Biology subjects

Xu, X.

Publications and source records attributed to Xu, X..

At least 127 records · Page 7Linked to original sources

bioRxiv2025

Genome assembly and population genomic analysis of Aegilops caudata uncover a rich source for disease and insect pest resistance for wheat improvement

Aegilops caudata L. is a rich source of resistance genes to major wheat pathogens and pests, yet its complex genome structure and lack of a reference sequence have hindered genetic analysis, gene discovery, and introgression. Here, we report a high-quality genome sequence assembly of Ae. caudata accession S740-69, integrated with optical mapping to precisely delineate introgressed segments from structurally altered genomic regions in wheat-Ae. caudata translocation lines carrying a novel stem rust resistance gene. Resequencing and phenotyping of 95 diverse accessions, coupled with k-mer-based association mapping, enabled population-level identification of several novel loci for resistance to wheat pests and diseases, such as greenbug and stem rust. Virus-induced gene silencing confirmed Aecau6C01G127270 (SrAect1) as the first functionally characterized stem rust resistance gene from Ae. caudata. This new genomic framework provides a foundation for systematic mining of resistance genes in this species and their efficient introgression into wheat.

genomics↗

bioRxiv2025

Ultrahigh-Throughput Forster Resonance Energy Transfer-Activated Droplet Sorting for Terminator Polymerase Engineering

Droplet microfluidic screening systems enable high-throughput, labor-saving enzyme directed evolution by employing fluorescence, absorbance, and Raman-activated sorting strategies for library screening. Forster resonance energy transfer (FRET) - a nanoscale technique for monitoring intramolecular/intermolecular conformational changes - is yet to be integrated into this process. We upgraded a single-channel sorter to a dual-channel one without redesigning the microscopy setup, which can monitor FRET signals during enzyme reactions in droplets at kilohertz rates. We applied this upgraded sorter to improve the incorporation efficiency of KOD DNA polymerase towards reversible terminator deoxyribonucleotides, a property crucial for its application in next-generation sequencing (NGS). Our data show that a single-round sorting can achieve 30-fold enrichment of active variants. Five KOD variants enabling 100-cycle single-end runs of DNA sequencing were identified using a novel cyclic reversible termination (CRT) substrate featuring a terminator group {approx} 5-fold bulkier than the classical azidomethyl moiety. We also engineered a metagenome-derived novel polymerase, and a variant achieving 90% terminator incorporation efficiency within 2 minutes was identified after two rounds of enrichment. In sum, we provide a practical setup for dual-channel FRET-based droplet sorting, and demonstrate its ability in terminator polymerases engineering, thereby broaden the scope of microfluidic applications.

biochemistry↗

bioRxiv2025

Cellular interactions in the sentinel lymph node predict melanoma recurrence

Melanoma outcomes have dramatically improved over the past decade, but some patients still experience disease recurrence, particularly those who present at later stage of disease. Prior studies identified an altered immune microenvironment in the sentinel lymph node (SLN) including the presence of dysfunctional CD8 T cells and CD4 T regulatory cells (Tregs), but the spatial organization of the SLN and the interactions of individual cell types have not been extensively studied. To understand how spatial organization of immune cells in the SLN is related to outcomes, we performed spatial proteomic profiling of Stage I and II melanoma SLN to generate an atlas of cell types. Following multiplexed immunofluorescence imaging, deep learning-based segmentation and clustering, we identified 33 subsets of T cells, B cells and Tumor cells. Lymphoid region analyses established a foundational spatial map of the melanoma SLN, revealing higher regional frequencies of activated and memory CD4 T cells in Stage I SLN and consistent positioning of T cells at functional spatial locations. To better understand cellular interactions, we evaluated the immediate neighbors around each index cell using Effect Size Interaction mapping (ESI-map), a novel computational toolkit for understanding spatial interactions. Nearest-neighbor analyses across biological replicates revealed rewiring in cell-cell interacting pairs across disease progression and patient outcomes, particularly with respect to exhausted TOX+ CD8 T cells. Stage II patients who experienced disease recurrence had notable enrichment of cellular interactions between Tregs and TOX+ CD8 T cells that was associated with reduced expression of granzyme B and interferon-{gamma} that was most pronounced in exhausted CD8 T cells. Together, these data demonstrate that the specific spatial interactions between Tregs and exhausted CD8 T cells in the SLN provide a novel immune signature for understanding melanoma outcomes. One Line SummaryTreg-CD8 T cell interactions in the sentinel lymph node predict recurrence outcomes in Stage II SLN+ melanoma patients.

