaviors without tussive stimuli. Notably, tonic elevation of SP5C excitability caused spontaneous cough-like activities chronically in mice. Together, our data provide strong evidence for a previously unrecognized brainstem circuit that controls cough-like defensive behaviors in mice.

neuroscience↗

bioRxiv2024

Coat protein of TCV suppresses RNA decay via ubiquitination and autophagy pathways to facilitate viral infection

Highlight statementThe findings highlight that TCV manipulates 26S proteasome and autophagy pathways to obstruct antiviral RNA decay defenses and ultimately enhance its ability to infect host cells. RNA decay is a pervasive process in eukaryotic cells. Viruses utilize the host cells intracellular machinery to gain access to essential molecules and subcellular structures required for infection during the pathogenesis process. The study demonstrates that turnip crinkle virus (TCV) infection enhances the expression of Arabidopsis Dcp1 (AtDcp1), which negatively regulates the accumulation of TCV RNA, indicating its involvement in antiviral defense. Nevertheless, TCV circumvents the antiviral defense based on RNA decay, as indicated by the capsid protein (CP) of TCV stabilizing the known nonsense-mediated RNA decay targeted transcripts. In vivo, CP physically interacts with AtDcp1, promoting AtDcp1 degradation via ubiquitination and autophagy pathways. This is evidenced by the observation that the degradation is inhibited by both 26S proteasome and autophagy inhibitors. Furthermore, CP elevates the polyubiquitination of Dcp1-Flag and the quantity of pre-autophagosome or autophagosome structures. These data indicate that CP suppresses RNA decay by interacting with AtDcp1 and mediating its degradation through the 26S proteasome and autophagy pathways, effectively subduing antiviral RNA decay. This study uncovers a previously unidentified virulence strategy in the ongoing conflict between plants and viruses.

pathology↗

bioRxiv2024

Nodal Modulator (NOMO) is a force-bearing transmembrane protein required for muscle differentiation

The endoplasmic reticulum (ER) relies on specialized membrane-shaping proteins to maintain a continuous network of sheets and tubules that host distinct biological processes. How this intricate structure of the ER membrane system is maintained under conditions of mechanical strain is incompletely understood. NOMO is an ER-resident transmembrane protein that contributes to ER morphology and is highly expressed in striated muscle. In this study, we identify a critical interface between distal Ig domains that enables NOMO to maintain ER morphology and buffer mechanical forces. By incorporating two independent tension sensors in the luminal domain of NOMO, we demonstrate that NOMO assemblies experience forces in the single piconewton (pN) range, with a significant contribution from the identified interface. These newly defined features are important, if not indispensable, for myogenesis, as interface mutations affecting mechanosensing fail to restore the essential role of NOMO during myogenesis in a C2C12 differentiation model. Moreover, NOMO depletion impairs nematode motility, underscoring a broader functional importance in muscle physiology.

cell biology↗

bioRxiv2024

A multidimensional Pan-cancer analysis of CDKN1A identifies CDKN1A as an Immunological and Prognostic Biomarker

CDKN1A/p21 is well recognized for its role in cell cycle regulation and genomic stability. However, its functions in the Tumor microenvironment (TME) and tumor immunity are not yet fully understood. Hereby, we explored CDKN1A expression and immunological/prognostic values via various databases and analytical methods including cBioPortal, Kaplan-Meier, UCSCXenaShiny, TIMER, Single-cell RNA sequencing (scRNA-seq) analysis, etc. In addition, we explored different approaches including CCK8, EdU, Colony formation, Drug sensitivity and Annixin-V assay to explore the influence of p21 in proliferative capacity in cancer cells. We found that CDKN1A is lowly expressed in BLCA, BRCA, COAD, KICH, LUAD, LUSC, PRAD, READ and STAD compared to normal samples, whereas it is highly expressed in CHOL, HNSC, KIRC, KIRP and THCA compared to normal cohorts. CDKN1A expression is significantly correlated with overall survival, disease-specific survival, disease-free survival and progression-free interval different cancer types. Additionally, CDKN1A is associated with CD4+ T cell, CD8+ T cell, Neutrophil, Macrophage and Myeloid dendritic cell infiltration in diverse cancer types. Functional experiments reveal that p21 overexpression leads to a significant reduction in proliferative capacity, facilitates cell apoptosis and senescence in multiple cancer cell lines. In contrast, silenced p21 facilitates cell growth and wound closure, prevent cell senescence in different cancer cell lines. In conclusion, our findings suggest that CDKN1A may serve as a valuable prognostic and immunotherapeutic marker in diverse cancer.

