Biology subjects

Gao, W.

Publications and source records attributed to Gao, W..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Molecular Mechanisms Underlying Human Vγ9Vδ2 T Cell Activation by Butyrophilin-3 (BTN3) Targeted Antibodies

{gamma}{delta} T cells express T cell receptors (TCRs) composed of paired {gamma} and {delta} chains. The V{gamma}9V{delta}2 T cells are the main subpopulation of {gamma}{delta} T cells in human peripheral blood, which responds to phosphoantigens (pAgs) through butyrophilins (BTN) molecules, such as BTN3A1/2/3 and BTN2A1. Antibodies targeting BTN3As, such as ICT01, can activate V{gamma}9V{delta}2 T cells independently of pAgs, although the underlying mechanism remains poorly characterized. In this study, we reveal the molecular basis of ICT01-mediated V{gamma}9V{delta}2 T cell activation using structural, biochemical, and cellular analyses. ICT01 binds to a unique region in the extracellular domain of BTN3As, destabilizing the BTN2A1-BTN3As interface and facilitating V{gamma}9V{delta}2 TCR engagement, ultimately resulting in activation of V{gamma}9V{delta}2 T cells. Our findings provide insights into the mechanism by which agonist antibodies induce {gamma}{delta} T cell activation and provide guide strategies for developing BTN-targeted immunotherapies.

immunology↗

bioRxiv2025

Phosphoantigen-Driven Dissociation of Butyrophilin Oligomers Activates γδ T Cells

{gamma}{delta} T cells represent a promising avenue for cancer immunotherapy. The V{gamma}9V{delta}2 T cell receptor (TCR), expressed by the predominant subset of {gamma}{delta} T cells, responds to phosphoantigen (pAg)-engaged butyrophilins (BTNs) on various cancer cells. However, the molecular mechanism underlying pAg-mediated activation of V{gamma}9V{delta}2 TCRs remains a subject of debate. Here, we employed an integrative approach to elucidate the mechanism of pAg reactivity in V{gamma}9V{delta}2 T cells. Our results demonstrate that BTNs form higher-order oligomers in the absence of pAg. Upon pAg binding, these oligomers dissociate into tetramers, enabling V{gamma}9V{delta}2 TCR engagement. This pAg-induced dissociation of higher-order BTN complexes is critical for pAg-mediated activation of {gamma}{delta} T cells. Our findings reveal a mechanism of BTN dissociation-driven pAg sensing, providing valuable insight for future immunotherapeutic strategies.

immunology↗

bioRxiv2025

Albumin-STING Nanocomplex Reprograms HSPCs to Antitumor Neutrophils with Enhanced MHC I Antigen Presentation for Cancer Immunotherapy

Tumor-associated immunosuppressive neutrophils, termed myeloid-derived suppressor cells (MDSCs), compromise cancer immunotherapy. They can be pathologically programmed as early the hematopoietic stem and progenitor cell (HSPC) stage by suppressing interferon signaling. Reprogramming HSPCs toward antitumor neutrophils through the stimulator of interferon genes (STING) activation offers a promising therapeutic strategy. Here, we demonstrate that an albumin-STING nanoagonist (Nano ZSA-51D) reprograms HSPCs to generate antitumor neutrophils, enhancing MHC I-mediated CD8 T cell immunity. Nano ZSA-51D activates STING-interferon signaling in HSPCs, promoting their expansion and differentiation toward granulocyte-monocyte progenitors via STING-NF-{kappa}B-IL-6 signaling. It further reprograms neutrophils into CD14ICAM-1+ subset through STING-NF-{kappa}B-TNF- signaling, enhancing tumor infiltration. These neutrophils upregulate interferon signaling and MHC I antigen presentation, boosting tumor-specific CD8 T cell responses. Adoptive transfer of Nano ZSA-51D-reprogrammed neutrophils with -PD1 therapy achieves complete colon tumor remission. Our findings provide a novel strategy to reprogram HSPCs toward antitumor neutrophils and highlight the potential of early interventions at HSPC stage to rewire neutrophil fate for cancer immunotherapy.

immunology↗

bioRxiv2025

Accurate detection and quantification of single-base m6A RNA modification using nanopore signals with multi-view deep learning

