Biology subjects

Oh, J.

Publications and source records attributed to Oh, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

ALTAA: analysis of long-term activity patterns in ant colonies

Collective behaviours are a fascinating study area due to the emergent properties that can only arise in groups of interacting individuals. However, their quantitative study is often impaired by technical difficulties, creating either low-quality and sparse data, or impractical data amounts, particularly when capturing large groups over long periods of time. Common challenges arise from recording group members with as little obscuring of each other as possible, as well as in generating manageable data amounts with as high as possible information content. We here provide a multi-component system that allows to record, analyze and simulate the long-term spatiotemporal activity patterns of insect collectives, especially ant colonies. Our Ant Observing System, ALTAA, comprises a flat nest design to prevent occlusion of individuals, a recording system running on a low-power single-board-computer, and a set of computer programs performing quantitative analyses to guide the formation and validation of rules underlying the observed collective patterns. Our system is scalable in that it allows parallel, continuous observation of a high number of colonies using low memory space, with colony maintenance requirements (e.g. feeding, nest humidity) being achieved at lowest possible disturbance by the experimenter. We showcase the potential of the system in a study using the black garden ant, Lasius niger, where we analyze the spatiotemporal effects of different group size (1, 6, 10 ants), brood (larvae) presence or absence, as well as of different nest geometries, over a period of one week. We show that the ants motion activity has a weak periodicity in the range of 20 to 120 minutes promoted by larval presence, and that ants are spatially attracted to their larvae, the water source and the walls. We also find that the presence of nestmates lowers an individual ants motion activity. Observed data are compared to simulations of the temporal activity of the ants. ALTAA provides a powerful toolkit to quantify and interpret spatial and temporal collective activity patterns in (social) insects over extended periods.

animal behavior and cognition↗

bioRxiv2025

De novo identification of the specificities of recurrent human T cell receptors

T cell repertoires of different individuals occasionally converge on the same T cell receptor (TCR) sequence as a solution to target immunodominant epitopes. A complete mapping of these "public" TCR specificities may enable a global understanding of population-level immune histories. Here, we sought to determine the antigen specificities of public TCRs with unknown target identity. We developed a functional screening workflow in which we screen panels of TCRs for reactivity to individual viral genomes or to approximately 1,000 viral reference strains, and then sort out the immunogenic peptides by labeling antigen-presenting cells that are in proximity to activated T cells. Using this workflow, we identified the target specificities of T cells that are circulating in up to 14% of individuals, including a pre-COVID-19 seasonal coronavirus-reactive TCR that cross-reacts with peptides within pandemic coronaviruses; an influenza B-reactive TCR that targets a highly conserved epitope; and TCRs targeting Herpesviridae family viruses that cause long-term latent infections. Our results demonstrate an efficient strategy to reveal public T cell memories de novo, offering a window into shared immune exposures.

immunology↗

bioRxiv2025

GraphTME: a framework for predicting response to immune checkpoint inhibitors by interpreting cell-cell interactions in the tumour microenvironment using spatial transcriptomics of tumour tissue

Immune checkpoint inhibitors (ICIs) have been used to treat cancer by reactivating T-cell responses against tumours, yet clinical efficacy remains limited due to low response rates and the lack of robust predictive biomarkers. The tumour microenvironment critically shapes ICI responsiveness by modulating antitumour immunity, necessitating a deeper understanding of spatially organised cell-cell interactions. Imaging-based spatial transcriptomics (ST) enables such analysis at single-cell resolution. We present GraphTME, a spatially informed and biologically interpretable framework that models pathway-specific directional cell-cell interactions to predict anti-PD-1 response. Ligand-receptor interactions are organised by signalling pathways and represented as a multi-relational directed graph, with edge weights inversely scaled by spatial distance. Using CD8+ T cells from single-cell RNA-seq data of ICI-treated NSCLC patients, we trained a relational graph convolutional network to infer immune responsiveness. GraphTME achieved an F1 score exceeding 0.83 in predicting ICI response and was validated using MERFISH data from an NSCLC patient with a partial response. Predicted responder CD8+ T cells exhibited higher abundance and stronger directional signalling to tumour cells. They also expressed genes associated with antitumour activity, while non-responders showed expression patterns linked to poor prognosis. GraphTME is the first framework to quantitatively model single-cell-level interactions within the spatial architecture of tumour tissues and predict ICI responses from these interactions. It offers a spatially resolved, biologically grounded biomarker for immunotherapy and a tool for dissecting immune dynamics in situ.