immunology↗

bioRxiv2025

Thalamic Interictal Epileptic and Non-Epileptic Events during NREM Sleep in Patients with Focal Epilepsy: a Stereo-EEG Study

BackgroundThalamic recordings are increasingly incorporated into stereo-electroencephalography (SEEG) evaluations of drug-resistant focal epilepsy to guide neuromodulation targeting. Human thalamic electrophysiology, however, is poorly defined, limiting the distinction between pathological and physiological activity. Here, we characterized interictal epileptic and non-epileptic events during non-rapid eye movement (NREM) sleep across multiple thalamic nuclei and examined their relationship to seizure outcomes. MethodsWe analyzed NREM sleep SEEG recordings from 64 patients with drug-resistant focal epilepsy. Electrodes sampled four thalamic nuclei: centromedian (CM), pulvinar (Pu), ventral lateral (VL), and ventral posterolateral (VPL). Patients were classified into three outcome groups: favorable, unfavorable, and surgically non-remediable. Rates of thalamic spikes, high-frequency oscillations (HFOs), spike-fast activity, and sleep spindles were analyzed and compared across nuclei and outcomes. FindingsRecordings of the thalamus revealed both pathological and physiological interictal events. Interictal epileptic events were infrequent. Only [~]0.2% of seizure-onset zone spikes propagated to the thalamus. Thalamic spike-fast activity was indicative of unfavorable surgical outcomes (CM: p = 0.047, d = 0.46) or surgically non-remediable epilepsy (VL: p = 0.002, d = 0.84). In contrast, thalamic sleep spindles were ubiquitous but reduced in surgically non-remediable patients (CM: p = 0.031, d = -0.58; VL: p = 0.005, d = -0.79). Finally, unique thalamic SEEG patterns were identified, including spikes concomitant with spindles, isolated spikes, and physiological fast ripples. InterpretationThis study provides a comprehensive characterization of thalamic interictal events during NREM sleep, enriching our understanding of thalamic pathophysiology and highlighting the value of thalamic recordings in presurgical evaluation.

neuroscience↗

bioRxiv2025

Genetic architecture and evolution of stripe rust resistance uncovered using diverse panels of wheat lines and North American Puccinia striiformis f. sp. tritici isolates

Newly emerging highly virulent races of Puccinia striiformis f. sp. tritici (Pst) often defeat deployed resistance genes (Yr), highlighting the need for novel sources of durable resistance. A global diversity panel of 377 spring wheat (Triticum aestivum L.) lines was screened for all-stage resistance (ASR) against 20 diverse Pst isolates at the seedling stage and adult plant resistance (APR) against natural mix of field races. Genome-wide association mapping identified 77 unique Yr loci. Of these, 33 overlapped with the previously reported ~1,100 loci, while 44 were likely novel. Nine mapped Yr loci were effective at the adult plant stage and showed no overlap with the known APR genes. Two wheat lines, though lacked the widely effective Yr5 and Yr15 genes, exhibited resistance to all 20 Pst races at the seedling stage and natural field races at the adult stage, suggesting that they may carry novel, broad-spectrum resistance alleles. APR genes Yr18, Yr29, and Yr36 were detected at low frequencies, indicating that much of the observed resistance may arise from less characterized or novel sources. Wheat improvement had no effect on the frequency of ASR alleles but resulted in a three-fold increase in the frequency of APR alleles, suggesting that the latter were subjected to more consistent breeding selection over time. Our findings underscore the value of combined screening of diverse germplasm with the diverse panels of pathogen races to identify novel sources of broad-spectrum resistance for breeding stripe rust resistant cultivars.

genetics↗

bioRxiv2025

DeepRank-Ab: a dedicated scoring function for antibody-antigen complexes based on geometric deep learning

