Biology subjects

Chen, Q.

Publications and source records attributed to Chen, Q..

At least 19 recordsLinked to original sources

bioRxiv2026

IL-27 Reduces Cell-Surface LDLR in Human Macrophages and Restricts VSV-G-Pseudotyped HIV infection

The low-density lipoprotein receptor (LDLR) is a major cellular receptor for vesicular stomatitis virus glycoprotein (VSV-G), which is widely used to pseudotyped virus vectors. A replication incompetent VSV-G-pseudotyped HIV (VSV-G-HIVLuc) has been used in HIV infection studies. Although IL-27-polarized macrophages induce multiple antiviral genes and resist replication-competent HIV infection, their impact on VSV-GHIVLuc infection has not been studied. Here, we evaluated the role of IL-27 polarization on VSV-G-HIVLuc infection. Infection was monitored by luciferase activity. Cell-surface LDLR was analyzed by flow cytometry. LDLR transcripts and protein expression were quantified by qRT-PCR and Western blotting, respectively. Viral binding was assessed by measuring cell-associated p24 antigen, while post-entry events were evaluated by quantifying late reverse-transcription products. VSV-G-HIVLuc infection in IL-27-polarized M-CSF-induced macrophages (27M-Mac) and IL-27-polarized GM-CSFinduced macrophages (27GM-Mac) was reduced to 5.8{+/-}0.4% and 5.9{+/-}2.1%, respectively (both p<0.0001), compared to unpolarized macrophages. 27M-Mac and 27GM-Mac reduced cell-surface LDLR to 38.3{+/-}2.6% (p<0.01) and 31.4{+/-}3.2% (p<0.01). Western blotting showed that total LDLR protein decreased to 48{+/-}0.8% in 27M-Mac (p<0.01), whereas 27GM-Mac showed no significant change. However, LDLR transcripts increased approximately 1.6-1.9-fold following IL-27 treatment in both macrophage types (p<0.01). Viral binding to 27M-Mac decreased modestly, while binding to 27GM-Mac decreased significantly to 67.5 {+/-} 7.5% of that to GM-Mac (p<0.05, n=3). In contrast, late reverse-transcription products decreased to 23{+/-}2.1% (p<0.0001) and 44{+/-}1.5% (p<0.0001). These findings demonstrate that IL-27 downregulates cell-surface LDLR expression in macrophages despite increasing LDLR transcript abundance, suggesting that IL-27 restricts VSV-G-pseudotyped Lentiviral infection through both receptor-associated and additional post-entry mechanisms.

immunology↗

bioRxiv2026

Hybrid Semantic-Lexical Retrieval for Source-to-CDE Mapping in the NCI caDSR

Accurate mapping of local source data elements to standardized common data elements (CDEs) is critical for biomedical data integration but is challenged by short, abbreviated, and heterogeneous source descriptions. We constructed a benchmark of approximately 69,000 expert-linked source-to-CDE mappings from the National Cancer Institute\textquotesingle s caDSR and evaluated multiple bi-encoder models with two-stage fine-tuning. Here we developed a hybrid retrieval system combining semantic bi-encoder retrieval, CDE Match-inspired keyword retrieval, cross-encoder scoring, and supervised reranking. This system achieved Recall@5 ranging from 0.802 to 0.972 across internal and five distribution-shifted holdouts, outperforming the other evaluated methods on five of six datasets and approaching ceiling performance on the sixth dataset (GDC). These results demonstrate the effectiveness and robustness of integrating semantic and lexical evidence for source-to-CDE mapping, supporting improved interoperability and reuse of biomedical metadata across diverse clinical and research contexts.

bioinformatics↗

bioRxiv2026

Structural analysis reveals three families of bacterial tRNA mimics

Comparative genomics has identified over 1,000 candidate structured RNA motifs, yet most remain functionally uncharacterized. Here, we combine crystallography, comparative analysis, and bacterial genetics to identify three families of bacterial tRNA-like RNAs. The skipping-rope RNA adopts an L-shaped fold resembling tRNA despite distinct secondary-structure connectivity and tertiary interactions. In Clostridioides difficile, the skipping-rope RNA RCd1 is abundantly expressed and processed into a highly stable RNA species. RCd1 overexpression suppresses sporulation, whereas its deletion enhances early spore formation, supporting a role in sporulation control. Guided by the skipping-rope structure, we identify a conserved architectural core and use it to recognize additional candidate tRNA mimics. Crystal structures of DUF2693-FD and salivarius-1 RNAs confirm a shared tRNA-like scaffold assembled through distinct interaction networks. Together, these findings expand the repertoire of bacterial tRNA mimics and establish a structural framework for recognizing shared architectures among uncharacterized ncRNAs, linking one such family to bacterial developmental regulation.

