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Luo, T.

Publications and source records attributed to Luo, T..

At least 19 recordsLinked to original sources

Prediction transfer does not imply reliability transfer in single-cell foundation models

Single-cell foundation models are increasingly transferred across tissues, diseases, perturbation screens, and experimental platforms. Although substantial effort has focused on prediction transfer, it remains unclear whether a model's assessment of its own reliability transfers similarly across biological contexts. Here we define reliability transfer as the ability to transfer an accurate assessment of when model predictions are likely to be correct or incorrect and investigate its behavior across ten perturbation-prediction systems spanning multiple datasets, models, and evaluation settings. We find that reliability transfer varies substantially across source-target pairs and cannot be inferred from predictive performance alone, indicating that prediction transfer and reliability transfer constitute distinct forms of generalization. Analyses of biological annotations, network connectivity, target exposure, and contextual factors reveal that prediction reliability is associated with both shared and context-dependent signals, with their relative importance differing across systems. To characterize this variability, we introduce reliability-attribution fingerprints, context-level signatures derived from strictly cross-fitted SHAP explanations that summarize how reliability estimators combine biological and contextual information when assigning confidence. Across systems, contexts with similar attribution-magnitude fingerprints tended to transfer reliability more successfully, and fingerprint similarity identified transfer sources achieving higher reliability-transfer performance within the observed candidate set. However, these relationships weakened under stricter cross-family transfer settings, indicating that transferable reliability structure remains partly dependent on shared contextual information. Finally, transferred reliability estimators produced different perturbation rankings despite identical perturbation predictions, illustrating a practical consequence of reliability transfer for downstream prioritization. Together, these results establish reliability transfer as a distinct aspect of foundation-model generalization and introduce reliability-attribution fingerprints as a framework for characterizing transferable reliability structure across biological contexts.

bioinformatics↗

Benchmarking longitudinal local centiles for radiographic knee osteoarthritis prognosis

Cartilage thickness on MRI is a structural biomarker of osteoarthritis (OA), yet anatomical variation and aging can mask early disease, including changes occurring 12-36 months before incident OA. We propose longitudinal local centile maps that use normative growth charts as prior information and integrate a knee's earlier scans to identify cartilage that is thinner or thicker than expected. We built the reference charts from 5,045 scans of 957 persistently radiographically normal knees in the Osteoarthritis Initiative. Under participant-separated nested cross-validation, longitudinal centile profiles achieved higher 12- and 24-month AUCs for predicting incident radiographic OA than regional PCA, radiomics, cross-sectional centile features, and raw-map deep features across most classifiers. These conventional descriptors added little when combined with centile profiles, and cross-sectional centiles added little beyond longitudinal centiles. Deep centile features achieved the best AUCs (0.954 [95% CI 0.931-0.974] at 12 months and 0.969 [0.949-0.985] at 24 months; balanced accuracy 0.917 and 0.931) and outperformed raw-map deep features in all 12 classifiers after correction for multiple comparisons. No representation consistently improved 36-month prediction. Longitudinal centiles transform cartilage thickness maps into reference-based deviation maps: deep longitudinal centile features provide the highest predictive accuracy, while regional longitudinal centile profiles provide interpretable prognosis with the second-highest accuracy.

bioengineering↗

Oncogenic fusions induce an extensive cancer-restricted cryptic proteome in Ewing sarcoma

How tumors generate a cryptic "dark" proteome absent from healthy tissues, and whether it can be reversibly activated, remains unclear. In Ewing sarcoma, all tumors are driven by EWSR1::ETS fusions, making it a tractable model to study dark proteome activation. Integrating matched transcriptomes, translatomes and proteomes from 48 patient tumors with long-read RNA sequencing, single-cell Ribo-seq, proteomics and immunopeptidomics in cell line models, we show that EWSR1::FLI1 acts as a reversible switch recurrently inducing hundreds of cancer-specific neoproteins. Many arise from canonical coding regions via intragenic transcription start sites, generating truncated or out-of-frame neoproteins. We uncover a fusion-dependent increase in ribosomal readthrough into poly(A) tails, generating a stable 80-amino-acid TRPM4 neoprotein that, despite lacking a stop codon, is the most abundant tumor-specific microprotein across patients. Proteomic, immunopeptidomic, and immunofluorescence analyses validate neoproteins as tumor-restricted antigens, revealing a therapeutically actionable cancer dark proteome controlled by one oncogenic fusion.

