Biology subjects

Cai, W.

Publications and source records attributed to Cai, W..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Stromal Gasdermin D-mediated Pyroptosis Drives Maladaptive CD4⁺ T-cell Remodeling in Tet2-Deficient Hematopoiesis

An inflammatory bone marrow microenvironment is increasingly recognized as critical in myeloid disease evolution, yet how stromal inflammation interfaces with adaptive immunity remains poorly defined. Here, we show that stromal pyroptosis drives mutation-specific myeloid expansion by coordinating monocytic remodeling and CD4 T-cell activation. Genetic ablation of gasdermin D in the bone marrow stroma suppressed stromal pyroptosis and attenuated Tet2-deficient myeloid expansion. Tet2 deficiency skewed monocyte and macrophage differentiation toward an activated, antigen-presenting state that interacted with pyroptotic stromal cells to promote expansion of a distinct CD4 T-cell population. These cells expressed canonical T follicular helper markers (Bcl6, Cxcr5, Il21, and Cd40l) together with interferon-responsive and tissue-interaction programs, consistent with an inflammation-adapted TFH-like state. CD40L produced by these cells reinforced the expansion of Tet2-deficient monocytes and macrophages, establishing a feed-forward stromal-immune circuit. Disruption of this axis through stromal gasdermin D deficiency or CD40L blockade attenuated myeloid expansion in vivo. Consistent with these findings, patients with isolated TET2 loss-of-function mutations exhibited CD4 T-cell skewing and CD40L+ T-cell-rich tertiary lymphoid structures in the bone marrow. Together, these data identify a pyroptosis-dependent stromal-immune axis that links early myeloid inflammation to maladaptive remodeling of adaptive immunity and reveals a context-dependent therapeutic vulnerability in Tet2-deficient hematopoiesis.

cancer biology↗

bioRxiv2026

Latent brain state dynamics predict early amyloid accumulation and cognitive impairment

Amyloid-{beta} (A{beta}) accumulation is a continuous process central to pathological aging that begins decades before cognitive impairment emerges. While subthreshold A{beta} levels have been linked to future decline in cognitive control, the neural mechanisms connecting this early accumulation to its neurocognitive impact are poorly understood. Brain circuit dynamics, which are essential for cognitive function, may offer a sensitive lens into these initial pathological changes. Here, we tested whether brain state dynamics could serve as sensitive markers for cognitive impairment at an early stage of A{beta} burden. Using the Bayesian Switching Dynamic System (BSDS) model, we identified 4 distinct latent brain states from high-temporal-resolution (800 ms) fMRI data acquired from 116 older adults, including 72 cognitively normal (CN) individuals and 44 with mild cognitive impairment (MCI), during an N-back working-memory task. Adopting a dimensional approach, we examined how latent brain state dynamics relate to early amyloid burden, cognitive performance, and clinical symptoms. While A{beta} levels failed to differentiate clinical groups or predict clinical symptoms and task performance, the dynamics of latent brain states proved highly sensitive to both early A{beta} accumulation and cognition. Canonical correlation analysis revealed a significant relationship between brain state dynamics and early A{beta} burden. Furthermore, the temporal properties of brain states were significantly predictive of working memory performance in CN individuals, a relationship that was selectively disrupted in the MCI group. The features of brain dynamics can also successfully predict cognitive impairment. Our findings establish brain state dynamics as sensitive neural markers of initial A{beta} accumulation and early cognitive impairment, offering a new framework for developing predictive models to identify individuals at risk for future cognitive decline.

neuroscience↗

bioRxiv2026

Symbiotic Escherichia coli strains can better colonize host stinkbugs and outcompete natural symbiotic bacteria, but confer less fitness benefits

