Biology subjects

Jiang, X.

Publications and source records attributed to Jiang, X..

At least 145 records · Page 8Linked to original sources

bioRxiv2025

SpaFun: Discovering Domain-specific Spatial Expression Patterns and New Disease-Relevant Genes using Functional Principal Component Analysis

SpaFun is a novel, non-model-based method developed to address limitations in existing spatially variable gene (SVG) detection techniques, particularly for large-scale spatially resolved transcriptomics (SRT) datasets. These limitations include computational inefficiency, limited statistical power with increasing data size, and the inability to capture spatial heterogeneity and co-expression patterns among genes. Built on functional principal component analysis (fPCA), SpaFun identifies domain-representative genes (DRGs) with significantly better computational efficiency and greater statistical power while accounting for spatial heterogeneity and co-expression patterns among genes. We applied SpaFun to three SRT datasets and demonstrated that SpaFun outperformed state-of-the-art algorithms for identifying representative genes for tumor regions (e.g., DESeq, edgeR, and limma), as well as recently developed novel algorithms designed for spatial omics to identify the representative genes (e.g., SPARK and CSIDE). This highlights SpaFuns ability to accurately identify genes most representative of each spatial domain (e.g., tumor, immune, or stroma regions). By uncovering novel disease-relevant genes overlooked by existing algorithms, SpaFun could provide insights into new molecular mechanisms and propose innovative therapeutic strategies to improve patient outcomes. Key PointsO_LISpaFun is the first method dedicated to identifying DRGs, capturing spatially representative expression patterns within annotated tissue regions, setting it apart from all traditional SVG detection methods. C_LIO_LIIt leverages fPCA to model gene expression as a function of spatial location, avoiding reliance on predefined spatial distribution assumptions. C_LIO_LIThe non-model-based framework ensures compatibility with different SRT platforms and experimental designs, making it a scalable and widely applicable tool for SRT research. C_LI

genomics↗

bioRxiv2025

China Autism Brain Imaging Consortium: Charting Brain Growth in Chinese Children with Autism

Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition characterized by atypical brain growth. While advances in neuroimaging and openly sharing large-sample datasets such as the Autism Brain Imaging Data Exchange (ABIDE) have improved understanding of ASD, most studies focus on adolescents and adults, with early brain development-critical for diagnosis and intervention-remaining underexplored. Existing research predominantly involves Western samples, offering limited insight and generalizability into non-Caucasian populations. We introduce the China Autism Brain Imaging Consortium (CABIC) (https://php.bdnilab.com/resources/), a grassroots effort by researchers across the country to aggregate previously collected multi-site structural MRI datasets and phenotypic information from 1,451 autistic children and 1,119 typically developing children, covering an age range from early childhood to school age (1.0 - 12.92 years). Here, we present this resource and depict brain growth charts to push forward a more comprehensive understanding of the brain development in Chinese autism children. We constructed brain growth charts that reveal a developmental shift in autistic children, transitioning from early overgrowth to delayed maturation. Regional analyses identified distinct atypical trajectories across specific brain regions. Individual deviation scores quantified inter-subject variability, characterizing the heterogeneity of brain development in ASD. Comparative analyses between CABIC and ABIDE highlighted differences potentially attributable to ethnicity and culture, advancing our understanding of cross-population neurodevelopmental diversity. CABIC MRI datasets will be shared publicly to foster investigation of the potential neural mechanisms underlying ASD in non-Western populations and support efforts toward precision medicine for autistic individuals across diverse backgrounds.

neuroscience↗

bioRxiv2025

Developing Foundation Models for Predicting Viral Animal Host Range in Intelligent Surveillance