biochemistry↗

bioRxiv2026

Dark diversity reveals assembly constraints across trophic levels in large-scale grassland restoration

1. Grassland biodiversity restoration efforts have largely focused on re-establishing diverse plant communities, with less attention paid to higher trophic levels such as invertebrates. 2. We established a controlled, field-scale restoration experiment across twelve lowland grassland sites in Switzerland in close collaboration with farmers. We manipulated seed addition (hay transfer, directly harvested seeds, or multiplied seed mixtures) and soil disturbance (shallow or deep tillage), with treatments applied to meadows covering, on average, 0.5 ha. Four to six years after restoration, we quantified the components of species richness change (lost, persisting, gained from site surroundings, and gained from donors), and estimated dark diversity (species that are absent from a location but could potentially occur there) for plants, Auchenorrhyncha and Orthoptera. 3. Compared to plants, invertebrates exhibited greater species turnover, with higher proportions of species lost and gained from the surroundings, but much lower contributions from the donor meadows. However, species persistence was high across taxa. Restoration operations strongly influenced components of species richness change in plants but had weaker effects on invertebrates. In particular, multiplied seed mixtures + deep tillage had the highest proportion of plant species not transferred, suggesting that many species in the seed mixture were poorly suited to local conditions. In both plants and Auchenorrhyncha, components of species richness change were strongly mediated by site characteristics, with initial species richness in both receiver and donor emerging as the strongest predictors. 4. Within each taxonomic group, 41% of species not transferred from the donor belonged to the dark diversity, suggesting substantial unrealized restoration potential. Restoration operations impacted dark diversity for plants and Auchenorrhyncha but not for Orthoptera. In plants, dark diversity was substantially lower under multiplied seed mixtures + deep tillage than under other treatments. The probability of a species belonging to dark diversity was associated with specific leaf area in plants and initial relative abundance in Auchenorrhyncha. 5. Synthesis and applications. Components of species richness change were influenced by both restoration operations and site characteristics, with their relative importance varying among taxa, underscoring the need for multi-taxon restoration strategies.

ecology↗

bioRxiv2026

sORF-Trans2MS: a two-module deep learning framework for sORF translation and MS-supported microprotein prediction

Ribosome profiling is widely used to identify translated small open reading frames (sORFs), but existing prediction models often generalize poorly to newly collected sORF datasets. In addition, many microproteins with strong mass spectrometry (MS) evidence lack support in public Ribo-seq resources, suggesting that Ribo-supported sORF and MS-supported microprotein detection may represent complementary prediction tasks. Here, we developed sORF-Trans2MS, a two-module deep learning framework for predicting Ribo-supported sORFs and MS-supported microproteins. Module I uses RNA-FM representations for upstream, ORF, and downstream regions with a Transformer encoder for Ribo-supported sORF translation prediction. Module II integrates pretrained RNA-FM representations of RNA context with ESM-2 protein representations using multi-scale CNN encoders for predicting translated microproteins supported by MS but not Ribo-seq data. Module I was trained on 9,579 Ribo-supported sORFs and matched background sORFs, while Module II used 14,697 MS-supported (MS++Ribo-) microproteins and matched backgrounds. Module I achieved an AUROC of 0.870 internally and 0.930 on an independent GENCODE dataset. Ablation analysis highlighted upstream RNA context, including a distinct signal around 50 nt upstream of AUG. Module II achieved an AUROC/AUPR of 0.804/0.797 internally and 0.785/0.773 on an independent mass spectrometry dataset. Model interpretation highlighted upstream RNA context and the protein N terminus, while literature-supported microproteins further illustrated the complementary roles of the two modules. Overall, sORF-Trans2MS improves prediction and generalization of Ribo-supported sORFs and extends computational discovery to MS-supported candidates that are not represented in current public Ribo-seq resources.