Gaining structural insights into the interactions between antibodies and their corresponding antigens is essential for understanding immune recognition and for guiding therapeutic antibody design. However, accurately modelling these complexes remains a significant challenge for both physics-based docking approaches and AI-based, co-folding methods such as AlphaFold3. These methods not only struggle to generate near native conformations, but, more critically, they often fail to score and rank such conformations correctly, revealing fundamental limitations when applied to antibody-antigen systems. To address these limitations, we present here DeepRank-Ab, a geometric deep learning-based scoring function tailored to the unique characteristics of antibody-antigen interfaces. Its development was enabled by a rigorously curated benchmark comprising more than 2.3 million decoys generated from 1,442 complexes, providing the diversity required for robust training and unbiased evaluation. Leveraging this resource, we systematically assessed multiple levels of graph representation, structural and energetic feature sets, and sampling strategies. Building on our previous DeepRank-GNN-esm work, our analysis identified that atom-level graph representation coupled with Voronoi-based surface decomposition and antibody-specific features is the most effective formulation for accurate scoring. Across multiple independent test sets, including models from unbound unbound docking and structures generated by AlphaFold, DeepRank-Ab consistently outperforms all evaluated methods, including AF3, HADDOCK and state of the art scoring functions such as FTDMP. It increases the AF3 Top 1 success rate by 35.5% and improves the mean Top 1 DockQ by more than a factor of two. DeepRank-Ab further generalizes robustly beyond its training distribution, achieving 100% Top 5 success rate on external antibody-antigen CAPRI targets, surpassing all tested methods. Together, these results demonstrate that DeepRank-Ab is a highly effective scoring method that substantially improves the identification of near-native antibody-antigen conformations.

bioinformatics↗

bioRxiv2025

Gut microbial interaction networks control autoimmunity to neuroretina

The gut microbiome influences the development of immune-mediated inflammatory diseases, including autoimmune uveitis, a sight-threatening ocular inflammation driven by retina-specific T cells1. Using a model of spontaneous autoimmune uveitis (sEAU) we showed that gut commensals provide immune stimuli that trigger disease2. Here we report that uveitis-promoting microbes are present in human gut flora and that colonization of germ-free (GF) mice with commensals from healthy human donors was sufficient to provoke disease. Severity of sEAU correlated with expansion of Akkermansia and contraction of short-chain fatty acid (SCFA)-producing Firmicutes, followed by decreased SCFA levels and a dominant gut Th1 effector response. Mechanistic gain-of-function experiments, enriching GF sEAU mice with Akkermansia, reproduced these microbiome, metabolite and immune phenotype shifts, and exacerbated disease, suggesting that Akkermansia promotes autoimmunity by outcompeting SCFA-producers and enhancing Th1-type responses. An inverse correlation between Akkermansia (Verrucomicrobia) and Firmicutes was also present in patients with uveitis, multiple sclerosis and Crohns disease. These findings reveal a stereotypic gut microbial interaction network that regulates systemic immune balance, and may represent an ecologically conserved mechanism through which the gut microbiome modulates autoimmune and inflammatory diseases.

immunology↗

bioRxiv2025

Multiscale Spatial Transcriptomic Atlas of Human Basal Ganglia Cell-Type and Cellular Community Organization

We generated a multi-region, subcellular-resolution spatial transcriptomic atlas of the human basal ganglia by integrating MERFISH+ and Stereo-seq across four neurotypical donors. These datasets profiled [~]7 million cells spanning the caudate, putamen, nucleus accumbens, and globus pallidus, resolving 60 transcriptionally distinct cell types. We show region-selective, molecular and spatial diversification of medium-spiny-neuron cell types and multiple non-neuronal populations with distinct molecular identities and spatial localizations. Subcellular RNA localization captures somatic size and projection-inferred signatures that reflect direct and indirect pathway topology. Cellular community analyses reveal the enrichment of sub-clusters of astrocytes and oligodendrocytes at striosome-matrix borders, while primate-expanded interneurons are confined to matrix territories. Cross-species mapping uncovers orthologous striosome-matrix organization and conserved dorsolateral-ventromedial gene expression gradients. This atlas provides a foundational molecular and spatial framework for studying human basal ganglia architecture, offering a multi-centimeter scale resource that links cell types, spatial architecture, and subcellular transcript topography across multiple nuclei. HighlightsO_LIOur multi-centimeter scale spatial taxonomy identifies the precise locations of 60 neuronal and glial cell types of human basal ganglia. C_LIO_LIMERFISH+ and Stereo-seq platforms map consistent spatial modules that align with classical neuroanatomical nuclei. C_LIO_LID1D2 hybrid MSNs and primate-expanded interneurons show regional and domain specific organization C_LIO_LISubcellular RNA localization reports soma morphology and projection-inferred signatures. C_LI