bioinformatics↗

bioRxiv2025

Host-specific bacterial modulation of airway gene expression and alternative splicing

The human microbiome varies extensively between individuals. While there are numerous studies investigating the effects of inter-individual differences on microbiome composition, there are few studies investigating inter-individual effects on microbial modulation of the host, or host-specific effects. To address this knowledge gap, we colonized human bronchial epithelial air-liquid interface tissue cultures generated from six different adults with one of three phylogenetically diverse bacteria and compared how each microbe differentially modulated host gene expression in each of the six donors. Microbial treatment had the strongest effect on transcription, followed by donor-specific effects. Gene pathways differed markedly in their donor- and microbe-specificity; interferon expression was highly donor-dependent while transcription of epithelial barrier and antibacterial innate immunity genes were predominantly microbially driven. Moreover, we evaluated whether microbial regulation of alternative splicing was modulated by donor. Strikingly, we found significant non-redundant, donor-specific regulation of alternative splicing exclusively in the Gram-positive commensal microbes. These findings highlight that microbial effects on the human airway epithelium are not only species-specific but also deeply individualized, scoring the importance of host context in shaping microbe-induced transcriptional and splicing responses.

microbiology↗

bioRxiv2025

Inferring Spatially Varying Bending Stiffness of Biopolymers with Deep-Learning Approach

The bendability of biopolymers, including DNA, actin filaments, and microtubules, is crucial to diverse biological processes, such as cell motility and cytoskeletal organization. While conventional polymer models like the worm-like chain model assume uniform bending stiffness along the contour, biopolymers in reality often attain spatially varying bending stiffness as a result of complex cellular interactions. For instance, the bending stiffness of actin filaments and microtubules varies in response to associated binding proteins or chemical modifications. Despite its biological implications, measuring the position-dependent persistence length along polymer contours remains challenging. Here, we present a deep-learning-based method that quantitatively predicts spatially varying bending stiffness of biopolymers. Our framework segments a polymer chain into short over-lapping fragments, predicts local persistence lengths using a deep-learning model, and reconstructs full profiles. Using simulated data, we demonstrate that our approach achieves high accuracy and robustness even under data-scarce conditions. Applied to various biological systems, our method reveals a spatially varying stiffness from tip to base in filopodia as well as spatially heterogeneous stiffness in microtubules. Additionally, we investigate the internal mechanism of our deep-learning model and show that the model utilizes multiple physics-related features for persistence length estimation while adaptively adjusting its attention based on polymer stiffness.

biophysics↗

bioRxiv2025

A single MHCII neoepitope mRNA vaccine elicits CD4 T- and B- cell responses promoting endogenous CD8 anti-tumor immunity

Recent progress in therapeutic cancer vaccines has shown promising clinical activity, especially when targeting MHC class I (MHCI) neoantigen-specific CD8+ T cell responses in post-surgical patients. To explore the role of CD4+ T cells in vaccine-dependent tumor rejection, we constructed an mRNA lipoplex vaccine encoding a single MHCII-restricted neoantigen. The vaccine elicited Tfh and Th1 cell responses while decreasing Tregs, leading to rejection of established tumors in mice. IL-21 and IFN-{gamma}, crucial for Tfh and Th1 function respectively, contributed to anti-tumor activity. B cells and neoantigen-specific antibodies were also shown to participate in vaccine efficacy. Additionally, conventional type 1 dendritic cells (cDC1s) were essential for eliciting vaccine-induced CD4+ T cells, and both cDC1s and CD4+ T cells were required to enhance endogenous CD8+ responses, which were crucial for tumor control. Our results suggest that immunizing against MHCII neoantigens alone is sufficient to orchestrate a potent and cooperative immune response against cancer.