bioinformatics↗

bioRxiv2026

De novo design of flexible protein interactions with GuideFlip

De novo design of protein binders requires a target structure. However, for flexible targets, such as intrinsically disordered proteins, this structure does not exist until the binder has stabilized the interaction. Such targets are therefore difficult for methods that separate structure generation from sequence design. We introduce GuideFlip, which co-designs structure and sequence through guided discrete flow matching: binder residues are assigned progressively while the complex is re-predicted at each step, allowing the evolving interface to affect the design process. GuideFlip reduces the hydrophobic bias of direct AlphaFold optimization and improves in silico success rates over existing approaches. We release a database of binder candidates for 177 human disordered proteins. Experimentally, we obtain de novo binders to the C-terminus of -synuclein and the disordered amino terminus of RBX1 with hit rates of 13.5% and 41.7%, respectively, and we confirm the epitopes of selected binders by NMR and mutagenesis. Applying GuideFlip to flexibility on the binder side, we design a nanobody that binds the agonist-bound {beta}1-adrenergic receptor in the active state, but not the receptor in its inactive state, with a 75% hit rate and cryo-EM structure confirming the design. GuideFlip enables protein design where bound structures emerge only upon binding.

biophysics↗

bioRxiv2026

The Flame Retardant Triphenyl Phosphate Induces Varying Responses in Genetically Diverse Mouse Induced Pluripotent Stem Cells

Genetic variation impacts biological response to chemical and environmental exposures, contributing to differences in resistance or susceptibility. Forward genetic screens of genetically diverse cell populations can be used to identify the precise genetic variants that drive response variation. Cell lines from laboratory mouse genetic reference populations like the Diversity Outbred (DO) population are well powered for genetic mapping. Diverse stem cell panels are especially beneficial for studying early developmental effects of chemical exposures like triphenyl phosphate (TPHP), an organophosphate flame retardant linked to adverse developmental effects, including altered cell cycle in stem cells. Self-renewal and pluripotency are defining properties of stem cells during development; therefore, it is important to understand how chemicals like TPHP may alter these critical characteristics. To better understand the influence of genetic variation on TPHP exposure response, we utilized a genetically diverse panel of DO induced pluripotent stem cells (DO iPSCs). Our analyses characterize interline variation in gene expression through differential gene expression analysis and expression quantitative trait locus (eQTL) mapping. We identified genomic loci that contribute to variation in gene expression following TPHP exposure, including a regulatory hotspot on chromosome 15. Gene set enrichment highlighted several pathways affected by TPHP including lipid metabolism, steroid hormone signaling, and cell cycle. Our study shows that genetic variation modulates the effects of TPHP on gene expression and cell cycle in stem cells. Additionally, our work demonstrates that genetically diverse cell panels like the DO iPSC resource offer a tractable and scalable approach for identifying the genetic determinants of chemical toxicity.

genomics↗

bioRxiv2026

Anticipated distractor processing relies on distinct representational states before and after distractor onset in visual working memory

Successful goal-directed behavior requires limiting the impact of salient information that is irrelevant to current goals. When distractors can be anticipated, task-irrelevant information may be encoded before it appears, yet the functional role of such anticipatory coding remains unclear. Does advance coding of irrelevant content itself support protection of visual working memory (VWM), or does effective control depend on how distractor representations evolve after entering processing? Here, using human EEG and multivariate decoding, we addressed this question by tracking distractor representations across temporal, spectral, and spatial dimensions. The distractor category was cued in advance and reliably decoded before physical onset, demonstrting content-specific anticipatory coding. However, the strength of this coding was not associated with behavioral protection. Instead, distractor processing showed a structured transition from relatively stable and temporally generalizable pre-distractor coding to more temporally unstable and time-specific post-distractor coding. Feature-level analyses further showed that distractor representations were shifted into a different representational configuration relative to representations of the same features when they served as task-relevant targets, indicating post-distractor reformatting of irrelevant content. Spectral and spatial analyses further showed that pre- and post-distractor coding relied on distinct frequency and scalp-topographic signatures. Strong anticipatory coding was associated with reduced subsequent post-distractor instability, whereas behavioral protection was associated with post-distractor instability even when pre-distractor metrics were taken into account. Together, these findings suggest a temporally coordinated control mechanism in which anticipatory coding may specify the upcoming irrelevant content, whereas post-onset reformatting may implement control by placing that content into a less stable representational state to reduce behavioral interference.