The stinkbug Plautia stali harbors essential gut symbiotic bacteria of the genus Pantoea, whose natural strains differ in cultivability and host benefits. Using this system, we evaluated how laboratory-evolved and genetically-engineered symbiotic Escherichia coli strains compete against native Pantoea symbionts and how they influence host fitness. In single infection assays, the native uncultivable symbiont Sym A conferred the highest host performance, whereas the evolved (CmL05G13) and artificial ({Delta}cyaA) symbiotic E. coli strains supported host survival at levels comparable to cultivable Pantoea symbionts (Sym C-F). In competitive co-infection assays, the symbiotic E. coli strains generally showed unexpectedly strong colonization ability. CmL05G13 outcompeted all the cultivable symbionts Sym C-F and even displaced the native uncultivable symbiont Sym A, whereas {Delta}cyaA and the nonsymbiotic control E. coli {Delta}intS were dominated by Sym A at the adult stage. Despite their superior infection competitiveness, the symbiotic E. coli strains provided limited reproductive benefits, behaving as "cheater-like" associates. They were able to invade and dominate the symbiotic organ but failed to match the fitness contributions of native symbionts. These results demonstrate that the experimentally evolved E. coli can rapidly acquire strong colonization ability surpassing that of the natural symbionts that have coevolved with P. stali in nature. At the same time, the mismatch between infection success and host fitness benefits highlights potential evolutionary conflicts and provides an experimental model for studying the dynamics of cheating, mutualism, and symbiont replacement in vertically transmitted symbioses. IMPORTANCEUnderstanding how novel symbionts invade and displace long-term mutualists is central to the evolution of symbiosis. This study demonstrates that Escherichia coli, originally a nonsymbiotic bacterium, can rapidly evolve potent colonization ability and even outcompete native Pantoea symbionts of the stinkbug Plautia stali. Meanwhile, these competitive E. coli strains confer markedly lower reproductive benefits compared with the native symbionts that have developed intimate mutualistic association with host P. stali over evolutionary time, revealing a striking decoupling between infection success and host fitness. This finding highlights the potential for cheater-like microbes to invade vertically transmitted symbioses and destabilize coevolved partnerships. By combining experimental evolution, controlled co-infections, and quantitative analyses, the P. stali-E. coli experimental symbiotic system provides a powerful model for studying the mechanisms and evolutionary dynamics of mutualism, cheating, and symbiont replacement.

microbiology↗

bioRxiv2026

Binary-SPA: A Reference-Free Method for Cell Annotation in High-Resolution Spatial Transcriptomics

Accurate cell type annotation remains a major challenge in high-resolution spatial transcriptomics analysis. Current approaches primarily rely on label transfer from single-cell RNA sequencing (scRNA-seq) reference datasets or marker-based annotation of transcriptionally defined clusters. While these methods are widely used, they have critical limitations. Label transfer approaches depend on the availability of a well-matched scRNA-seq reference. Marker-based annotation methods often suffer from accuracy and limited coverage. To address these challenges, we developed Binary-SPA, a computational framework for cell-type annotation of high-resolution spatial transcriptomics data. Binary-SPA performs annotation in two stages. First, a binary classification step identifies high-confidence cells using predefined marker sets. These confidently annotated cells are then used as an internal reference for anchor-based label transfer in the second stage. Binary-SPA outperforms conventional marker-based annotation approaches and existing label transfer methods across multiple high-resolution spatial transcriptomics platforms, preservation methods, and tissue types. While label transfer methods achieve high accuracy only when same-tissue scRNA-seq references are available, and decline substantially when relying on independent datasets, Binary-SPA matches this performance with 100% annotation coverage while eliminating the need for external reference data entirely. Binary-SPA demonstrates robust performance even in challenging specimens such as bone marrow biopsies, and validation against matched COMET protein expression data confirmed strong concordance between transcriptomic- and protein-based cell identities. Binary-SPA thus provides a robust, reference-free solution for spatial transcriptomics annotation with broad applicability to research and clinical specimens.

genomics↗

bioRxiv2026

FluNexus: a versatile web platform for antigenic prediction and visualization of influenza A viruses