cancer biology↗

Telomeric G-Quadruplexes Formed by Six G-overhang Permutation Repeats

The single-stranded G-overhangs of vertebrate telomeres, composed of guanine (G)-rich hexanucleotide repeats, can adopt six register-dependent permutations: GGTTAG, GTTAGG, TTAGGG, TAGGGT, AGGGTA, and GGGTTA. Telomeric G-quadruplexes (G4s) formed by the first two repeat permutations, which are the most prevalent at human chromosome ends, have been largely overlooked. Here, G4 formation across all six permutations, each containing 4 to 9 repeats, are systematically investigated under varying cation conditions and molecular crowding environments. Our findings reveal that distinct repeat permutations yield markedly different G4 stabilities and folding topologies, which in turn modulate DNA polymerase activity. This expanded perspective on telomeric structural diversity provides new insights into telomere biology and suggests that multiple repeat patterns may cooperatively influence chromosome end protection and targeting.

biophysics↗

Discovery of ARQ-501 as a potent PafA inhibitor that elevates KatG levels to potentiate isoniazid in mycobacteria

The prokaryotic ubiquitin-like protein (Pup) conjugation system (PPS), which is essential for Mycobacterium tuberculosis (Mtb) virulence but absent in humans, presents an attractive drug target. Here, we report the discovery of ARQ-501, a quinone-based, covalent, substrate-competitive inhibitor of the Pup ligase PafA. ARQ-501 exhibited potent anti-mycobacterial activity against Mtb under host-mimicking stress conditions and within macrophages. We further identified the catalase-peroxidase KatG, essential for activation of the frontline prodrug isoniazid (INH), as a pupylation substrate. ARQ-501 inhibits KatG pupylation, causing its accumulation and creating a selective synergy with INH. This quantity over quality mechanism successfully rescued INH activation by the clinically prevalent KatG S315T mutant in enzymatic assays and enhanced INH efficacy against clinical S315T isolates to variable degrees. This work identifies a novel class of PafA inhibitors and a previously unrecognized role of pupylation in regulating KatG, offering a potential therapeutic avenue to combat drug-resistant tuberculosis.

microbiology↗

The Structural Code of Breast Cancer Proteoform: Alternative Splicing-driven Protein Isoform Variation and Functional Diversification

Alternative splicing generates extensive transcript diversity, but the extent to which this diversity contributes to the translated proteome and reshapes protein function remains unclear. Here, we develop 3DisoGalaxy, an atlas integrating transcript reconstruction, ribosome profiling, structural modelling and regulatory annotation in breast cancer. We find that 58,292 of 90,929 transcripts are linked to translation-supported ORFs, 71.9% of which arise from non-canonical transcript structures. These products are broadly accommodated within established protein fold space, indicating that alternative isoforms frequently preserve recognizable protein architectures despite substantial sequence variation. Functional divergence is instead concentrated in domains, intrinsically disordered regions, localization determinants and regulatory motifs. Motif remodelling is biased towards gains and is more extensive in cancer-driver genes than in other genes, linking isoform-associated regulatory variation to cancer-relevant proteins. As an example of domain remodelling, we identify an AKT1-{Delta}PH isoform that lacks the N-terminal PH domain while retaining the kinase core, with immunoblotting revealing a lower-molecular-weight AKT1 species consistent with this isoform. Together, our results show that alternative transcript diversity extensively enters translation-supported proteoform space and establish a systematic link between transcript variation and protein functional diversification.

cancer biology↗

An Isoform-Centric, Structure-Aware Framework for Protein Function Prediction and Evaluation, Instantiated in 3DisoDeepPF

Understanding and accurately predicting function across protein isoforms has been a long-standing challenge with profound implications for both biological and translational research. However, most functional annotations and benchmarks remain tied to genes or reference protein sequences, leaving limited support for distinguishing protein isoforms from the same gene whose sequence, structure and domain composition may lead to different functions. To address this gap, we developed an isoform-centric framework for protein function and domain annotation that integrates a dense graph of sequence and structure similarity with protein features. We implemented this framework as 3DisoDeepPF, a graph-based multimodal model, and applied it to a breast cancer isoform atlas. Across canonical benchmarks and evaluations at isoform resolution, 3DisoDeepPF showed strong performance in predicting GO terms and Pfam domains and remained robust in tests with homology control. It further captured changes in Pfam domain composition among isoforms from the same gene, including reference-relative domain gain and loss. An evidence tracing module links predicted labels to supporting proteins in the graph, as illustrated by the calcium and integrin binding protein 1 (CIB1). Together, this study provides a framework informed by protein structure for function and domain annotation at isoform resolution, converting human protein isoform diversity into traceable functional evidence for cancer atlas interpretation.