cancer biology↗

bioRxiv2024

A single-molecule nanopore sequencing platform

Nanopore sequencing, a third-generation sequencing technology, has revolutionized the gene sequencing industry with its advantages of long reads, fast speed, real-time sequencing and analysis, and potential in detecting base modifications. This technology allows researchers to sequence longer DNA fragments in a single read, providing more comprehensive genomic information compared to previous methods. Nanopore sequencing operates on electrical signals generated by a nanopore embedded in a membrane separating two electrolyte-filled chambers. When single-stranded DNA (ssDNA) passes through the nanopore, it creates variations in the current that correspond to different DNA bases. By analyzing these current fluctuations with machine learning algorithms, the DNA sequence can be determined. In this study, we introduced several improvements to nanopore sequencing, including nanopore local chemistry sequencing, novel motor and pore proteins, chip design, and basecalling algorithms. Our new nanopore sequencing platform, CycloneSEQ, demonstrated long-duration sequencing (107 hours) on a single chip with high yield (>50 Gb). In human genomic DNA sequencing, CycloneSEQ was able to produce long reads with N50 33.6 kb and modal identity 97.0%. Preliminary findings on human whole-genome de novo assembly, variant calling, metagenomics sequencing, and single-cell RNA sequencing have further highlighted CycloneSEQs potential across different areas of genomics.

genomics↗

bioRxiv2024

Alleviation of salt stress in strawberries by hydrogen-rich water: physiological, transcriptomic and metabolomic responses

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/605184v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1aa6488org.highwire.dtl.DTLVardef@1ae580borg.highwire.dtl.DTLVardef@11656bcorg.highwire.dtl.DTLVardef@1985c7b_HPS_FORMAT_FIGEXP M_FIG C_FIG With the continuous advancement of climate change and human activities, cultivable land is becoming increasingly susceptible to the influence of salt ions. Therefore, it is crucial to mitigate the salt stress on plants through various approaches. In this study, strawberry seedlings were selected as the experimental plants, and a comprehensive transcriptomic and metabolomic analysis was conducted to elucidate the effects of hydrogen-rich water (HRW) on strawberries under salt stress. The results indicated that HRW significantly promoted plant growth, particularly increasing root biomass by 49.50%. Additionally, HRW regulated the levels of soluble sugars, malondialdehyde (MDA), and antioxidant enzymes, enhancing the cellular uptake of potassium ions and the expulsion of sodium ions. The levels of Ca2+ and Mg2+ in organelles increased by 2.06 and 2.45-fold, respectively. Transcriptomic analysis revealed that HRW substantially altered gene expression in strawberry roots; under salt stress, HRW up-regulated beneficial biological processes. Furthermore, genes related to ion absorption and transport, antioxidant enzymes, and cell wall biosynthesis were screened. Meanwhile, key common pathways were identified in differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs) related to phenylpropane biosynthesis, alanine, aspartate, and glutamate metabolism, amino and nucleotide sugar metabolism, and galactose metabolism. A molecular mechanism for mitigating salt stress in strawberry seedlings by HRW was provided by the integrated approaches in this research, reflecting the potential applications of hydrogen gas in agriculture.

physiology↗

bioRxiv2024

Towards a new standard in genomic data privacy: a realization of owner-governance

With the rapid developments in sequencing technologies, individuals now have unprecedented access to their genomic data. However, existing data management systems or protocols are inadequate for protecting privacy, limiting individuals control over their genomic information, hindering data sharing, and posing a challenge for biomedical research. To fill the gap, an owner-governed system that fulfills owner authority, lifecycle data encryption, and verifiability at the same time is prompted. In this paper, we realized Governome, an owner-governed data management system designed to empower individuals with absolute control over their genomic data during data sharing. Governome uses a blockchain to manage all transactions and permissions, enabling data owners with dynamic permission management and to be fully informed about every data usage. It uses homomorphic encryption and zero-knowledge proofs to enable genomic data storage and computation in an encrypted and verifiable form for its whole lifecycle. Governome supports genomic analysis tasks, including individual variant query, cohort study, GWAS analysis, and forensics. Query of a variants genotype distribution among 2,504 1kGP individuals in Governome can be efficiently completed in under 18 hours on an ordinary server. Governome is an open-source project available at https://github.com/HKU-BAL/Governome.

bioinformatics↗

bioRxiv2024

Genomics-FM: Universal Foundation Model for Versatile andData-Efficient Functional Genomic Analysis