N6-methyladenosine (m6A) is a crucial epitranscriptomic mark. While Nanopore Direct RNA Sequencing (DRS) enables transcriptome-wide detection, most existing methods neglect or lack the capacity to effectively process the intrinsically variable-length raw signals generated by DRS reads.Here, we present MultiNano, a multi-view deep learning framework that converts variable-length raw signals into image-like feature representations, effectively resolving the length inconsistency problem. By integrating raw signal and basecalling features, MultiNano enables accurate and comprehensive transcriptome-wide detection of m6A modifications. Our model achieved state-of-the-art (SOTA) performance in various tasks, including site-level prediction, read-level prediction, cross-species transfer learning, and modification rate estimation. Furthermore, the false positive control strategy implemented in MultiNano significantly enhances the models robustness and predictive accuracy, offering a powerful alternative to traditional thresholding-based filtering algorithms. Collectively, our approach provides novel insights for the absolute quantification and single-base resolution of RNA modifications.

bioinformatics↗

bioRxiv2025

SVPG: A pangenome-based structural variant detection approach and rapid augmentation of pangenome graphs with new samples

Breakthrough advances in long-read sequencing technologies have opened unprecedented opportunities to study genetic variations through comprehensive pangenome analysis. However, the availability of structural variant (SV) calling tools that can effectively leverage pangenome information is limited. In addition, efficient construction of pangenome graphs becomes increasingly challenging with acquisition of larger number of samples. In this study, we present SVPG, an approach that leverages haplotype-resolved pangenome reference for accurate SV detection and rapid pangenome graph augmentation from long-read sequencing data. Compared to state-of-the-art SV callers, SVPG maintained superior overall performance across different sequencing technologies and coverages. SVPG also achieved notable improvements in calling rare and individual-specific SVs on both simulated and real somatic datasets. Furthermore, in a benchmark involving 20 samples, SVPG accelerated pangenome graph augmentation by nearly 10-fold compared to traditional augmentation strategies. We believe that this novel SVPG method, has the potential to revolutionize SV detection and serve as an effective and essential tool, offering new possibilities for advancing pangenomic research.

bioinformatics↗

bioRxiv2025

SpatioEv: Spatial evolution of protein and morphological features reveals development dynamics of cells and spatial neighbourhoods

Understanding cellular function in tissues demands sophisticated tools to decode complex microenvironmental interactions. Current spatial analysis methods often lack the comprehensive framework needed to systematically analyse cell morphology, dynamics, interactions, and extracellular matrix (ECM) architecture. We introduce SpatioEv, a unified computational framework for highly multiplexed tissue imaging that addresses these critical gaps. SpatioEv integrates automated quality control, cell phenotyping, neighbourhood identification, multi-scale spatial characterization, niche boundary analysis, ECM fiber-cell interaction mapping, and spatiotemporal trajectory inference. This pipeline enables reproducible cell annotation, reveals novel ECM-cell interactions, characterizes tissue neighbourhood boundaries, and infers developmental progressions directly from spatial data. Using this, we can identify disease-specific spatial signatures distinguishing rheumatoid arthritis from osteoarthritis, characterize diverse tumour boundary phenotypes in cancer metastases in liver, and map evolutionary trajectories in pancreatic ductal adenocarcinoma (PDAC) at single-niche resolution. Our findings highlight the significance of spatial context in shaping cell behaviour and underscore its potential to uncover emergent tissue architecture and cellular dynamics. By addressing major analytical challenges, SpatioEv provides a scalable, adaptable platform for advancing spatial biology and translational research.

systems biology↗

bioRxiv2025

Evaluation of the nano Liquid Chromatography coupled with Zeno TOF 7600 Mass Spectrometer for Cell Type-Resolved Spatial Proteomics