cancer biology↗

Connectome-based spatial statistics enabling large-scale population analyses of human connectome across cohorts

Large-scale population analyses of structural connectome organization remain challenging because of cross-subject alignment, pathway interpretability and computational burden. No widely adopted standard exists for systematic evaluation across processing methods. We developed connectome-based spatial statistics (CBSS), a scalable framework for anatomically aligned and functionally informed quantification of white-matter microstructure that yields atlas-defined pathways organized into 13 functional networks. Using data from 56,510 UK Biobank participants together with five independent lifespan cohorts, we evaluated the streamline-, voxel- and network-level measures in the aspects of reliability, heritability, structure-function coupling, cognitive and behavioral prediction, brain aging patterns and lifespan trajectories across cohorts. The systematic evaluation workflow compares population-level white-matter representations across methods, spatial scales, tasks and datasets. The results support CBSS as a common connectome reference for large-scale, cross-cohort diffusion MRI studies.

neuroscience↗

Single-cell Analysis of Paired FFPE Placentas Reveals Trophoblast Reprogramming and Immune Dysregulation in Chronic Villitis of Unknown Etiology

Villitis of unknown etiology (VUE) is a common placental inflammatory lesion associated with adverse pregnancy outcomes, yet its mechanisms remain unclear. Mechanistic studies are hindered by reliance on archived formalin-fixed paraffin-embedded (FFPE) tissues, which are incompatible with standard single-cell methods. Here, we develop an FFPE-compatible single-nucleus RNA sequencing strategy and apply it to paired placentas from sequential pregnancies. VUE placentas exhibit pronounced immune expansion and disrupted trophoblast differentiation. A distinct extravillous trophoblast population and a subset of syncytiotrophoblasts aberrantly express classical MHC class I molecules, promoting natural killer cell engagement and indicating loss of trophoblast immune privilege. Pro-inflammatory maternal macrophages infiltrate, while fetal Hofbauer cells are reduced and transcriptionally reprogrammed. Increased intracellular viral burden and JAK-STAT signaling correlate with aberrant MHC class I expression, suggesting stress-induced local alloimmune activation. These findings define a cellular basis for disrupted maternal-fetal immune tolerance in VUE and demonstrate the utility of FFPE-based single-cell transcriptomics in placental disease.

cell biology↗

Designing smart spatial omics experiments with S2Omics

Spatial omics technologies have transformed biomedical research by enabling high-resolution molecular profiling while preserving the native tissue architecture. These advances provide unprecedented insights into tissue structure and function. However, the high cost and time-intensive nature of spatial omics experiments necessitate careful experimental design, particularly in selecting regions of interest (ROIs) from large tissue sections. Currently, ROI selection is performed manually, which introduces subjectivity, inconsistency, and a lack of reproducibility. Previous studies have shown strong correlations between spatial molecular patterns and histological features, suggesting that readily available and cost-effective histology images can be leveraged to guide spatial omics experiments. Here, we present S2Omics, an end-to-end workflow that automatically selects ROIs from histology images with the goal of maximizing molecular information content in the ROIs. Through comprehensive evaluations across multiple spatial omics platforms and tissue types, we demonstrate that S2Omics enables systematic and reproducible ROI selection and enhances the robustness and impact of downstream biological discovery.

genomics↗

Metabolic response of Brevibacterium epidermidis TRM83610 to NaCl stress and ectoine fermentation optimization