neuroscience↗

bioRxiv2025

Preserved Neural Dynamics across Arm- and Brain-controlled Movements

The neural activity for motor control is complex and dynamic; it has been found to dramatically transit from planning to executing movements. As brain-machine interfaces (BMIs) can directly connect the brain and the external world by yielding comparable motor outcomes with artificial apparatus, a central question is whether the BMI-controlled movements share neural dynamics or underlying mechanism with natural movements. To enable a systematic comparison, we developed a feedforward BMI framework with distinct planning and executing epochs that enables ballistic cursor control to intercept moving targets. This BMI allowed monkeys to voluntarily initiate neural states which controlled the direction and timing to launch a ballistic movement, like skeet shooting. Based on this, we found similar neural representations and computational structures across arm- and brain-controlled conditions. Notably, in addition to resembling the rotational structure in natural reaching, the neural population dynamics during open-loop BMI also shared preserved manifolds with those during reaching arm movements. These findings suggest a fundamental principle, and reveal a set of basic computational motifs for the neural control of movement in an abstract hierarchy in the absence of constraints from actuators. This study thus has the potential to reshape the consideration of how BMIs assist paralyzed patients in interacting with dynamic environments, and to promote next-generation BMI systems.

neuroscience↗

bioRxiv2025

NanoporeDB: A Structural Resource Of Multimeric Protein Nanopores In Single-Molecule Sensing

Protein nanopores are essential molecular gateways in biology and have inspired transformative technologies in biosensing and single-molecule sequencing. While this technology has transformed genomics and biosensing, the discovery of novel nanopore scaffolds remains limited due to the scarcity of experimentally resolved pore structures. Here, we present NanoporeDB, an open-access structural resource comprising over 6,600 high-confidence multimeric models across four representative pore types. Candidate proteins were systematically mined from large-scale datasets, including the AlphaFold Protein Structure Database, UniRef90, and MGnify90, and assembled using AlphaFold-Multimer and AlphaFold3. We performed membrane embedding, pore axis annotation, and constriction profiling to enable functional interpretation. NanoporeDB features an interactive web interface with 3D visualization and quantitative metrics such as insertion depth, tilt angle, and pore geometry. This resource provides a structural foundation for advancing nanopore-based molecular sensing, precision diagnostics, and synthetic biology.

bioinformatics↗

bioRxiv2025

Single-Cell Multi-Omics Dissects Transcript Isoform and Immune Repertoire Dynamics in Human Immunosenescence

Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations in immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this, we present the human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoforms diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy young and elderly donors. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we identified in CD4 effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes--all closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.

immunology↗

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

Rectal Transplantation of Fragmented Intestinal Organoids and Crypts Promotes Mucosal Regeneration in DSS-Induced Colitis