Emerging human infectious viruses originating from animals continue to pose a persistent threat to global public health. Understanding the host range of animal viruses is crucial for identifying potential spillover pathways and mitigating the risk of future pandemics. Here, we present VirHRanger, a prediction method that integrates foundation models trained on viral genome and protein sequences, alongside genomic and protein compositional traits, viral phylogeny, and protein-protein interactions. To systematically predict the animal host range, VirHRanger incorporates host taxonomy-aware neural networks trained on a comprehensive collection of animal-virus associations spanning mammals, birds, and arthropods. Within a dataset of 4,006 virus species spanning 99 viral families, our model achieved robust performance with a micro-averaged AUROC of 0.938 across all host categories, demonstrating its effectiveness in capturing generalizable host signals from viral genetic data. On a dataset of 315 novel viruses, which are associated with key reservoir animal hosts and insect vectors, VirHRanger notably outperformed the homology-based method, exhibiting a strong generalizability to novel viruses. Furthermore, VirHRanger identified host range variations among closely related viruses within the Coronaviridae family and successfully predicted the ability of SARS-CoV-2 to infect humans and other animal hosts. These findings highlight the potential of VirHRanger to transform sequencing data into timely insights for disease control during the early stages of zoonotic outbreaks.

bioinformatics↗

bioRxiv2025

Candidate transmission survival genome of Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb), a leading cause of death from infection, completes its life cycle entirely in humans except for transmission through the air. To begin to understand how Mtb survives aerosolization, we mimicked liquid and atmospheric conditions experienced by Mtb before and after exhalation using a model aerosol fluid (MAF) based on the water-soluble, lipidic and cellular constituents of necrotic tuberculosis lesions. MAF induced drug tolerance in Mtb, remodeled its transcriptome and protected Mtb from dying in microdroplets desiccating in air. Yet survival was not passive: Mtb appeared to rely on hundreds of genes to survive conditions associated with transmission. Essential genes subserving proteostasis offered most protection. A large number of conventionally nonessential genes appeared to contribute as well, including genes encoding proteins that resemble anti-desiccants. The candidate transmission survival genome of Mtb may offer opportunities to reduce transmission of tuberculosis. Significance StatementMycobacterium tuberculosis (Mtb) travels from the lungs of one person through the air to the lungs of another and survives multiple stresses en route, including changes in temperature and in concentrations of oxygen, carbon dioxide, hydrogen ions, salts and organic solutes. Here we present a genetically tractable model of transmission to begin the identification of the transmission survival genome of Mtb. We devised a fluid that mimics TB lesions, found that it protects Mtb from transmission-related stresses, associated this with the structure of the droplets as they dry and their ability to retain water, and used it to query the potential contribution of each of Mtbs genes to Mtbs survival in models of three sequential stages of transmission.

microbiology↗

bioRxiv2025

Lipid nanoparticle delivery of siRNA to dorsal root ganglion neurons to treat pain

Sensory neurons within the dorsal root ganglion (DRG) are the primary trigger of pain, relaying activity about noxious stimuli from the periphery to the central nervous system; however, targeting DRG neurons for pain management has remained a clinical challenge. Here, we demonstrate the use of lipid nanoparticles (LNPs) for effective intrathecal delivery of small interfering RNA (siRNA) to DRG neurons, achieving potent silencing of the transient receptor potential vanilloid 1 (TRPV1) ion channel that is predominantly expressed in nociceptor sensory neurons. This leads to a reversible interruption of heat-, capsaicin-, and inflammation-induced nociceptive conduction, as observed by behavioral outputs. Our work provides a proof-of-concept for intrathecal siRNA therapy as a novel and selective analgesic modality.

neuroscience↗

bioRxiv2025

Follicular mural granulosa cells stockpile glycogen to fuel corpus luteum pre-vascularization

The corpus luteum (CL) arises from the luteinization of follicular granulosa cells (GCs) and theca cells, marked by rapid progesterone elevation and angiogenesis. Intriguingly, angiogenesis lags behind progesterone elevation, creating an avascular phase during which luteal cells must fuel intensive steroidogenesis without perfusion. How the avascular CL meets this energetic demand remains a mystery. Here, we reveal a novel cellular adaptive mechanism-GC energy storage (GCES)-that resolves this enigma. We demonstrate that upon luteinization initiation, GCs enter a metabolically quiescent state yet enhance glucose uptake via SLC2A1, converting the glucose into glycogen through the hCG (LH)-MAPK-RUNX1-Insulin signaling axis. Catabolism of this glycogen reserve supplies the energy required for the avascular CL, ensuring normal luteogenesis. GCES is evolutionarily conserved across species. Genetic or pharmacological disruption of GCES or glycogenolysis induces luteal insufficiency, whereas timely glucose administration enhances GCES, improving luteal function and optimize reproductive outcome in both mouse and ovine models. In human study, orally intake of glucose post-hCG significantly augments GCES and enhances progesterone production in women. These results advance luteal physiology by uncovering a universal reproductive principle with direct clinical implications.