To elucidate the metabolic response of Brevibacterium epidermidis TRM83610 to NaCl stress and facilitate its industrial application, this study employed metabolomics techniques to analyze changes in intracellular metabolites, particularly compatible solutes, under NaCl concentrations of 0, 5%, 10%, and 15%. The ectoine production capacity was further evaluated and optimized using response surface methodology. Results indicated significant metabolic differences among sample groups, with detection of various secondary metabolites associated with antimicrobial activity and plant growth promotion. Six compatible solutes dominated by ectoine were identified. The metabolic response strategies to NaCl stress included osmostress resistance, oxidative stress resistance, and survival competition strategies. Through response surface optimization, ectoine yield reached 440.60 mg/L, representing a 6.22-fold increase over the initial yield of 70.75 mg/L, demonstrating substantial application potential for this strain. This research enriches our understanding of the metabolic profile of B. epidermidis TRM83610, preliminarily reveals its metabolic responses to NaCl stress, and provides a foundational basis for its further development and utilization. IMPORTANCEOur study reports, for the first time, the detection of N{varepsilon}-Acetyl-L-lysine in Brevibacterium epidermidis and the identification of Azetidomonamide A in a microorganism outside of Pseudomonas aeruginosa. It also represents the first elucidation of this strains metabolic response to NaCl stress. This research demonstrates the significant application and research value of B. epidermidis TRM 83610 and reveals that its strategy for coping with NaCl stress is multifaceted. This includes employing multi-pathway synergy to regulate multiple compatible solutes for osmostress resistance, producing antioxidant compounds for oxidative stress resistance, and secreting antimicrobial compounds as part of a survival competition strategy.

microbiology↗

Trpv4 mediates temperature induced sex change in ricefield eel

The ricefield eel (Monopterus albus), an economically important aquaculture species in China, is a freshwater teleost fish that exhibits protogynous hermaphroditism. Although progress has been made in understanding the sex determination and differentiation of this species, the underlying mechanisms remain unclear. Here we show that warm temperature promotes gonadal transformation by up-regulating testicular differentiation genes such as dmrt1/sox9a in ovaries. Trpv4, a Ca2+-permeable cation channel expressed in gonadal somatic cells, is highly sensitive to ambient temperature and links environmental temperature to testicular differentiation in ricefield eel. In female fish reared at cool temperature, injection of Trpv4 agonist into the ovaries leads to a significant up-regulation of male pathway genes, and in female fish exposed to warm temperature, Trpv4 inhibition or trpv4 siRNA knockdown suppresses warm temperature-induced male gene expression. pStat3 signaling is downstream of Trpv4 and transduces Trpv4-controlled calcium signaling into the sex determination cascades. Inhibition of pStat3 activity prevents the up-regulation of testicular differentiation genes by warm temperature treatment and ovarian injection of Trpv4 agonist, whereas activation of pStat3 is sufficient to induce the expression of male genes, in the presence of Trpv4 antagonist. pStat3 binds and activates jmjd3/kdm6b, an activator of the dmrt1 gene. Consistently, ovarian injection of Kdm6b inhibitor blocks the up-regulation of testicular differentiation genes by warm temperature exposure. We propose that environmental factors, such as temperature, promote gonadal transformation of ricefield eel by inducing the expression of male pathway genes in ovaries via the Trpv4-pStat3-Kdm6b-dmrt1 axis. Our results provide new insights into the molecular mechanism underlying natural sex change of ricefield eel, which will be useful for sex control in aquaculture. HighlightsO_LIWarm temperature promotes gonadal transformation of ricefield eel C_LIO_LITrpv4 links environmental temperature and the sex determination pathway C_LIO_LIpStat3 is downstream of Trpv4-controlled calcium signaling C_LIO_LIpStat3 binds and activates kdm6b/jmjd3 C_LI

developmental biology↗

Ultra-high field strength electroporation enables efficient DNA transformation and genome editing in nontuberculous mycobacteria