Influenza A viruses continuously undergo antigenic evolution to escape host immunity induced by previous infections or vaccinations, consequently causing seasonal epidemics and occasional pandemics. Antigenic prediction and visualization of influenza A viruses are crucial for precise vaccine strain selection and robust pandemic preparedness. However, a user-friendly online platform for these capabilities remains notably absent, despite widespread demand. Here, we present FluNexus (https://flunexus.com), the first-of-its-kind, one-stop-shop web platform designed to facilitate the prediction and visualization of the antigenic change in emerging variants. FluNexus features a data preprocessing module for hemagglutinin subunit 1 (HA1) and hemagglutination inhibition (HI) data across three major public health threat subtypes (H1, H3 and H5). Meanwhile, FluNexus provides an interactive interface for online antigenic prediction and offers practical guidance for researchers. Most notably, FluNexus offers the visualization of influenza A virus antigenic evolution, providing intuitive insights into its antigenic dynamics. Specially, FluNexus proposes a novel manifold-based method for positioning antigens and antisera, generating accurate antigenic cartographies even with sparse HI data. By alleviating the programming burden on biologists, FluNexus supports more informed decision-making in vaccine strain selection and strengthens surveillance and pandemic preparedness. HighlightsO_LIFluNexus features a data preprocessing module for HA1 and HI data spanning the H1, H3, and H5 subtypes. C_LIO_LIFluNexus facilitates online antigenic prediction utilizing ten state-of-the-art antigenic prediction tools, and offers practical guidance based on a comparative evaluation of their performance. C_LIO_LIFluNexus provides a visualization module for mapping antigenic evolution of influenza A viruses, incorporating a novel manifold-based method for antigenic cartography. C_LI

bioinformatics↗

bioRxiv2026

Exercise-Induced Epoxy-Eicosanoids Promote Cardiomyocyte Proliferation and Post-Infarction Repair via NR4A1

BACKGROUNDMyocardial infarction (MI) causes irreversible cardiomyocyte loss that exceeds the adult hearts regenerative capacity, leading to adverse remodeling and heart failure. While exercise provides cardiovascular protection, the mechanisms underlying exercise-induced cardiac repair remain unclear. METHODSPlasma levels of free fatty acids and polyunsaturated fatty acid metabolites were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RNA sequencing was performed to identify differentially expressed genes and enriched pathways. NR4A1 was knocked down in mice via tail vein injection of AAV9 carrying shRNA targeting NR4A1 (AAV9-shNR4A1). The role of 17,18-EEQ was evaluated by continuous subcutaneous infusion via osmotic minipump; the involvement of the cAMP-PKA-CREB axis was assessed using specific pharmacological inhibitor. Molecular analyses included ELISA, immunofluorescence staining, QPCR, and western blotting. Additionally, clinical samples were collected from 36 endurance-trained athletes and 30 sedentary individuals (age 18-22, male) for comparative analysis. RESULTSHere we demonstrate that preventive aerobic training promotes post-MI cardiomyocyte proliferation and confers cardioprotection by reducing fibrosis area and improving cardiac function. Targeted lipidomics revealed that exercise elevates circulating epoxyeicosatetraenoic acids (EEQs), particularly 17,18-EEQ; osmotic pump delivery of 17,18-EEQ mimicked the protective effects of exercise, reducing infarct burden and enhancing proliferation markers (Ki67, pH3, Aurora B). Transcriptomic analysis identified NR4A1 as the most prominent up-regulated mRNA under exercise induction; AAV9-mediated NR4A1 knockdown abolished exercise-mediated cardioprotection and proliferative benefits, establishing NR4A1 as essential for exercise-driven repair. Phosphoproteomic profiling revealed that 17,18-EEQ activates the PKA-CREB pathway to induce NR4A1 expression; pharmacological inhibition of adenylyl cyclase, PKA, or CREB phosphorylation reversed EEQ-mediated cardioprotection and proliferation, confirming pathway necessity. Dietary supplementation with eicosapentaenoic acid (EPA), the metabolic precursor of 17,18-EEQ, amplified exercise-induced cardioprotection by enhancing EEQ biosynthesis. CONCLUSIONOur study identifies 17,18-EEQ as an exercise-derived exerkine that promotes cardiomyocyte proliferation and post-MI repair through a PKA-CREB-NR4A1 signaling axis, advancing our understanding of exercise cardioprotection and myocardial regeneration mechanisms while providing novel therapeutic targets for cardiac intervention. What IS New?O_LIAerobic exercise enhances post-myocardial infarction cardiac repair by upregulating the cardio-protective lipid mediator 17,18-EEQ and its downstream effector NR4A1. C_LIO_LI17,18-EEQ promotes cardiomyocyte proliferation and cardiac repair through activation of the cAMP-PKA-NR4A1 signaling axis. C_LIO_LICombining aerobic exercise with omega-3 fatty acid supplementation synergistically improves cardiac remodeling and functional recovery after ischemic injury. C_LI What Are the Clinical Implications?O_LITargeting endogenous cardiomyocyte proliferation represents a promising therapeutic strategy for cardiac regeneration after ischemic injury. C_LIO_LIDietary supplementation with omega-3 fatty acids may be a clinically feasible approach to amplify exercise-induced cardioprotection and improve outcomes after myocardial infarction. C_LI