developmental biology↗

bioRxiv2025

Clinical and Taxonomic Characterization of a Novel Urinary Tract Pathogen Providencia lanzhouensis

BackgroundThe genus Providencia includes species of ecological and clinical significance, with some acting as opportunistic pathogens in hospital-acquired infections such as urinary tract infection (UTI). However, overlapping phenotypic traits and genetic similarities pose challenges for accurate species characterization. This study exemplifies this challenge by identifying a novel Providencia isolate through genomic analysis. ResultsIn this study, strain PAZ2 was isolated from the urine sample of a hospitalized patient in Lanzhou, Gansu Province, China. Initial mass spectrometry analysis identified the strain as Providencia alcalifaciens. It exhibits a resistance profile against antibiotics including ampicillin, tetracycline, tigecycline, polymyxin B, colistin, trimethoprim-sulfamethoxazole, and ciprofloxacin. However, whole-genome sequence analysis indicated that this strain is a novel species with an average nucleotide identity (ANI) values ranging from 79.92% to 94.73% and digital DNA-DNA hybridization (dDDH) values between 21.2% and 57.6% when compared with all known Providencia species. Furthermore, strain PAZ2 exhibited unique biochemical properties that differentiated it from all previously described species within the genus. ConclusionsGenomic and biochemical evidence supports PAZ2 as a novel Providencia species, which we named Providencia lanzhouensis sp. nov. This finding enhances the taxonomy of Providencia and underscores its clinical relevance, notably in UTIs and other nosocomial infections. Accurate identification is crucial for guiding effective treatment and preventing misdiagnosis. Further studies should investigate its pathogenicity, antimicrobial resistance, and epidemiology to inform infection control measures.

microbiology↗

bioRxiv2025

Title: Cell-autonomous and non-cell-autonomous effects of TRIM72 on ALS disease progression

Dysfunction of RNA-binding proteins, including TDP-43 and FUS, has been associated with amyotrophic lateral sclerosis (ALS); however, the underlying mechanisms are largely unknown. Here, we reported that a neuronal upregulation of TRIM72 (Tripartite Motif Containing 72) in FUS mutation knockin ALS models slows disease progression. TRIM72 interacts with Commander, a protein complex for recycling of membrane proteins, facilitating membrane repair and antioxidation. Exosomal TRIM72 is detected in ALS patient cerebrospinal fluid (CSF) and extracellular application of exosomal TRIM72 protects cell from membrane damage. In a sporadic ALS cohort, CSF TRIM72 level associates ALS disease progression. AAV-mediated neuronal expression of TRIM72 slows down the disease progressions in ALS models and in an ALS patient without adverse effects over a year treatment course. Taken together, our results suggest a universal neuronal protection of a TRIM family protein in cell-autonomous and non-cell-autonomous manners in ALS.

neuroscience↗

bioRxiv2025

Unveiling the Evolution of Antimicrobial Peptides in Gut Microbes via Foundation Model-Powered Framework