In this study, we systematically evaluated the nanoLC-Zeno TOF platform using data-independent acquisition (DIA) and identified 3,142 to 7,059 protein groups from 1 to 200 ng of standard K562 digest. Additionally, a targeted acquisition strategy detected 184 peptides with enhanced signal using Zeno activation. To achieve spatial cell-type resolved proteomics, we developed a workflow integrating image-guided laser capture microdissection for analysis of gastric cancer tissue. A 30-minute nanoLC gradient facilitated the quantification of 2,514 proteins from 0.2 mm{superscript 2} regions representing cancer cells, cancer-associated fibroblasts (CAFs), and immune cells, as defined by multiplex immunohistochemistry. This spatial proteomics approach revealed cellular heterogeneity within the tumor microenvironment of a clinical gastric cancer sample, and targeted validation identified differential expression of 12 cancer-associated proteins comprising 103 peptides between cancer cell-enriched and CAFs-enriched regions. This workflow offers a practical strategy for spatial visual proteomic analysis in clinical tissue samples.

cancer biology↗

bioRxiv2025

Highly sensitive and scalable time-resolved RNA sequencing in single cells with scNT-seq2

Understanding gene expression dynamics requires resolving newly synthesized RNAs from pre-existing pools at single-cell resolution. Here, we present scNT-seq2, a highly sensitive and scalable method for time-resolved single-cell RNA sequencing. By systematically optimizing the second-strand cDNA synthesis (2nd SS) step, we substantially improved read alignment rates, reduced background mutations, and enhanced library complexity compared to the original scNT-seq 1. Benchmarking in 4sU-labeled K562 cells demonstrated that scNT-seq2 accurately quantifies newly synthesized transcripts and preserves the gene level RNA turnover. The enhanced sensitivity enables robust detection of dynamic, cell-cycle state specific genes, such as S-phase regulators. Together, scNT-seq2 provides an efficient and versatile tool for dissecting transcriptional dynamics across diverse biological systems at single-cell resolution.

genomics↗

bioRxiv2025

Peptides alleviate cognitive impairment by inhibiting and disassembling amyloid-beta aggregates in Alzheimer disease

Alzheimers disease (AD) is a devasting neurodegenerative disorder characterized by {beta}-amyloid formation, further exacerbated by RIPK1/RIPK3 necrosome-induced programmed necrosis (necroptosis). We previously showed that the RIPK1/RIPK3 necrosome forms a functional amyloid complex using its RIP homotypic interaction motifs (RHIMs). Here, we discovered that the core RIPK1/RIPK3 necrosome shares strikingly structural similarity to the C-terminal region of {beta}-amyloid (A{beta}42), and the RHIM-derived tetrapeptides (IQIG or VQVG) directly inhibit A{beta} aggregation, disassemble preformed A{beta} fibrils (PFFs), and reduce RIPK1 polymerization. Also, the peptides exhibit effective membrane permeability and could reduce A{beta}40 or A{beta}42-induced neural death and TNF-induced necroptosis in SH-SY5Y cells. IQIG and VQVG injected by ICV increase learning and memory abilities by reducing A{beta} plaques and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 double-transgenic mice. Mechanistically, the peptides directly interact with A{beta} to block A{beta} aggregation and alleviate microglia-mediated neuroinflammation. Strikingly, single-cell RNA sequencing revealed that the peptides-treated AD transgenic mice restored neuronal homeostasis with increased GABAergic neurons and decreased glutamatergic neurons. Furthermore, total cell-cell interaction strength increased while the AD risk gene Apoe expression decreased in the specific oligodendrocyte subtype of peptides-treated AD mice. Thus, our findings revealed that the peptides could improve cognition and memory capabilities and serve as promising structural templates for potential drugs against AD.

neuroscience↗

bioRxiv2025

From Pan-Life Phase Insights to PhaseHub: Analyzing Condensate Complexity

Macromolecular condensation is crucial in biological signaling pathways that regulate development and adaptation processes. However, lacking conserved residues in disordered region of condensate proteins hampers alignment-based analyses of their evolutionary trajectory. To gain a comprehensive overview of phase-separating protein evolution across the Tree of Life, we analyzed phase-separating proteins of proteomes from 1,106 species. Eukaryotes and prokaryotes showed high contrast in need for phase-separating proteins and with a clear genome size-dependent correlation. Evolutionary success appears to hinge on the balance between functional condensation and avoiding harmful aggregation-prone biophysical signatures, such as certain amino acid homorepeats embedded in molecular grammar. We also identified potential phase separation-regulated signaling hubs across kingdoms by integrating phase-separation-positive proteins with protein abundance and interactome data across four model eukaryotic species. Consequently, we created PhaseHub (https://phasehub.sbs.ntu.edu.sg/), a user-friendly interface that explores key scaffold proteins and binders to pinpoint associated partners and potential multicomponent phase separation hubs. TeaserAnalyse phase separation behavior of 1,106 species across kingdoms on proteome level reconstruct the evolutional history of protein condensation.