physiology↗

bioRxiv2026

Empagliflozin alleviates doxorubicin-induced cardiotoxicity by suppressing oxidative stress via modulation of the JNK/Nrf2 signaling pathway

Doxorubicin (DOX) treatment increases the risk of myocardial dysfunction and heart failure, in which oxidative stress plays a central role. Empagliflozin (EMPA) has been shown to benefit heart failure patients, yet its underlying mechanism remains unclear. In this study, we showed that EMPA treatment improved cardiac function, ameliorated structural remodeling, and increased survival in DOX-treated mice. Furthermore, EMPA reduced DOX-induced reactive oxygen species (ROS) overproduction and myocardial injury. Through functional analysis overlapping DIC- and EMPA-regulated genes, we identified the involvement of JNK signaling in addition to redox pathways. Subsequent investigations demonstrated that EMPA restored redox homeostasis by inhibiting JNK activation, reactivating NRF2 and its downstream antioxidant proteins HO-1, NQO1, GPX4, and SOD2 both in vivo and in vitro. These protective effects were abolished by the Nrf2 inhibitor ML385 or the JNK activator anisomycin. Collectively, our findings indicate that EMPA protects against DOX-induced cardiotoxicity by modulating the JNK/Nrf2 signaling and attenuating oxidative stress. This study provides a rationale for further investigation of EMPA as a potential therapeutic strategy for chemotherapy-associated cardiac injury. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/697595v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@16743d4org.highwire.dtl.DTLVardef@96495borg.highwire.dtl.DTLVardef@aa343dorg.highwire.dtl.DTLVardef@4ba18c_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2025

The glutamine transporter Slc38a1 is widely expressed in the embryonic neurogenic niches and impacts neuronal volume, survival, and morphology

The amino acid glutamine, and its derivatives glutamate and GABA, are pivotal for neurogenesis. However, how glutamine is mechanistically supplied to the cells in the neurogenic niches and its broader impact on neurodevelopment, remain poorly characterized. The Solute carrier family 38 member 1 (Slc38a1) exhibits high affinity for glutamine and accumulates glutamine in select cells. We investigated whether Slc38a1 is essential for neurogenesis and whether it has an impact on brain structure and function. Slc38a1 mRNA transcript and protein are widely expressed in the embryonic brain, including in the dorsal pallium and sub-pallium. At embryonic day 15.5, Slc38a1 localizes in neuronal stem cells in the ventricular zone in the forebrain, while it localizes in mature neurons in the sub-ventricular zone of the hindbrain. In the adult brain, Slc38a1 is not detected in neuronal stem cells in the sub-granular zone, however, it is highly enriched in mature local parvalbumin+ and somatostatin+ interneurons and ependyma. Analyses of single-cell RNA sequencing data further reveal that both the number of Slc38a1-expressing cells and the average transcript level of Slc38a1 are significantly higher in embryo brain cells compared to adults. In the embryo, Slc38a1 transcripts are particularly enriched in immature neuronal lineages and embryonic oligodendrocyte precursor populations, whereas in the adult, expression is more prominent in neural progenitor cells and radial glia. Disruption of Slc38a1 in mice impacts body weight, brain size and glutamatergic neuronal volume, while dendritic arborization is diminished and cellular life span is shortened. Altogether, Slc38a1 is essential for normal neurodevelopment, indirectly regulates adult neurogenesis in the sub-granular zone and influence neuronal morphology and cell viability.