Antimicrobial resistance poses a growing threat to public health, emphasizing the urgent need for novel therapeutic strategies. Antimicrobial peptides (AMPs), short peptide sequences with diverse mechanisms of action, offer a promising alternative due to their broad-spectrum activity against pathogens. Recent advances in protein language models (PLMs) have revolutionized protein structure prediction and functional annotation, highlighting their potential for AMP discovery and therapeutic development. In this context, we present AMP-SEMiner (Antimicrobial Peptide Structural Evolution Miner), an AI-driven framework designed to identify AMPs from metagenome-assembled genomes (MAGs). By integrating PLMs, structural clustering and evolutionary analysis into the framework, AMP-SEMiner can identify AMPs encoded by small open reading frames (smORFs) and encrypted peptides (EPs), significantly expanding the discovery space. Using this approach, we identified 1,670,600 AMP candidates from diverse habitats. Experimental validation of 29 candidates revealed antimicrobial activity in 18, with 13 surpassing antibiotics in effectiveness. Further analysis of AMPs from human gut microbiomes demonstrated both conserved and adaptive evolutionary strategies, ensuring their functional efficacy in the dynamic gut environment. These findings position AMP-SEMiner as a powerful tool for the discovery and characterization of novel AMPs, with significant potential to drive the development of new antimicrobial therapies.

microbiology↗

bioRxiv2025

HeteroRepur: Efficient Modeling of Heterogeneous Disease Graph for Depression Drug Repurposing using Heterogeneous Graph Neural Networks

ObjectiveMajor Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders, yet existing treatments often result in suboptimal responses and encounter high recurrence rate. Repositioning existing medications, which often significantly reduces the required time and budget, has been demonstrated to be a promising strategy for drug discovery of multiple central nervous system (CNS) disorders. However, an efficient modeling strategy of heterogeneous semantic information among biological networks has yet to be developed for drug repurposing. Material and MethodsIn this study, we proposed HeteroRepur, by integrating heterogeneous graph neural networks to learn interaction features of Depression Drug Repurposing Graph (DDRG) and then classify drugs. ResultsThe DDRG embeddings learned by HeteroRepur accurately capture graph information, including 89 types of interaction or associations among drugs, genes, pathways, and GOs, as well as disease genetic network of MDD. In drug classification task, HeteroRepur outperforms various baseline models, including existing graph neural network approaches that do not consider heterogeneous network information. Finally, HeteroRepur predicts new candidates for treating MDD, including CNS drugs that have the potential to be extended to MDD, and dietary supplements that might benefit depression patients by elevating essential nutrient levels. ConclusionHeteroRepur outperforms traditional graph-based approaches, and can be used to rank promising drugs among complex disease networks with heterogeneous topology.

bioinformatics↗

bioRxiv2025

Trans-generational maintenance of mitochondrial DNA integrity in oocytes during early folliculogenesis

Mutations in mitochondrial DNA (mtDNA) can lead to mitochondrial and cellular dysfunction. However, recent studies suggest that there is purifying selection against mutant mtDNAs during transgenerational transmission. We investigated the mtDNA dynamics during ovarian follicle development. Using base-editing, we generated mice harboring a 3177 G>A mutation corresponding to the human Leber hereditary optic neuropathy (LHON)-related mtDNA mutation and confirmed the transgenerational reduction of mutant mtDNA. Using a mouse follicle culture system in which pathogenic mtDNA mutations were introduced in vitro followed by mtDNA sequencing and digital PCR, we found this germline heteroplasmy shift during early folliculogenesis was induced by the decrease of mutant mtDNA together with compensatory replication of wild-type mtDNA. In contrast, synonymous mtDNA mutations did not impact the mtDNA dynamics. These findings show that mice can eliminate certain pathogenic mtDNA mutations in the germline during early folliculogenesis, maintaining mitochondrial integrity across generations.

genetics↗

bioRxiv2024

FABP5 in Skin Macrophages Mediates Saturated Fat-Induced IL-1β Signaling in Obesity-Associated Psoriasis Development