Artificial intelligence (AI) plays a crucial role in functional genomic analysis, offering great potential for comprehending biological phenomena such as heredity, development, diseases, and evolution. However, the development of AI models needs substantial labeled data, and these models are typically task-specific with limited generalizability to various applications. Here, we develop Genomics-FM, a genomic vocabulary driven foundation model that enables versatile and label-efficient functional genomic analysis. Specifically, Genomics-FM is first pretrained with ensemble genomic vocabulary on vast unlabelled data to learn comprehensive and generalizable representations and then finetuned with specific genomic vocabulary on limited labeled data to selectively activate and adapt the pretraining knowledge for specific tasks. We show that Genomics-FM significantly reduces the dependence on labeled data, and demonstrates the capability to outperform existing models across a comprehensive suite of tasks including genome annotation, epigenomic and expression profile prediction, and variant effect assessment. Remarkably, Genomics-FM even shows impressive zero-shot predictive capabilities across diverse species and tissues and exhibits noticeable adaptability to RNA-related tasks. With feasibility in data scarcity and even cross-domain biological scenarios, Genomics-FM will promote the broad application of AI and empower researchers to tackle previously insurmountable challenges, paving the way for groundbreaking research and discoveries.

bioinformatics↗

bioRxiv2024

BMAP: a comprehensive and reproducible biomedical data analysis platform

In the realm of biomedical research, efficient data analysis and processing are crucial due to the escalating volume and complexity of data generated by research teams. Managing these vast arrays of localized data presents significant challenges, necessitating precise, efficient, and reproducible analysis methodologies to ensure the integrity and reliability of scientific outcomes. Traditional management of analysis codes, computing environments, and the inherent difficulties in result traceability due to team dynamics often lead to inefficiencies and potential risks in maintaining academic integrity. Furthermore, while online storage platforms such as Dryad, GitHub, and Docker facilitate data, code, and environment management, they do not inherently guarantee the reproducibility of results, with issues like data incompleteness, forgotten parameters, or software discrepancies posing additional challenges. To address these critical gaps, we developed a BioMedical data Analysis Platform (BMAP) to offer online and localized categorized management of research assets. BMAP enhances workflow efficiency by transforming complex pipelines into user-friendly web applications, promoting consistency and standardization across team analyses. Its comprehensive web analysis module and seamless integration with data and computing resources support automated result reproducibility and visualization. According to the assessment, 1,692 omics-related figures from 101 recent articles, across 45 visualization types, were tested with BMAP, which could cover 37.8% of the types and 64.3% of the figures. BMAP also enables the sharing and enhancement of research methods through its cloud platform, allowing researchers to utilize the previously developed and validated tools, thereby reducing redundant effort and minimizing analytical discrepancies due to methodological differences.

bioinformatics↗

bioRxiv2024

BEACON: Benchmark for Comprehensive RNA Tasks and Language Models

RNA plays a pivotal role in translating genetic instructions into functional outcomes, underscoring its importance in biological processes and disease mechanisms. Despite the emergence of numerous deep learning approaches for RNA, particularly universal RNA language models, there remains a significant lack of standardized benchmarks to assess the effectiveness of these methods. In this study, we introduce the first comprehensive RNA benchmark BEACON (BEnchmArk for COmprehensive RNA Task and Language Models). First, BEACON comprises 13 distinct tasks derived from extensive previous work covering structural analysis, functional studies, and engineering applications, enabling a comprehensive assessment of the performance of methods on various RNA understanding tasks. Second, we examine a range of models, including traditional approaches like CNNs, as well as advanced RNA foundation models based on language models, offering valuable insights into the task-specific performances of these models. Third, we investigate the vital RNA language model components from the tokenizer and positional encoding aspects. Notably, our findings emphasize the superiority of single nucleotide tokenization and the effectiveness of Attention with Linear Biases (ALiBi) over traditional positional encoding methods. Based on these insights, a simple yet strong baseline called BEACON-B is proposed, which can achieve outstanding performance with limited data and computational resources. The datasets and source code of our benchmark are available at https://github.com/terry-r123/RNABenchmark.

bioinformatics↗

bioRxiv2024

CREEPING STEM1 Regulates Directional Auxin Transport for Lodging Resistance in Soybean

Soybean, a staple crop on a global scale, frequently encounters challenges due to lodging under high planting densities, which results in significant yield losses. Despite extensive research, the fundamental genetic mechanisms governing lodging resistance in soybeans remain elusive. In this study, we identify and characterize the Creeping Stem 1 (CS1) gene, which plays a crucial role in conferring lodging resistance in soybeans. The CS1 gene encodes a HEAT-repeat protein that modulates hypocotyl gravitropism by regulating amyloplast sedimentation. Functional analysis reveals that the loss of CS1 activity disrupts polar auxin transport, vascular bundle development, and the biosynthesis of cellulose and lignin, ultimately leading to premature lodging and aberrant root development. Conversely, increasing CS1 expression significantly enhances lodging resistance and improves yield under conditions of high planting density. Our findings shed light on the genetic mechanisms that underlie lodging resistance in soybeans and highlight the potential of CS1 as a valuable target for genetic engineering to improve crop lodging resistance and yield.

plant biology↗