neuroscience↗

bioRxiv2025

Developmental deviations of structural connectivity in youths with ADHD predict symptom and treatment outcomes

Attention-deficit/hyperactivity disorder (ADHD) lacks validated biomarkers to track symptom development or guide treatment selection in youth. We quantified individual deviations from normative age-related trajectories of white-matter structural connectivity (SC) across two independent cohorts: 6,687 typically developing and 1,114 ADHD scans from the ABCD study, and 292 typically developing and 482 ADHD participants from a Chinese cohort. Youth with ADHD showed pronounced SC deviations, especially in higher-order association pathways. A subset of connections showed ADHD-specific developmental reductions in deviations beyond typical developmental patterns, and these changes mediated the age-related decline in ADHD symptoms. Longitudinal within-individual analyses demonstrated that decreases in deviation over two years tracked symptom improvement. Baseline deviations also predicted 12-week treatment response to atomoxetine, but not methylphenidate, and follow-up imaging revealed treatment-related reductions in deviation. Together, these findings identify SC deviation as a robust developmental biomarker with prognostic and theragnostic relevance for ADHD, supporting precision care through risk stratification, individualized pharmacotherapy selection, and objective monitoring of treatment effects.

neuroscience↗

bioRxiv2025

Host EV derived lipids promote malaria parasite development via mosquito fatty acid oxidation

Malaria parasites must transition between mammals and mosquitoes, but how they adapt to such distinct environments is unclear. We show that blood from infected mammals buffers this environmental shift by packaging parasite-induced signals into extracellular vesicles (EVs). EVs internalized by mosquito midgut increases expression of VLCAD and raises levels of a 22-carbon fatty acid, driving fatty acid breakdown and acetyl-CoA production. The parasite exploits this metabolic shift to synthesize its own lipids during oocyst growth. Stable isotope tracing confirmed that13C4-labelled behenic acid is degraded and incorporated into parasite fatty acids. Lipidomic profiling further revealed that ceramides enriched in the EVs are key mediators. These findings identify a mechanism by which host bood-derived EVs reprogram mosquito lipid metabolism to promote parasite transmission.

microbiology↗

bioRxiv2025

Shared and distinct neural signatures of inhibitory control deficits in attention-deficit/hyperactivity disorder and autism

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share deficits in inhibitory control, yet direct comparisons of their neurobiological underpinnings remain sparse and are often confounded by comorbidity. We examined shared and distinct abnormalities in brain activation and circuit connectivity associated with inhibitory control in non-comorbid ADHD and ASD. MethodsBrain activity and hyperdirect pathway connectivity during inhibitory control were examined in children with non-comorbid ADHD (age: 11.1{+/-}0.24y) and children with non-comorbid ASD (age: 11.1{+/-}0.39y), compared with typically developing (TD) children (age: 10.9{+/-}0.09y), and benchmarked against healthy adults (age: 24.1{+/-}1.26y), using fMRI stop-signal task data. ResultsBoth ADHD and ASD groups showed reduced activation in salience and frontoparietal network regions alongside increased activation in default mode network (DMN) regions, consistent with triple-network dysfunction. These activation deficits were more pronounced in ASD, whose activation profile also diverged most from adults. At the circuit level, only ASD showed abnormal hyperdirect connectivity, involving insula-STN and preSMA-STN pathways and further reflected in a composite insula/IFG-STN connectivity measure, indicating broader cortical-STN disruption. Importantly, across all children, reduced salience/frontoparietal relative to DMN engagement correlated with greater parent-reported inhibitory control deficits, and in ASD, individual differences in insula/IFG-STN connectivity showed the same association, highlighting the behavioral relevance of both network- and circuit-level abnormalities. ConclusionsADHD and ASD share network-level but differ in circuit-level abnormalities underlying inhibitory control deficits. Together, these insights advance the neurobiology of inhibitory control in ADHD and ASD and provide potential targets for neuroscience-informed interventions addressing both shared and disorder-specific mechanisms.