High fat diet (HFD)-induced obesity increases the risk and severity of psoriasis. However, the immunoregulatory effects of different HFD-induced obesity on psoriasis pathogenesis remains poorly understood. Here, mimicking human dietary fat profiles, four HFDs - saturated, monounsaturated, omega-6 and omega-3 fats - were designed and used to induce obesity in mice. Despite comparable obesity levels across groups, only the saturated HFD exacerbated imiquimod (IMQ)-induced psoriasis. This exacerbation correlated with elevated levels of IL-1{beta}-producing macrophages, IL-17A-producing {gamma}{delta} T cells, and neutrophils within psoriatic lesions. Mechanistically, saturated fatty acids (FAs) promoted IL-1{beta}/IL-17 signaling via fatty acid-binding protein 5 (FABP5)-mediated mitochondrial FA oxidation and extracellular ATP release in skin macrophages. Deletion of FABP5, either globally or specifically in macrophages, attenuated IL-1{beta}/IL-17A signaling and alleviated IMQ-induced psoriasis. These findings identify FABP5 as a key mediator of saturated HFD-driven psoriasis via the IL-1{beta}/IL-17 axis, offering insights into the interplay between dietary fats, obesity and psoriasis. HighlightsO_LISaturated, but not unsaturated, high-fat diets (HFDs) drive the development of obesity-associated psoriasis. C_LIO_LISaturated fats enhance IL-1{beta}/IL-17 signaling in psoriatic skin. C_LIO_LIFABP5 mediates saturated fat-induced IL-1{beta} signaling by promoting ATP production and release. C_LIO_LIDeletion of FABP5 in macrophages alleviates the development of saturated HFD-associated psoriasis. C_LI Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/628705v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@93fedaorg.highwire.dtl.DTLVardef@409fa2org.highwire.dtl.DTLVardef@b08362org.highwire.dtl.DTLVardef@81abcc_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Incomplete lineage sorting of segmental duplications defines the human chromosome 2 fusion site early during African great ape speciation

All great apes differ karyotypically from humans due to the fusion of chromosomes 2a and 2b, resulting in human chromosome 2. Yet, the structure, function, and evolutionary history of the genomic regions associated with this fusion remain poorly understood. Here, we analyze finished telomere-to-telomere chromosomes in great apes and macaques to show that the fusion was associated with multiple pericentric inversions, segmental duplications (SDs), and the rapid turnover of subterminal repetitive DNA. We characterized the fusion site at single-base-pair resolution and identified three distinct SDs that originated more than 5 million years ago. These three distinct SDs were differentially distributed among African great apes as a result of incomplete lineage sorting (ILS) and lineage-specific duplication. Most conspicuously, one of these SDs shares homology to a hypomethylated SD spacer sequence present in hundreds of copies in the subterminal heterochromatin of chimpanzees and bonobos. The fusion in human was accompanied by a systematic degradation of the three divergent -satellite arrays representing the ancestral centromere creating five distinct structural haplotypes in humans. CRISPR/Cas9-mediated depletion of the fusion site in human cell lines significantly alters the expression of 108 genes, indicating a potential regulatory consequence to this human-specific karyotypic change.

evolutionary biology↗

bioRxiv2024

A Wearable Spiral Ultrasound Patch for Focused Ultrasound Peripheral Neuromodulation of Diabetic Neuropathic Pain

Diabetic foot disease, a severe complication of diabetes, frequently results in diabetic neuropathic pain, which diminishes quality of life and increases the risk of amputation. Current treatment options are limited in their effectiveness and can present adverse effects. We have demonstrated a first-of-its-kind wearable spiral ultrasound patch for focused ultrasound peripheral neuromodulation to alleviate diabetic neuropathic pain. This innovative, stretchable ultrasound device reliably delivers focused ultrasound to peripheral nerves. The devices ultrasound elements are arranged in a phyllotaxis spiral pattern, enhancing transmitted acoustic focus performance and minimizing grating and side lobes. Using a diabetic foot rat model, we confirmed peripheral neuropathy through behavioral assessments of mechanical allodynia and heat hyperalgesia, which showed significant pain relief after two weeks of ultrasound treatment. Additionally, nerve conduction velocity improved. Biological safety tests indicated no adverse effects on nerve tissues or cells. Our approach offers a non-invasive solution for managing diabetic neuropathic pain and provides critical insights into its underlying mechanisms, paving the way for more effective therapies.

bioengineering↗

bioRxiv2024

A novel and robust method for assessing mitochondrial (dys)function in healthy and diseased frozen cardiac tissue