neuroscience↗

bioRxiv2026

Substrate recognition and ion coupling mechanism of the human VIAAT

Inhibitory neurotransmission, essential for neural circuit homeostasis and proper neurological function, depends on the efficient sequestration of {gamma}-aminobutyric acid (GABA) and glycine into synaptic vesicles. This critical process is mediated exclusively by the vesicular inhibitory amino acid transporter (VIAAT). Despite extensive biochemical and physiological investigation, the molecular mechanism governing VIAAT-mediated transport has remained incompletely understood. Here, we determined structures of human VIAAT in multiple functional states, including apo, GABA-bound, and glycine-bound states, as well as apo state in chloride-free condition. VIAAT adopts a classical LeuT-fold and we elucidated how its large, electronegative binding pocket accommodates both GABA and glycine. Moreover, we resolved two previously unidentified chloride-binding sites. Through integrative molecular dynamics simulations and functional mutagenesis, our results support roles for chloride and the conserved residue E213 in substrate binding and proton-coupled transport. Together, our findings establish a structural framework for VIAAT-mediated inhibitory neurotransmitter transport that illuminates the molecular basis of inhibitory synaptic transmission and provides a foundation for understanding VIAAT dysfunction in epilepsy and related neurodevelopmental disorders.

neuroscience↗

bioRxiv2026

A cross-kingdom interactome predicted by AlphaFold3 reveals a DNF2-centered interface required for symbiotic accommodation

Legumes convert atmospheric nitrogen into ammonium through symbiotic bacteria housed in root nodules, yet the molecular interactions between rhizobial and host proteins inside nodules remain poorly understood. Here we employed AlphaFold3 to construct a cross-kingdom interactome between Medicago truncatula and its symbiont Sinorhizobium meliloti. Screening more than 217,000 protein pairs yielded 7,137 putative interactions, providing a valuable resource for the broader symbiosis community. Within this network, we focused on DEFECTIVE IN NITROGEN FIXATION 2 (DNF2), a host protein required for rhizobial persistence within nodules. We showed that DNF2 localizes to the peribacteroid space and associates with previously uncharacterized secreted rhizobial proteins (SRPs), suggesting it may function as a hub for host-symbiont communication. Notably, knockout of two DNF2-interacting proteins, SRP86 and SRP485, results in white, nitrogen-fixation-deficient nodules with abnormal symbiosomes and elevated expression of senescence-associated genes, closely phenocopying the dnf2 loss-of-function mutant. Together, our findings define a DNF2-SRP molecular framework underlying symbiotic accommodation, and illustrate the potential of AI-guided interactome mapping to uncover molecular mechanisms of plant-microbe interactions with relevance to sustainable agriculture.

plant biology↗

bioRxiv2026

A patient-centric therapeutic paradigm uncouples prostate cancer suppression from systemic metabolic collapse

The clinical benefits of cancer therapies are often compromised by the tolerable adverse effects that impair systemic organismal health and may evolve into latent life threats. Here, we identified profound abiraterone-induced but androgen-independent metabolic perturbations in prostate cancer patients and developed Lifehug-9892 to balance tumor therapy with systemic metabolic homeostasis. By integrating population cohorts with high-resolution metabolomics, we demonstrate that abiraterone induces profound systemic lipidomic dysregulation, characterized by the massive, pathological accumulation of desmosterol. Abiraterone inhibits but stabilizes DHCR24, leading to a metabolic trap in patients showing elevated levels of both desmosterol and cholesterol. Desmosterol accumulation is highly lipotoxic, potently triggering endothelial cell senescence and necrosis, macrophage foam cell formation, murine atherosclerosis, and hepatic senescence. To mechanistically uncouple and therapeutically rescue this systemic metabolic collapse, Lifehug-9892 was rationally designed to selectively retain on-target CYP17A1 inhibition while completely sparing DHCR24 function. Lifehug-9892 maintains potent tumor-suppressive activity while fully preserving the desmosterol-cholesterol metabolic axis and preventing systemic cardiovascular and hepatic damage. Our study uncovers a critical mechanistic link between drug-induced metabolic dysregulation and organismal health in cancer patients, providing a biochemical framework for developing patient-centric targeted therapies that preserve host homeostasis.

cancer biology↗

bioRxiv2026

Pto evolved from malectin-like RLKs phosphorylates AvrPtoB to promote Prf-mediated immunity in Solanum pimpinellifolium