neuroscience↗

bioRxiv2025

Prolonged Starvation Drives Epigenetic Remodeling: Insights from DNA Methylation Profiling in the Aquatic Pathogen Flavobacterium columnare

Nutrient scarcity is a common environmental stressor encountered by bacteria. Despite its significance in bacterial virulence and physiology, the underlying epigenetic mechanisms of bacterial adaptation to prolonged starvation remain poorly understood. In this study, we utilized the latest Nanopore R10.4.1 sequencing technology to comprehensively characterize the genome-wide methylation landscape of the freshwater fish pathogen Flavobacterium columnare following long-term starvation at different temperatures. Our results revealed significant methylation plasticity under starvation conditions, characterized by distinct motif-dependent patterns. Notably, demethylation of the 6mA-modified CAYNNNNNRTG motif emerged as a robust epigenetic signature of starvation adaptation, with functional enrichment of genes involved in pathways for translation and metabolism, suggesting the role of this methylase in regulating essential cellular functions under starvation stress. Additionally, another 6mA-modified GCAGA motif exhibited temperature-dependent variation, indicating its potential role in temperature-specific response. Together, this study provides novel insights into the epigenetic mechanisms underlying the bacterial adaptation to nutrient deprivation and establishes a valuable methodological reference for bacterial epigenetics analysis utilizing advanced Nanopore sequencing technologies.

microbiology↗

bioRxiv2025

Unraveling the Molecular and Physiological Roles of Signal Peptide Peptidase A (SppA) in Flavobacterium columnare

Columnaris disease, caused by Flavobacterium columnare, represents one of the most economically devastating bacterial infections in global freshwater aquaculture. Despite its significant impact, the molecular mechanisms underlying F. columnare pathogenesis remain largely unexplored due to the challenge in targeted genomic manipulation. Signal peptide peptidase A (SppA) plays a crucial role in bacterial protein secretion by degrading residual signal peptides after protein translocation, yet its function in F. columnare physiology and virulence has not been characterized. Here, we employed a targeted gene deletion approach to investigate the role of sppA in F. columnare. The {Delta}sppA mutant exhibited pleiotropic phenotypes including increased outer membrane vesicle (OMV) production (3.8-fold higher compared to the wild type), reduced biofilm formation, and loss of gliding motility. Transcriptomic analysis of the {Delta}sppA mutant revealed significant upregulation of genes involved in membrane stress response and efflux pump system, including algU, osmC and the genes in the MacAB-TolC efflux system, compared to the wild-type state. Importantly, the artificial infection experiment demonstrated the mutants significantly attenuated virulence in freshwater Medaka (Oryzias latipes), with a 20% higher survival rate of fish compared to the wild type. Our findings reveal that SppA is essential for maintaining membrane homeostasis in F. columnare and serves as one of the virulence factors during columnaris infection. These results provide important insights into the biological function of the sppA gene in F. columnare and highlight the complex relationship between bacterial protein secretion, membrane integrity, and pathogenesis. ImportanceF. columnare causes significant economic loss in freshwater aquaculture. Understanding the molecular mechanisms underlying F. columnare pathogenesis is crucial for developing new ways for disease control. Our findings reveal that SppA is essential for gliding motility, adhesion, biofilm formation and maintaining membrane homeostasis in F. columnare, which serves as one of the virulence factors during columnaris infection. In addition, outer membrane vesicles (OMVs) and MacA/MacB/TolC tripartite efflux pump served as a compensatory mechanism for enhanced peptide metabolites secretion to manage the accumulation of misfolded proteins resulting from the sppA deficiency. These results provide important insights into the biological function of the sppA gene in F. columnare and highlight the complex relationship between bacterial protein secretion, membrane integrity, and pathogenesis.

genetics↗

bioRxiv2025

Study of Sex Differences in the Whole Brain White Matter Using Diffusion MRI Tractography and Suprathreshold Fiber Cluster Statistics