Cardiovascular diseases are often associated with impairment in mitochondrial function detected by reduced mitochondrial oxygen consumption using high-resolution respirometry. However, existing respirometry protocols are limited by the necessity for fresh tissue samples. This study developed a method with tailored substrate-inhibitor titration (TSIT) of mitochondrial electron transport complexes (ETC) to measure mitochondrial function in frozen cardiac samples using high-resolution respirometry. Briefly, acetyl-CoA was added to fuel the tricarboxylic acid (TCA) cycle for NADH production, enabling complex I (CI)-linked respiratory assessment. NADH was then added to measure maximum CI-linked respiratory capacity, followed by rotenone and succinate to assess complex II (CII)-linked respiratory capacity. TSIT detected mitochondrial functional differences between frozen atrial and ventricular tissue, with comparable results as measured in fresh samples. It also detected cardiac mitochondrial dysfunction across various (patho)physiological mouse models (including aging, ischemia reperfusion, obesity, and CI deficiency) as well as in frozen human donor samples, highlighting its clinical potential. Furthermore, we showed the first evidence for supercomplexes (SCs) formation between ETC-SCs and the TCA cycle metabolon, underpinning TSIT feasibility. In conclusion, we established a novel, robust, sensitive and translational method (TSIT) for assessing mitochondrial (dys)function in frozen cardiac samples from various species, enabling flexible analysis of mitochondrial function in both laboratory and clinical settings.

physiology↗

bioRxiv2024

Local Haplotype Classifiers enable Efficient, Flexible, and Secure Genotype Imputation and Downstream Analyses

The decreasing cost of genotyping technologies led to abundant availability and usage of genetic data. Although it offers many potentials for improving health and curing diseases, genetic data is highly intrusive in many aspects of individual privacy. Secure genotype analysis methods have been developed to perform numerous tasks such as genome-wide association studies, meta-analysis, kinship inference, and genotype imputation outsourcing. Here we present a new approach for using lightweight haplotype classifier models to use predicted haplotype information in a flexible privacy-preserving framework to perform genotype imputation and downstream tasks. Compared to the previous secure methods that rely main on linear models, our approach utilizes efficient models that rely on utilizing haplotypic information, which improves accuracy and increases the throughput of imputation by performing multiple imputations per model evaluation.

bioinformatics↗

bioRxiv2024

A photorespiratory glyoxylate shunt in the cytosol supports photosynthesis and plant growth under high light conditions in Arabidopsis

Photorespiration, a central aspect of plant metabolism that is tightly connected to photosynthesis, functions in part to support photosynthetic performance, especially under stress conditions such as high light. However, our understanding of the mechanisms underlying the role and regulation of photorespiration in plant response to high light is limited. To identify modulators of photorespiration under high light, we isolated genetic suppressors of the photorespiratory mutant hpr1, which is defective in the peroxisomal hydroxypyruvate reductase 1. A suppressor that partially rescued hpr1 under high light was mapped to GLYR1, which encodes the cytosolic glyoxylate reductase 1 enzyme that converts glyoxylate to glycolate. Independent GLYR1 loss-of-function mutants also partially rescued hpr1 and another photorespiratory mutant, catalase 2. Our genetic, transcriptomic and metabolic profiling analyses together suggested a novel connection between cytosolic glyoxylate and a non-canonical photorespiratory route mediated by the cytosolic HPR2 enzyme, which we named the photorespiratory glyoxylate shunt. This shunt is especially critical under high light intensities when a high rate of photorespiratory flux is required and in the absence of a properly functional major photorespiratory pathway. Our findings support the metabolic flexibility of photorespiration and may help future efforts to improve crop performance under stress.

plant biology↗

bioRxiv2024

Multi-omics analysis of the mechanism of alfalfa and wheat-induced rumen flatulence in Xizang sheep

This study induced a rumen flatulence model in Xizang sheep using alfalfa (HRF) and wheat grass (MRF) to explore related mechanisms. The pH of HRF and MRF groups was lower than the natural grass group. SCFA concentrations varied in different groups. Microbial analysis showed HRF and MRF groups had lower alpha and beta diversity and different compositions. Transcriptome analysis found different numbers of differentially expressed genes in each group. Spearmans correlation analysis indicated Butyrivibrio was related to GLRX and DUOX2, and Quinella to several genes.

microbiology↗