immunology↗

bioRxiv2025

Differential DNA damage response to WRN inhibition identifies a targetable vulnerability in ARID1A-mutated cancers

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancers. However, effective clinical treatments for patients with this mutation are limited, highlighting a demand for new therapeutic strategies. Here, we establish Werner syndrome ATP-dependent helicase (WRN) as a critical vulnerability target in ARID1A-mutated cancers. Upon genetic and pharmacological inhibition of WRN, ARID1A-mutated cells had defective Chk1-mediated DNA damage signaling, resulting in compensatory Chk2 activation, leading to G1-phase arrest and apoptosis, whereas ARID1A-proficient cells underwent Chk1-dependent G2/M arrest. Additional p21 inhibition, combined with WRN suppression, drove G1-arrested cells to re-enter the cell cycle, triggering mitotic catastrophe. The anti-tumor efficacy of WRN inhibition was validated using in vivo cell lines and patient-derived xenograft mouse models. Our findings define WRN as a selective therapeutic target in ARID1A-mutated cancers and suggest a combinatorial strategy of WRN and p21 inhibition as a therapeutic approach.

cancer biology↗

bioRxiv2025

Sex Differences in the Cancer Proteome

Proteins play a central role in cancer biology: they are the most common drug targets and biomarkers. Sex influences the proteome in many diseases, ranging from neurological to cardiovascular. In cancer, sex is associated with incidence, progression and therapeutic response, as well as characteristics of the tumour genome and transcriptome. The extent to which sex differences impact the cancer proteome remains largely unknown. To fill this gap, we quantified sex differences across 1,590 proteomes from eight cancer types, identifying 901 genes with sex-differential proteins abundance in adenocarcinomas of the lung, and 20 genes across five other tumour types: squamous cell carcinoma of the lung, hepatocellular carcinomas, clear cell cancers of the kidney, adenocarcinomas of the pancreas and glioblastoma. A subset of these protein differences could be rationalized by sex-differential copy number aberrations. Pathway analysis showed that male-biased proteins in lung adenocarcinoma were enriched in MYC and E2F target pathways. These findings highlight the modest impact of sex on the cancer proteome, but the very limited power of existing proteomics cohorts for these analyses.

cancer biology↗

bioRxiv2025

SoEM-Web: a user-friendly platform for the analysis and visualization of small-organelle-enriched metagenomics data

BackgroundMarine microeukaryotes play a crucial role in global biogeochemical cycles and ecosystem functioning. However, their diversity and distribution patterns remain poorly understood. To improve the biodiversity assessment of environmental samples, we recently developed a PCR-free, small-organelle-enriched metagenomics (SoEM) method, accompanied by a bioinformatics workflow for analyzing SoEM metagenomic data. However, the complexity of these analyses typically requires extensive bioinformatics expertise, potentially limiting their broader adoption. MethodsTo address this challenge, we present SoEM-Web, a user-friendly web application for the interactive analysis, classification, and visualization of SoEM metagenomic data. SoEM-Web integrates all necessary procedures, including raw sequencing data preprocessing, paired-end read merging, automated taxonomic identification, and diversity visualization, into a streamlined workflow accessible through an intuitive interface. This application is designed to facilitate SoEM data analysis for researchers who may not have advanced bioinformatics skills. ResultsWe demonstrated the capabilities of SoEM-Web by reanalyzing previously published datasets. This reanalysis not only confirmed the utility of the platform but also revealed additional taxa, emphasizing the value of updated reference datasets. The application successfully simplifies complex bioinformatics processes, enhancing accessibility and reproducibility in marine microeukaryote diversity research. SoEM-Web aims to enhance accessibility and reproducibility in marine microeukaryote diversity research. The web server is freely available at http://compsysbio.re.kr/soem-web/.