Bacterial speck, caused by Pseudomonas syringae pv. tomato (Pst), is a devastating disease of tomato that severely limits global tomato productivity. Understanding the molecular mechanisms underlying Pst and tomato is essential for developing disease resistant varieties. Here, we demonstrate that Pto, the first disease-resistance gene conferring recognition of a specific pathogen, phosphorylates Pst type III effector AvrPtoB at serine 335 site. This post-translational modification triggers the dissociation of the Prf immune complex, enhancing immune signaling and reducing bacterial pathogenicity. Furthermore, evolutionary analyses indicate that Pto-associated proteins originated from malectin-like receptor kinases (MLRs) through loss of the extracellular domain. Crucially, we identified two key amino acid substitutions, Arg158 and Glu258 in Pto, which replace the ancestral lysine residues in MLRs (SpHREK1-1, SpHERK1-2 and SpHERK1-3). These substitutions stabilize Pto by preventing degradation mediated by AvrPtoB's E3 ubiquitin ligase activity. Our findings reveal a novel mechanism, by which Pto phosphorylates a bacterial effector to trigger enhanced immunity and elucidate the key evolutionary adaptations that have shaped Pto into a stable resistance protein.

plant biology↗

bioRxiv2026

Contrasting selective pressures shape human pepsinogen A gene copy-number variation across Eurasia

Diet has repeatedly shaped human genomes, yet adaptation of protein digestion remains poorly understood. Using 1,348 haplotype-resolved assemblies, we reconstructed the structural evolution of the human pepsinogen A (PGA) locus and found a west-to-east increase in copy-number across Eurasia that tracked regional reliance on plant-derived protein. Modern and ancient genomes further revealed a recent selective sweep in the East but signatures of balancing selection in the West. We traced this divergence primarily to expansion of PGA34A, the most proteolytically active paralog in vitro, and showed that recurrent nonallelic homologous recombination continually generated structural diversity in this locus. Independent PGA expansions were also enriched in plant-dominant mammals. These findings link paralog-specific dosage variation in protein digestion to dietary adaptation across human populations and diverse mammalian lineages.

genomics↗

bioRxiv2026

PanSVmerger: a flexible pipeline for merging multiallelic structural variants in pangenome graphs

SummaryPangenome graphs capture extensive genetic diversity but introduce analytical challenges due to the redundant representation of structural variations (SVs). While existing tools effectively address cross-sample redundancy or cross-locus redundancy, none specifically target the intra-locus allelic redundancy inherent to pangenome graphs. Here, we present PanSVmerger, an open-source tool designed to consolidate redundant multiallelic SVs within individual loci using three complementary clustering strategies: adaptive k-mer-based Jaccard distance, global alignment distance via VSEARCH, and length distribution. Validation on HPRC pangenome data demonstrates that PanSVmerger effectively reduces multiallelic complexity (e.g., AC [≥] 3 loci from 62.4% to 4.7% using Strategy A) with a modest trade-off: Recall decreased from 97.13% to 93.58%, while precision improved from 94.95% to 96.56%, yielding an overall F1-score of 95.05%. These results demonstrate that PanSVmerger effectively consolidates redundant allele representations with only a minimal loss of sensitivity, making it well-suited for downstream applications that require clean, non-redundant variants. Availability and implementationPanSVmerger is implemented in Python 3.8+ and freely available under the MIT license at GitHub: https://github.com/tingting100/PanSVmerger. The software requires vcflib, bcftools, and optionally VSEARCH. Comprehensive documentation and tutorials are provided.

bioinformatics↗

bioRxiv2026

Plasma titration provides a physical ruler for cross-platform proteomics

Plasma proteomics is expanding across platforms and cohorts, and integrating these data for AI demands comparability at the protein level, not merely concordant associations1,2. Affinity and MS platforms use distinct probes (antibodies, aptamers, or peptides) and signal readouts, yielding contradictory cross-platform results3,4. Without a known quantitative truth, we cannot distinguish biology from measurement distortion, leaving no gold standard for integration. Here we introduce Plasmix--a plasma reference suite with predefined male:female ratios (M, 1:0; Y, 3:1; P, 1:1; X, 1:3; F, 0:1)--and show that preserving this quantitative titration gradient, not just technical repeatability, predicts cross-platform concordance and identifies protein measurements suitable for integration. Profiling Plasmix across five platforms (Olink, SomaScan, NULISA, AAgAtlas, and MS-DIA) and 12 protocols across 17 batches, we found discordance is dominated by signal generation, not sample identity, and platforms distort signals in a protein-specific manner. Crucially, proteins retaining the titration response showed stronger agreement in an independent cohort; anchoring to the Plasmix midpoint (P) via sample-to-reference ratios reduced distortions, extending harmonizable coverage by 10-20%. Plasmix thus provides a physical ruler to benchmark accuracy, identifying genuinely integrable measurements before pooling datasets or training AI models--a critical bottleneck for plasma proteomics.