Sex-specific characteristics demonstrate a substantial influence on the brain white matter (WM), suggesting distinct structural connectivity patterns between females and males. Diffusion MRI (dMRI) tractography is an important tool in assessing WM connectivity and brain tissue microstructure across different populations. Whole brain tractography analysis for group statistical comparison is a challenging task due to the large number of WM connections. This work studies whole-brain WM connectivity differences between females and males using dMRI tractography. We study a large cohort of 707 subjects from the Human Connectome Project Young Adult dataset. By applying a well-established fiber clustering pipeline and a suprathreshold fiber cluster statistical method, we analyze tracts in the cerebral cortex and understudied pathways like those connecting to the cerebellum. We identify several tracts with significant sex differences in terms of their fractional anisotropy and/or mean diffusivity. These include deep tracts like the arcuate fasciculus, corticospinal tract, and corpus callosum, superficial tracts in the frontal lobe, and cerebellar tracts. Finally, correlation analysis reveals that these WM differences are linked to a range of neurobehavioral measures, with the strongest and most consistent associations observed for motor function, suggesting motor circuits as a potential key focus for future research.

neuroscience↗

bioRxiv2025

SpatialFuser: A Unified Deep Learning Framework for Spatial Multi-Omics Data Integrative Analysis

Recent advances in spatial multi-omics technologies provide unprecedented opportunities to interpret molecular features in tissue microenvironments, but integrative analysis across heterogeneous datasets remains challenging. Here we present SpatialFuser, a deep learning framework for integrative analysis of unpaired spatial multi-omics data across epigenomics, transcriptomics, proteomics, and metabolomics. SpatialFuser consists of three coordinated modules: MCGATE, a Multi-head Collaborative Graph Attention auToEncoder that learns multi-scale spatial representations to decipher fine-grained spatial heterogeneity beyond predefined spatial neighbourhoods; an optional geometric pre-matching module that provides coarse initialization under tissue geometry mismatch; and an iterative matching-fusion module that couples geometry-constrained optimal transport matching with contrastive-learning-guided modality fusion for cross-slice alignment and integration. Systematic benchmarks demonstrate superior performance and reliability compared with existing state-of-the-art methods in spatial domain identification, cross-slice alignment, and multi-omics integration. Applications to real datasets illustrate that SpatialFuser resolves precise spatial molecular patterns, reveals developmental dynamics, and recovers complementary signals across modalities. Cross-resolution integration of weakly correlated modalities by our method further uncovers previously obscured biological variation. The generalizability and versatility of our framework enable customized analytical scenarios and potential extension for emerging omics. HighlightsO_LIA unified deep learning framework for spatial multi-omics integrative data analysis C_LIO_LISuperior performance against state-of-the-art methods in spatial identification, alignment, and multi-omics integration C_LIO_LIUnprecedented cross-modality analysis scenarios to offer a holistic view of spatial multi-omics C_LIO_LIComprehensive framework design with generalizability and versatility for customized scenarios and potential extension C_LI

bioinformatics↗

bioRxiv2025

Modeling 3D Mesoscaled Neuronal Complexity through Learning-based Dynamic Morphometric Convolution

Accurate reconstruction of neuronal morphology from three-dimensional (3D) light microscopy is fundamental to neuroscience. Nevertheless, neuronal arbors intrinsically exhibit slender, tortuous geometries with high orientation variability, posing significant challenges for standard 3D convolutions whose static, axis-aligned receptive fields lack adaptability to such complex morphology. To address this, we propose the Dynamic Morph-Aware Convolution (DMAC) framework, which incorporates inherent geometric priors into convolution by jointly adapting both the shape and orientation of the kernel. This enables morphology-aware feature extraction tailored to arborized and variably oriented neuronal trajectories. Specifically, we first apply dynamic tubular convolutions to bridge the structural mismatch between isotropic convolution kernels and the slender morphology of neurons. To sufficiently accommodate the 3D orientation variability of neuronal branches, we further introduce a rotation mechanism that dynamically reorients the tubular kernel via two learnable angles (elevation and azimuth), enabling precise alignment with local neuronal directions. We validate our method through extensive experiments on four mesoscaled neuronal imaging datasets, including two from the BigNeuron project (Drosophila and Mouse) and two additional benchmarks (NeuroFly and CWMBS). Our approach consistently outperforms state-of-the-art methods, achieving average improvements of 5.4% in Entire Structure Average (ESA), 6.9% in Different Structure Average (DSA), and 7.5% in Percentage of Different Structure (PDS). These results demonstrate the effectiveness of our proposed DMAC in capturing complex morphological variations and enhancing structural fidelity across diverse mesoscaled neuronal morphologies.