bioinformatics↗

bioRxiv2025

The Landscape of Prostate Tumour Methylation

Prostate cancer is characterized by profound clinical and molecular heterogeneity. While its genomic heterogeneity is well-characterized, its epigenomic heterogeneity remains less understood. We therefore created a compendium of 3,001 multi-ancestry prostate methylomes spanning normal tissue through localized disease of all grades to poly-metastatic disease. A subset of 884 samples had multi-omic DNA and/or RNA characterization. We identify four epigenomic subtypes that risk-stratify patients and reflect distinct evolutionary trajectories. We demonstrate extensive regulatory interplay between DNA copy number and methylation, with transcriptional consequences that vary across genes and disease stages. We define epigenetic dysregulation signatures for 15 important clinico-molecular features, creating predictive models for each. For example, we identify specific epigenetic features that predict patient outcome and are synergistic with clinical prognostic features. These results define a complex interplay between tumour genetics and epigenetics that converges to modify gene-expression programs and clinical presentation, in part through modulation of epigenetic aging.

cancer biology↗

bioRxiv2025

Sex Differences in Cancer Functional Genomics: Gene Dependency and Drug Sensitivity

Patient sex influences a wide range of cancer phenotypes, including prevalence, response to therapy and survival endpoints. Molecular sex differences across the central dogma have been identified that may drive these phenotypic differences. Despite a growing catalog of specific genomic, transcriptomic and proteomic sex differences in a range of cancer types, their functional consequences remain unclear. To assess how patient sex impacts cancer cell function, we evaluated 1,209 cell lines subjected to CRISPR knockout, RNAi knockdown or drug exposures. Despite limited statistical power, we identified pan- and per-cancer sex differences in gene essentiality in six sex-linked and fourteen autosomal genes, and in drug sensitivity for two compounds. These data expand our understanding of the propagation of sex-differing molecular features to functional outcomes, and their role in influencing patient phenotypes. They highlight the importance of considering sex-specific effects in mechanistic and functional studies.

cancer biology↗

bioRxiv2025

Biosynthetic plasticity enables CD8+ T cell functional resilience under nutrient stress

Summary / AbstractTo maintain lineage-specific functions, cells must acquire and allocate nutrients across diverse cellular processes, even in metabolically-dysregulated environments. The mechanisms allowing CD8+ T cells to maintain immune function in perturbed environments are poorly understood. We find that CD8+ T cells adapt to nutrient stresses over time, reconfiguring gene-regulatory and metabolic networks to license functional recovery. Under acute stress, T cells reorient translational programming, limiting nutrient demand while prioritizing stress-sensitive metabolic and transcriptional responses. Within these responses, the transcription factors ATF4 and CEBPG jointly establish an adaptive metabolic program, promoting amino acid synthesis and uptake while maintaining mitochondrial anaplerosis. Despite diminished energetic capacity under environmental stress, this program prevents failure of central carbon metabolism, mitigating stress amplification and cellular dysfunction to potentiate anti-tumor immunity. Altogether, we demonstrate that biosynthetic plasticity via translational and metabolic reprioritization confers functional resilience to immune cells in unfavorable environments, offering novel strategies to enhance immunotherapies.

immunology↗

bioRxiv2024

Adherent-to-suspension transition promotes melanoma metastatic dissemination

Melanoma is a highly metastatic skin cancer that often evades current therapeutic strategies primarily because of the complex mechanisms involved in metastasis. This study investigated the role of adherent-to-suspension transition (AST) in melanoma and its potential to facilitate metastasis by reprogramming cellular anchorage dependency. Using melanoma models, we demonstrated that the AST factors IKZF1, IRF8, and NFE2 are crucial for reprogramming, influencing gene expression related to cell adhesion and survival. Notably, our results highlight that AST factor expression undergoes dynamic changes during metastasis, which can be reversed in circulating tumor cells. Our findings revealed that AST contributes to the increased metastatic potential and invasiveness of melanoma cells and underscores its role independent of the epithelial-to-mesenchymal-like transition pathways. Based on the results, we highlight the potential of targeting AST mechanisms to develop new therapeutic strategies against metastasis.