systems biology↗

bioRxiv2025

Saddle Curvature Association of nsP1 Facilitates the Replication Complex Assembly of Chikungunya Virus in Cells

The replication of positive-sense RNA viruses, including the pathogenic SARS-CoV-1 and -2, DENV, and ZIKV, often takes place in curved cellular membrane compartments of tens to hundreds of nanometers in diameter within host cells. The non-structural proteins (nsPs) of viruses are found to critically control the formation and maintenance of such unique nanoscale membrane structures. However, the molecular mechanism underlying the association and assembly of nsPs around curved membranes has remained elusive, due to the technical difficulties of imaging the nanoscale interaction in live cells. In this study, we leveraged vertically aligned nanostructures to define membrane curvatures in live cells and investigated the assembly of viral nsPs on these curved membranes. Using Chikungunya virus as a model system, we found that its nsP1 was preferentially bound to and stabilized around positively curved membrane sites and the preference became more apparent as the radius of curvature decreased to 150 nm or smaller. This preferential accumulation was mainly attributed to the hydrophobic residues on recently identified membrane association loops (MA loops) of each nsP1 monomer. Molecular dynamics simulations further confirmed the improved binding kinetics and stability of nsP1 on positively curved membranes, especially when a 12-mer ring was formed by the nsP1 dodecamer. More interestingly, a saddle curvature association was enabled by the 3D coordination of nsP1 monomers along the dodecamer ring, where the MA loops of individual nsP1 monomers sensed a wide range of the positively curved membrane in the x-z plane while the rigid nsP1 dodecamer ring stabilized the negative curvature in the x-y plane. Its strong coupling to the saddle curvature fulfilled the need to constrain the neck of the membrane spherule for viral replication. Strikingly, productive CHIKV replication exhibited strong enrichment on patterned nanostructure array, proving the effectiveness of membrane curvature-guided assembly of the functional replication complex. Our findings revealed that the cell membrane facilitated the local enrichment of viral nsPs in a curvature- dependent manner. It opens up membrane curvature modulation as a new dimension to dissect the formation and regulation of membrane compartments for viral replication.

biophysics↗

bioRxiv2025

Reference-guided genome assembly at scale using ultra-low-coverage high-fidelity long-reads with HiFiCCL

Population genomics using short-read resequencing captures single nucleotide polymorphisms and small insertions and deletions but struggles with structural variants (SVs), leading to a loss of heritability in genome-wide association studies. In recent years, long-read sequencing has improved pangenome construction for key eukaryotic species, addressing this issue to some extent. Sufficient-coverage high-fidelity (HiFi) data for population genomics is often prohibitively expensive, limiting its use in large-scale populations and broader eukaryotic species and creating an urgent need for robust ultra-low coverage assemblies. However, current assemblers underperform in such conditions. To address this, we propose HiFiCCL, the first assembly framework specifically designed for ultra-low-coverage high-fidelity reads, using a reference-guided, chromosome-by-chromosome assembly approach. We demonstrate that HiFiCCL improves ultra-low-coverage assembly performance of existing assemblers and outperforms the state-of-the-art assemblers on human and plant datasets. Tested on 45 human datasets ([~]5x coverage), HiFiCCL combined with hifiasm reduces the length of misassembled contigs relative to hifiasm by an average of 21.19% and up to 38.58%. These improved assemblies enhance germline structural variant detection, reduce chromosome-level mis-scaffolding, enable more accurate pangenome graph construction, and improve the detection of rare and somatic structural variants based on the pangenome graph under ultra-low-coverage conditions.

bioinformatics↗

bioRxiv2025

SIMIT-seq: a bead-free, scalable microfluidic platform for single cell mRNA sequencing with ultrahigh cell-indexing rate