neuroscience↗

bioRxiv2025

A Cattle BodyMap of Transcriptome across 52 Tissues and 3 Developmental Stages Reveals New Genetic Insights into Beef Production Traits

Cattle are important livestock that provide essential meat and milk resources. However, a comprehensive analysis of gene expression, alternative splicing (AS), and RNA editing across various organs and developmental stages in cattle has not been reported. This study aims to create a comprehensive transcriptomic BodyMap across various tissues and developmental stages, integrating this information into genomic predictions of beef production traits. We created a comprehensive transcriptomic BodyMap using 400 samples collected from 52 organs of newborn, young, and adult cattle, and estimated their contributions to genetic variance and genomic predictions for 23 beef production traits in 1476 beef cattle. We cataloged the expression of 25,530 annotated genes, 28,533 novel long non-coding RNAs (lncRNAs), 215,754 AS events, and 3,093,058 A-to-I RNA-editing sites. Integrating transcriptome BodyMap with 23 beef production traits, we found lncRNAs influenced traits like rib-eye area and carcass length, while RNA editing associated with chunk roll weight and daily gain. We observed trait-relevant tissues between different stages, including the differential expressed genes of cerebellum, longissimus muscle, and testis between newborn and adult stages are more relevant to beef production traits. The tissue-specific genes and development-associated genes in several tissues could improve the reliability of genomic prediction in beef production traits. We developed Cattle BodyMap Transcriptome Database (https://cattlegenomics.online/cattle_bodymap) to retrieve, analyze, and visualize gene expression, lncRNA, splicing and RNA editing data. Our results demonstrated the potential of using transcriptome data as a valuable resource for genomic selection and breeding programs in beef cattle. Additionally, our transcriptome BodyMap serves as a valuable resource for biological interpretation, functional validation, and genomic improvement in livestock.

genomics↗

bioRxiv2025

DNA Divers: volunteer-based eDNA capture for local and global marine biodiversity monitoring

Volunteer-based biodiversity recording is a powerful source of scalable data yet to be used to its full potential by the scientific community. Coastal ecosystems are varied and diverse, making it difficult for managers to identify flexible methods for monitoring biological components. Emerging technologies such as environmental DNA (eDNA) analysis are promising for measuring aquatic biodiversity, yet most management organizations lack personnel and capacity to collect molecular data. Here we investigate, together as professional and non-professional scientists, the efficacy of a quasi-passive eDNA capture technique. Volunteer SCUBA divers and snorkelers used low-cost materials, namely cotton medical gauze, to capture eDNA via swimming. We compared this method to conventional eDNA capture techniques in an aquarium and nature, collectively iterating the field and laboratory procedures to improve feasibility. With a small (< 30) network of volunteers, we detected 275 unique teleost and elasmobranch species from varied marine habitats spanning 90 degrees of latitude. The swimming motion of divers was more effective than stationary soaking and the fish communities sampled by divers were comparable to that of conventional eDNA samples. The ease of this technique matched by the eagerness and generosity of volunteers presents an untapped, viable approach for scaling multi-species marine eDNA monitoring as well as an avenue for improving science literacy. Data availabilityhttps://zenodo.org/records/14853820?token=eyJhbGciOiJIUzUxMiJ9.eyJpZCI6ImYxMTlhODFiLTI3NGYtNDQ2Ni05MDYyLTIyOTlkNWVhY2FkNiIsImRhdGEiOnt9LCJyYW5kb20iOiIwYmZlMzJhMWU0YWZkM2ZhMWEwYTE0NmY0ZWM5YWZkNSJ9.0R7GJjVJLEuq-UJVKA1CcMT8LCTamv3GEvPl-5ItzP10pFRd-cAzAr_Q5ggjEewZUtByHjBu-eSegWWlLAx_Rw

ecology↗