molecular biology↗

bioRxiv2026

MMMAS: A Mendelian Mismatch Matrix Analysis System for Deterministic Pre-Screening of Germplasm Collections

Pedigree errors, duplicate accessions, and undocumented kinship limit the effective use of large genebank collections. Existing tools such as CERVUS and COLONY require allele-frequency estimates and return relationship-level assignments, providing no collection-wide view of Mendelian consistency. We developed the Mendelian Mismatch Matrix (MMM) framework and its open-source implementation, MMMAS (Mendelian Mismatch Matrix Analysis System). We applied MMM to apple (Malus x domestica; 1,085 accessions, 15 SSRs) and sweet cherry (Prunus avium; 383 accessions, 13 SSRs) datasets from the German Fruit Genebank. MMM converts pairwise Mendelian mismatch numbers (Mmn) into an N x N symmetric matrix, from which we derive four collection-scale indices (Mmin, the Mendelian minimum mismatch number; Mavg, the Mendelian average mismatch number; Mzmp, the Mendelian zero-mismatch partner number; Mmmd, the Mendelian mismatch-mode duplication index) and the Mendelian Exhaustive Stratification (MES) grading system. Apple showed a gradient-type structure (Mendelian Grade-gap Index, MGI = 0.125), sweet cherry a broken-type structure (MGI = 0.545). The Mmin-Mavg strategy identified 20 and 10 distinct accessions in apple and sweet cherry, including the scab-resistance donor Malus x floribunda 821 (Rvi6) and the fire-blight donor M. x robusta 5. The Mmmd index flagged one literature-confirmed pair of duplicate genotypes in sweet cherry. Of CERVUS-confirmed parent-offspring pairs, 97.31% in apple and 100% of high-confidence pairs in sweet cherry fell within Mmn <= 1. Mzmp rankings matched documented breeding history, with 'Cox Orange' (Mzmp = 57) and 'Luebecker Bunte' (Mzmp = 49) ranking first in each species. The complete end-to-end analysis of all 588,070 apple pairwise comparisons took 7.24 s on an ordinary workstation. This deterministic pre-screening framework, with a parameter-free core, supports routine quality assessment in germplasm collections.

genetics↗

bioRxiv2026

Epitope-Focused Immunogens Confer Broad Protection against Coronaviruses

Variable regions in coronavirus spike dominate antibody responses elicited by infection or conventional vaccination and limit induction of broad neutralization. In contrast, conserved S2 elements, including the stem helix (SH) and fusion peptide proximal region (FPPR), are promising but subdominant targets of protective immunity. Here, we employed computational design to generate de novo epitope-focused immunogens that precisely present the SH and FPPR epitopes. Formulated as combinatorial immunogens, this vaccine elicited consistent serum responses with broad reactivity across known human coronaviruses and induced epitope-specific antibodies with broad neutralizing activity. As a heterologous boost, epitope-focused immunogens protected mice against challenge with phylogenetically distinct coronaviruses, including bat SARS-related RsSHC014-CoV and MERS-CoV, establishing a generalizable strategy for precision immune focusing and advancing universal coronavirus vaccine development.

bioengineering↗

bioRxiv2026

Hidden genetic diversity in 320 nearly-complete East Asian genome assemblies

East Asian populations, representing over 20% of the global population, remain critically underrepresented in human genomic studies, limiting our understanding of population-stratified genetic variation and its implications for health and disease. Here we present the first phase of the Asian Pan-Genome project (APG), comprising 320 nearly complete, fully phased haploid genome assemblies from 160 East Asian individuals. These assemblies achieve unprecedented quality, with an average contig N50 of 144.3 megabase pairs and an average quality value of 64.5. Leveraging these superior assemblies, we reveal previously uncharacterized diversity in human repeatome, including population-stratified patterns in centromere satellites and rDNA arrays. Compared to existing global human genome assemblies, the newly generated genomes supplement 152 million base pairs of novel sequences, 355 gene gains, 18,300 structural variation loci and 26 large euchromatic inversions missing from current human pangenomes. We perform population stratification analyses of structural variations, and further resolve the structural haplotypes of complex genomic regions such as Major Histocompatibility Complex and Survival Motor Neuron loci across global pangenomes, exemplifying tandem-duplicate and inversion-rich complex locus architectures in the human genome, respectively. This resource provides a critical foundation for human genetic studies, especially for East Asian populations, promoting more accurate variant discovery, reducing bias, and ultimately advancing the equity and efficacy of genomic medicine.

genomics↗