SIMIT-seq is a bead-free, scalable microfluidic platform designed for high-efficiency single-cell mRNA sequencing. Conventional microfluidic-based single-cell RNA sequencing platforms rely heavily on barcoded beads and intricate co-encapsulation schemes, often constrained by double Poisson limitations and the complexities of bead synthesis. In contrast, SIMIT-seq eliminates the need for beads entirely by employing a deterministic, orthogonal barcoding strategy within a two-dimensional micro-well array. This platform achieves an impressive single-cell indexing rate of 96.6% without the need for complex microfluidic operations. Here, we describe the design and fabrication of the SIMIT-seq platform, outline its workflow for transcript capture and library preparation, and demonstrate its application in profiling K562 cells. Our results validate both the high fidelity of molecular barcode immobilization and the systems capability to support downstream single-cell mRNA sequencing. SIMIT-seq offers a cost-effective and scalable alternative for single-cell transcriptomics, providing a promising foundation for future single-cell omics applications.

bioinformatics↗

bioRxiv2025

Knock-out of Tpm4.2/actin filaments alters neuronal signaling, neurite outgrowth and behavioral phenotypes in mice.

Tropomyosins (Tpm) are master regulators of actin dynamics through forming co-polymers with filamentous actin. Despite the well-understood function of muscle Tpms in the contractile apparatus of muscle cells, much less is known about the diverse physiological function of cytoplasmic Tpms in eukaryotic cells. Here, we investigated the role of the Tpm4.2 isoform in neuronal processes including signaling, neurite outgrowth and receptor recycling using primary neurons from Tpm4.2 knock-out mice. Live imaging of calcium and electro-physiology data demonstrated increased frequency, yet reduced strength of single neuron spikes. Calcium imaging further showed increase in neuronal networks. In vitro assays of Tpm4.2 knock-out neurons displayed impaired recycling of the AMPA neurotransmitter receptor subunit GluA1. Morphometric analysis of neurite growth showed increased dendritic complexity and altered dendritic spine morphology in Tpm4.2 knock-out primary neurons. Behavioral analysis of Tpm4.2 knock-out mice displayed heightened anxiety in Open field test whilst Elevated Plus maze displayed heightened anxiety only in females. A sex-dependent phenotype was also seen in the Social Preference test with impaired social memory and socialization in female Tpm4.2 knock-out mice, whilst male and female knock-out mice had impaired recognition memory in a Novel Object Recognition test. Our study depicts the multi-faceted role of the Tpm4.2 isoform and its co-polymer F-actin population in neurons, with potential implications for better understanding diseases of the nervous system which involve actin cytoskeleton dys-function.

neuroscience↗

bioRxiv2025

Integrated single-cell and spatial multiomic analysis reveals widespread reactivation of developmental programs in diseased human hearts

The first organ to develop in utero, the human heart undergoes significant changes during development and must sustain its function over a lifetime. To better characterize molecular changes in human cardiac cell-types across sex, aging, developmental and disease, we analyzed single nucleus RNA sequencing (snRNA-seq) datasets from 299 donors, identifying many more differentially expressed genes (DEGs) across developmental and disease states than by sex and age. In cardiomyocytes and most non-cardiomyocyte cell types, developmental and disease DEGs showed significant overlap. Cardiac development and disease were associated with convergent changes in non-cardiomyocyte intercellular communication, including TGF{beta} signaling, but differences in cell-type proportions. By integrating snRNA-seq with 106 snATAC-seq datasets, we reveal potential transcriptional factors driving fetal reactivation in disease. Finally, using spatial transcriptomics data, we identify that fetal reactivation is highly localized in niches. This work offers the largest multimodal, cell-type resolved interrogation of the human heart, providing insights into convergence in development and disease.

genomics↗

bioRxiv2025

RNAhub - an automated pipeline to search and align RNA homologs with secondary structure assessment