Efficient DNA delivery is essential for genetic manipulation of mycobacteria and for dissecting their physiology, pathogenesis, and drug resistance. Although electroporation enables transformation efficiencies exceeding 105 CFU per {micro}g DNA in Mycobacterium smegmatis and Mycobacterium tuberculosis, it remains highly inefficient in many non-tuberculous mycobacteria (NTM), including Mycobacterium abscessus. Here, we discovered that NTM such as M. abscessus exhibit exceptional tolerance to ultra-high electric field strengths, and that hypertonic preconditioning partially protects cells from electroporation-induced damage. Using ultra-high electric field strength (3kV/mm) electroporation, we achieved dramatic improvements in plasmid transformation efficiency--up to 106-fold in M. abscessus, 83-fold in Mycobacterium marinum, and 24-fold in Mycobacterium kansasii--compared to standard conditions (1.25 kV/ mm). Transformation efficiency was further influenced by the choice of selectable marker. Ultra-high field strength electroporation also markedly enhanced allelic exchange in M. abscessus expressing Che9c RecET recombinases, increasing recovery of gene deletion mutants by over 1,000-fold relative to conventional electroporation. In parallel, oligonucleotide-mediated recombineering for targeted point mutations produced nearly 10,000-fold more mutants under ultra-high field conditions. Together, these findings establish ultra-high field electroporation as a robust, broadly applicable platform for genetic engineering of NTMs. This method substantially enhances transformation efficiency and enables construction of advanced genetic tools--including expression libraries and CRISPRi knockdown libraries--in species that have historically resisted genetic manipulation. ImportanceInfections caused by non-tuberculous mycobacteria (NTM), including Mycobacterium abscessus, are increasing globally, yet genetic manipulation of these pathogens remains technically challenging due to inefficient DNA delivery and low gene editing success. The ultra-high electric field strength electroporation strategy described here overcomes these barriers, enabling dramatic improvements in both transformation and genome editing efficiency. This advance paves the way for high-throughput functional genomics in NTMs, including the construction of genome-wide knockout, CRISPRi knockdown, and expression libraries. Broad adoption of this approach will accelerate discovery of genetic determinants of virulence and drug resistance, facilitating the development of antimicrobials and vaccines.

microbiology↗

Distinct Connectivity Signatures of Emotions Enhance Precision of Network Biomarkers in Mood Disorders

Mood disorders, including Major Depressive (MDD) and Bipolar (BD) Disorder, are highly prevalent and debilitating conditions that contribute significantly to the global disease burden. These disorders are characterized by persistent emotional dysregulations, such as pervasive sadness and anhedonia, resulting in substantial functional impairments. Although neuroimaging studies have identified differences in brain activity and connectivity between individuals with MDD (MDDs) or BD (BDs) and healthy controls (HCs), reliable and reproducible neurofunctional markers for clinical diagnosis and treatment remain elusive. This study seeks to address this gap by introducing a novel approach that utilizes Divergent Emotional Functional Networks (DEFN), derived from functional magnetic resonance imaging (fMRI) during dynamic emotional processing in naturalistic contexts. Using a combination of naturalistic induction of sustained emotional experience with dynamic functional connectivity (dFC) and machine learning techniques, we decoded emotion-specific patterns of happiness and sadness in healthy individuals. Based on the dynamic functional connectivity signatures, we identify the DEFN and applied it to large clinical mood disorder datasets, including MDD (n=63) and BD patients (n=61). The model with DEFN demonstrated significant improvements in classification accuracy compared to conventional baseline models, achieving up to 10.75% and 9.92% performance increases in MDD and BD datasets, respectively. Additionally, DEFN were found to be highly reproducible across age, gender and models from emotion dataset, supporting the robustness of this model in distinguishing mood disorders from healthy controls. In conclusion, the DEFN approach presents a promising, reproducible, and clinically relevant neural marker for diagnosing and understanding emotional dysfunction in mood disorders, offering potential for more effective and timely interventions.

neuroscience↗

BMP4 is sufficient to induce a caudal organizer

The caudal part of a vertebrate embryo consists of somites, neural tube, lateral plate mesoderm derivatives and the tailbud. However, the minimal conditions and factors sufficient to induce the caudal region, particularly in humans, remain unresolved. Here, we show that BMP4 alone, when administered at appropriate dosage, is sufficient to induce the formation of an organizer for caudal induction. This organizer induces caudal cell fate specification and morphogenesis in zebrafish embryos. In 3D human pluripotent stem cells (hPSCs) aggregates, BMP4 can induce an elongated embryonic structure characterized by caudal fates. Importantly, hPSCs instructed by BMP4 are sufficient to induce a secondary caudal region when grafted into the animal pole of the zebrafish embryo. Our study thus uncovers BMP4 as the inducer in the formation of a caudal organizer in the vertebrate embryo. Significance statementWe demonstrate that BMP4 alone can induce the formation of a caudal organizer, a critical structure that guides the development of the caudal region in vertebrates. Using zebrafish embryos, embryonic explants, human pluripotent stem cell xenografts, and 3D human stem cell aggregates, we show that this organizer replicates morphogenesis and key differentiation pathways seen in natural development. Our findings uncover a novel role for BMP4 and define the minimal requirements for inducing this organizer, offering new insights into vertebrate development and potential applications in regenerative medicine.