BackgroundUlcerative colitis (UC) represents a global health challenge characterized by relapsing inflammation and epithelial barrier disruption. Conventional immunosuppressive therapies have reached their therapeutic ceiling, with mucosal healing and long-term remission remaining unmet therapeutic goals for many patients. Organoid-based regenerative therapy offers a new paradigm by reconstructing damaged mucosa rather than merely controlling inflammation. MethodsWe hypothesized that fragmented intestinal organoids, building upon the foundational model established by Yui et al., whose use of immunodeficient Rag2-/- mice and surgical mucosal injury first demonstrated the feasibility of colon organoid transplantation. Our study advances this framework by introducing optimized transplantation timing and employing immunocompetent C57BL/6 mice to refine translational relevance and clinical feasibility, thereby extending the applicability of organoid therapy to more realistic physiological contexts., when transplanted rectally at an optimized time point, could integrate more efficiently into inflamed mucosa and accelerate epithelial regeneration even in an immunocompetent environment. A 2.5% dextran sulfate sodium (DSS)-induced colitis model was established in C57BL/6 mice. Intestinal organoids and crypts derived from EGFP-transgenic donors were cultured and transplanted rectally using a minimally invasive delivery system. Fluorescence microscopy, histological analysis, and clinical indices were used to evaluate engraftment and mucosal repair. ResultsEGFP+ organoid fragments and crypts successfully engrafted at ulcerated sites, reconstituting epithelial structures and restoring mucosal integrity. Mice receiving organoid or crypts transplantation exhibited rapid weight recovery and reduced bleeding compared to DSS-only controls. Histological and fluorescence analyses confirmed epithelial restitution exceeding 60% by day 7 post-administration versus 18% in controls. These results validate the regenerative potential of organoid transplantation within an immunocompetent host. ConclusionThis study demonstrates that rectal transplantation of fragmented intestinal organoids and crypts promotes robust mucosal regeneration in DSS-induced colitis. By optimizing transplantation timing and employing a clinically relevant model, our work establishes a translational foundation for organoid-based regenerative therapies targeting inflammatory bowel diseases.

bioengineering↗

bioRxiv2025

Multimodal AI Decodes Extreme Environment Functional Dark Matter Beyond Homology

Functional annotation of proteins from extreme environments represents a major bottleneck for bioresource discovery, as a vast reservoir of functional dark matter defies existing homology-based methods. We demonstrate that environmental pressures impart conserved physicochemical energy signatures that co-determine protein function with sequence and structure. Here we developed ACCESS, a multimodal graph neural network employing hierarchical contrastive learning with a tailored label-sample co-embedding to fuse energy, sequence, and structural information and overcome homology scarcity. ACCESS surpasses state-of-the-art methods including BLASTp and CLEAN in annotating low-identity enzymes. Applied to extreme environmental metagenomics, we constructed a function map of extremophile enzymes to expand the biocatalyst library, pinpointed functionally critical residues to guide rational design, and enabled large-scale, function-based macro-evolutionary analyses. This paradigm transcends the limitations of homology, illuminating protein dark matter and accelerating the exploration of the biospheres functional diversity for applications in biotechnology and therapeutic development.

bioinformatics↗

bioRxiv2025

Blood originates in hypoblasts during embryonic development

Blood is essential for oxygen supply throughout life. The emergence of blood in the human embryo remains poorly understood. Our study leverages multiple stem cell embryo models and advanced lineage barcoding to unveil that hypoblast, originally regarded as forming the yolk sac wall, is heterogeneous and contributes to CDX2+ extraembryonic mesoderm, followed by hemoglobin+ cells as the first blood cells. CDX2 marks the hypoblast-to-hemoglobin+ cell trajectory that functionally sustains oxygen levels in embryo models. These hemoglobin+ cells molecularly and functionally resemble phagocytes. We show that the erythro-core regulatory network is poised in hypoblasts, and its boost endows erythropoiesis to both hypoblasts and phagocytes. Hypoblasts are the origin of the first blood in humans and non-human primates, providing a conceptual framework that earlier blood generation than expected fills the gap in the establishment of circulation. Further, the hypoblast is a place where primates may repurpose the phagocyte program to carry oxygen throughout embryos. HighlightsO_LIBarcode-traced hypoblast fate in human embryo models; C_LIO_LIThe first blood comes from the hypoblast that contributes to hemoglobin+ phagocyte-like cells; C_LIO_LICDX2 marks hypoblast blood that sustains oxygen supply in embryos before heart formation; C_LIO_LIErythro-core regulatory network endows erythropoiesis to human hypoblasts and phagocytes. C_LI

developmental biology↗

bioRxiv2025

CARP Protects Against Doxorubicin-induced Cardiotoxicity through NRF1-driven Mitochondrial Homeostasis