The complexity in the generation of RNA multiple sequence alignments and assessment of the accuracy of such alignments contributes to the challenges in the utilization of RNA alignments in diverse integrative methods. RNAhub is a freely available user-friendly web server for a reliable generation of RNA multiple sequence alignments and the detection of the presence of structural RNA utilizing evolutionary information. This web-based tool, developed by the integration of existing computational approaches, takes an RNA sequence as input and automatically retrieves and aligns sequences homologous to the input (query) RNA sequence through an iterative and structure-agnostic approach. Based on the alignment, this tool statistically assesses whether the query RNA sequence has a conserved RNA structure using covariation analysis. The web server allows the user to efficiently search the sequence of interest against carefully curated, ready-to-use genomic databases to produce a multiple sequence alignment. Using this alignment, our tool either detects the presence of a conserved structural RNA, finds evidence against the presence of a conserved structure, or cannot make any assessment due to a lack of sequence diversity in the alignment. The web server is freely available at https://rnahub.org. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC="FIGDIR/small/642701v3_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@540f6forg.highwire.dtl.DTLVardef@c15e53org.highwire.dtl.DTLVardef@117ced2org.highwire.dtl.DTLVardef@b679c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

Mineralocorticoid Receptor Antagonism Reduces Atrial Arrhythmias Post-Cardiac Surgery and Attenuates Atrial Stress Responses to Cardioplegic Arrest

BackgroundNew postoperative atrial fibrillation (POAF) occurs in about 40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We examined the impact of preoperative MRA use on POAF and also examine the atrial cell type impacted by MRA treatment during cold cardiac preservation. MethodsRetrospective study of 19,042 patients who underwent cardiac surgery at Mayo Clinic in Minnesota, and performed 1:3 propensity matching to obtain 298 patients on preoperative MRA matched to 894 who were not. We also separately matched patients using preoperative diuretics. Single-nuclei RNA sequencing (snRNA-seq) examined MRAs effects on different atrial cell types in canrenone (water soluble MRA) treated human donor hearts undergoing cold preservation followed by ex-vivo reperfusion and compared gene expression to the atria of patients with AF. ResultsPropensity matched preoperative MRA group had less new onset POAF (19.8% vs 31.5%, P<0.001). To account for the possibility that preoperative diuretic use and volume reduction may impact POAF, we propensity matched 298 preop diuretic users that included MRA use to another 894 patients who used a non-MRA diuretic preoperatively. Those who used preoperative MRA similarly had a lower incidence of POAF (19.8% vs 33.2%, P<0.001). No survival difference was present between the propensity matched groups that used preoperative diuretics (P=0.079). Preoperative MRA use also reduced the development of paroxysmal and chronic AF at 6 years of follow up. From our snRNA-seq data, we identified a subpopulation of atrial cardiomyocytes (CM2) that had high MR expression where canrenone suppressed the increase in MR target gene expression associated with cold preservation-reperfusion. These MR targets were conversely elevated in patients with chronic AF. Canrenone also suppressed other cardiac preservation associated genes that show elevated expression in atrial macrophages and pericytes from chronic AF atria. ConclusionsOur studies show that preoperative MRA use is associated with 40% reduction in POAF as well as lowering long standing AF development by about 41%. Our cold cadiac preservation-reperfusion model showed that canrenone reduced expression of MR target genes associated with chronic AF, particular in cardiomyocytes with important roles in electrical conduction. Clinical PerspectiveO_ST_ABSWhat is New?C_ST_ABSO_LIThis study shows that preoperative use of mineralocorticoid receptors antagonists (MRA) is associated with a reduced incidence of new onset perioperative atrial fibrillation after cardiac surgery utilizing cardiopulmonary bypass. C_LIO_LIWe show that preoperative MRA use is associated with a lower incidence of developing more chronic paroxymal or sustained atrial fibrillation. C_LIO_LIAddition of canrenone, a clinically utilized water soluble MRA, to cardioplegia solution used during cardiac preservation can attenuate atrial inflammatory reponses and reduce signaling through molecular pathways that promote atrial fibrillation. C_LI What are the clinical implications?O_LIPerioperative use of MRAs may be considered to reduce early postoperative atrial fibrillation as well as lowering the risk of developing more chronic atrial arrhythmias. C_LIO_LIThese findings support pursuing a clinical trial to determine the impact of MRA use on atrial arrhythmias following cardiac surgery in the setting of cardiopulmonary bypass with cold cardiac preservation. C_LI

molecular biology↗

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↗