developmental biology↗

Thermal Proteome Profiling reveals rapid proteomic responses to redox changes in specific cellular compartments

Hydrogen peroxide (H2O2) functions as a secondary messenger in cellular redox signaling, acting mainly via oxidation of protein thiols. Its spatially and temporally regulated activity within cells is essential for maintaining proper redox balance, and disruptions in these patterns can lead to oxidative stress and various related pathologies. Redox proteomics, which examines the impact of H2O2 at the proteome level, typically focuses only on thiol oxidation, overlooking broader proteomic alterations and the significance of subcellular localization in these redox processes. In this study, we address these open questions by combining chemogenetics with Thermal Proteome Profiling (TPP) to map global proteome response to compartmentalized H2O2 production. We identified hundreds of proteins with altered thermostability and/or abundance upon localized H2O2 generation in the cytosol, nucleus, and the ER lumen, highlighting their roles in cellular responses to localized H2O2. We identified proteins such as MAP2K1, PARK7, TRAP1, and UBA2 to be highly sensitive to localized H2O2 production. Furthermore, we validated their altered thermostability and found that these changes are controlled via dysregulated protein-protein interactions. This study provides a valuable resource for researchers exploring redox-mediated signal transduction and offers novel insights that could be harnessed in treating oxidative stress-induced pathologies.

systems biology↗

SegFinder: an automated tool for identifying RNA virus genome segments through co-occurrence in multiple sequenced samples

Metagenomic sequencing has expanded the RNA virosphere, but many identified viral genomes remain incomplete, especially for segmented viruses. Traditional methods relying on sequence homology struggle to identify highly divergent segments and group them confidently within a single virus species. To address this, we developed a new bioinformatic tool - SegFinder - that identifies virus genome segments based on their common co-occurrence at similar abundance within segmented viruses. SegFinder successfully re-discovered all segments from a test data set of individual mosquito transcriptomes, which was also used to establish parameter thresholds for reliable segment identification. Using these optimal parameters, we applied SegFinder to 858 libraries from eight metagenomic sequencing projects, including vertebrates, invertebrates, plants, and environmental samples. Furthermore, we identified 108 (excluding RdRP) unique viral genome segments, of which 55 were novel and 32 showed no recognizable sequence homology to known sequences but which were verified by the presence of conserved sequences at the genome termini. SegFinder is also able to identify segmented genome structures in viruses previously considered to be predominantly unsegmented, and in doing so expanded the number of known families and orders of segmented RNA viruses, making it a valuable tool in an era of large-scale parallel sequencing.

bioinformatics↗

MAST-Decon: Smooth Cell-type Deconvolution Method for Spatial Transcriptomics Data

AO_SCPLOWBSTRACTC_SCPLOWSpatial transcriptomics (ST) technologies have gained increasing popularity due to their ability to provide positional context of gene expressions in a tissue. One major limitation of current commercially available ST methods such as the 10X Genomics Visium platform is the lack of single cell resolution. Cell type deconvolution for ST data is critical in order to fully reveal underlying biological mechanisms. Existing ST data deconvolution methods share two common limitations: first, few of them utilize spatial neighborhood information. Existing methods such as RCTD and SPOTlight intrinsically treat each spatial spot as independent of neighboring spots, although we anticipate nearby spots to share similar cell type compositions based on clinical evidence of tissue structures. Such limitation could be amplified when sequencing depths at single spots are relatively low so that borrowing information from neighboring spots is necessary in order to obtain reliable deconvolution results. Second, although Visium data provide us with a histological image which could add additional information regarding spot heterogeneity, most existing methods do not utilize this H&E image. To solve these two limitations, we developed Multiscale Adaptive ST Deconvolution (MAST-Decon), a smooth deconvolution method for ST data. MAST-Decon uses a weighted likelihood approach and incorporates both gene expression data, spatial neighborhood information and H&E image features by constructing different kernel functions to obtain a smooth deconvolution result. We showcased the strength of MAST-Decon through simulations based on real data, including a single-cell dataset of mouse brain primary visual cortex, and real-world Visium datasets to demonstrate its robust and superior performance compared with other state-of-the-art methods.

genomics↗