AimsDoxorubicin (DOX), a highly effective anthracycline chemotherapeutic agent, is limited by its dose-dependent cardiotoxicity. This study investigates the cardioprotective mechanisms of cardiac adriamycin responsive protein (CARP) and its underlying mechanisms in DOX-induced cardiotoxicity (DIC). Methods and resultsCardiac-specific CARP transgenic and wild-type mice were subjected to a DIC model. Cardiac function was assessed via echocardiography, histopathology, and transmission electron microscopy (TEM). In vitro, DOX-treated cardiomyocytes overexpressing CARP were analyzed for oxidative stress (ROS levels), mitochondrial function (mtDNA copy number etc.), and mitochondrial-related proteins (Western blot). CARP-NRF1 interaction was validated by co-immunoprecipitation (Co-IP), and NRF1 siRNA knockdown was performed to assess CARPs role in mitochondrial homeostasis. CARP overexpression markedly alleviated DOX-induced cardiac dysfunction and mitochondrial damage, restoring mitochondrial dynamics and mitophagy. Mechanistically, CARP directly interacted with NRF1, and NRF1 knockdown ameliorated CARP-mediated cardioprotection in DIC. ConclusionCARP safeguards against DIC by maintaining mitochondrial homeostasis via NRF1 signaling, positioning it as a promising therapeutic target for DOX-induced cardiomyopathy.

molecular biology↗

bioRxiv2025

Deep learning assessment of nativeness and pairing likelihood for antibody and nanobody design with AbNatiV2

1Immune systems create antibodies that balance good binding and stability with low toxicity and self- reactivity. Quantifying the nativeness of a candidate sequence - its likelihood of belonging to natural immune repertoires - has thus emerged as a valuable strategy for hit selection from synthetic libraries, optimisation and humanisation, and for guiding de novo design towards developable candidates. We previously introduced AbNatiV, a transformer-based VQ-VAE for nativeness assessment, which proved effective across multiple nanobody engineering tasks. However, AbNatiV1 operated on unpaired sequences, limiting applicability to conventional VH-VL antibodies. Moreover, its performance on nanobody nativeness was constrained by the limited number and diversity of nanobody repertoires available at the time. Here, we sequenced new camelid repertoires, curated additional recent datasets, and present AbNatiV2: an enhanced architecture comprising various models each trained on [≥] 20 million sequences. AbNatiV2 improves nanobody nativeness classification across held-out and diverse test sets, and more robustly detects nativeness changes upon CDR grafting. We also introduce p-AbNatiV2, a cross-attention model fine-tuned on 3.7 million paired human sequences. p-AbNatiV2 provides residue- and sequence-level humanness for VH/VL pairs and learns pairing-likelihood via noise-contrastive training. On held-out tests, it assigns the native pair a higher score in 74% of cases, substantially outperforming recent pairing models. Together, AbNatiV2 and p-AbNatiV2 extend nativeness assessment and engineering to both nanobodies and conventional antibodies, supporting design decisions at single-residue, Fv-sequence, and paired-domain levels. We make AbNatiV2 available as downloadable software and webserver.

bioengineering↗

bioRxiv2025

Universal super-resolution for subcellular fluorescence imaging

Super-resolution fluorescence microscopy has emerged as an essential instrument for investigating subcellular structures and monitoring intracellular physiology. Despite rapid advances driven by deep learning, most existing approaches are modality specific and exhibit limited generalizability, restricting their practical applicability. Here we introduce universal super-resolution (UniSR), a framework that operates across microscopes and subcellular structures without optical modifications or prior sample knowledge. UniSR is initially pre-trained on simulated image pairs to establish mappings from low-to high-resolution features and subsequently fine-tuned with only one experimental image pair, reducing data demand and acquisition time. Across wide-field and point-scanning modalities, UniSR enhances resolution to match structured illumination, single-molecule localization, or stimulated emission depletion microscopy. Applied to diverse biological samples, it reveals nanoscale structures, dynamic processes, and organelle interactions with high spatiotemporal fidelity. UniSR provides a practical and broadly generalizable tool for super-resolution imaging in live-cell research.

bioinformatics↗