cancer biology↗

bioRxiv2024

TEAL-seq: Targeted Expression Analysis Sequencing

Metagenome sequencing enables genetic characterization of complex microbial communities. However, determining the activity of isolates within a community presents several challenges including the wide range of organismal and gene expression abundances, the presence of host RNA, and low microbial biomass at many sites. To address these limitations, we developed "targeted expression analysis sequencing" or TEAL-seq, enabling sensitive species-specific analyses of gene expression using highly multiplexed custom probe pools. For proof-of-concept we targeted about 1,700 core and accessory genes of Staphylococcus aureus and S. epidermidis, two key species of the skin microbiome. Two targeting methods were applied to laboratory cultures and human nasal swab specimens. Both methods showed a high degree of specificity, with >90% reads on target, even in the presence of complex microbial or human background DNA/RNA. Targeting using molecular inversion probes demonstrated excellent correlation in inferred expression levels with bulk RNA-seq. Further, we show that a linear pre-amplification step to increase the amount of nucleic acids for analysis yielded consistent and predictable results when applied to complex samples and enabled profiling of expression from as little as 1 ng of total RNA. TEAL-seq is much less expensive than bulk metatranscriptomic profiling, enables detection across a greater dynamic range, and uses a strategy that is readily configurable for determining the transcriptional status of organisms in any microbial community. IMPORTANCEThe gene expression patterns of bacteria in microbial communities reflect their activity and interactions with other community members. Measuring gene expression in complex microbiome contexts is challenging, however, due to the large dynamic range of microbial abundances and transcript levels. Here we describe an approach to assessing gene expression for specific species of interest using highly multiplexed pools of targeting probes. We show that an isothermal amplification step can allow profiling of low biomass samples. TEAL-seq should be widely adaptable to the study of microbial activity in natural environments.

genomics↗

bioRxiv2024

Adherent-suspension plasticity promotes the dissemination and colonization of circulating tumor cells

Cell competition within the primary tumor drives tumor growth by promoting the uncontrolled proliferation of winner cells and eliminating loser cells by sensing cell fitness. However, the mechanism of how cell competition confers the loser cells with the metastatic potential of circulating tumor cells (CTCs) to transit between dissemination and colonization remains elusive. Here we found cell competition gives rise to less fit but viable cells that transformed into CTCs via adherent-to-suspension transition (AST) mechanisms. The induction of hematopoietic transcription factors hijacked by solid tumor cells rendered CTCs competent to reprogram their anchorage dependency and disseminate into the bloodstream, while subsequent suppression of these factors was critical to regain adhesion and colonize metastatic lesions. Disrupting the oscillatory dynamics of AST factors blocked the adherent-suspension plasticity (ASP) of breast cancer CTCs and suppressed lung metastasis. Furthermore, multiregional single-cell transcriptomic analyses of matched primary tumors, CTCs, and metastatic lesions from de novo metastatic breast cancer patients demonstrate the critical role of ASP in metastasis. SignificanceWe demonstrate cell competition-mediated displacement of loser cells manifests dynamic oscillation of AST factors that confer anchorage plasticity to circulating tumor cells critical for their dissemination and colonization in metastasis. These findings highlight the potential of targeting AST factors to develop effective anti-metastatic therapies.

cancer biology↗

bioRxiv2024

Yanomami skin microbiome complexity challenges prevailing concepts of healthy skin.

The adult skin microbiome contributes to skin homeostasis and generally comprises relatively low microbial complexity, especially sebaceous sites, where lipophilic Cutibacterium and Malassezia spp. predominate. Current understanding of the healthy skin microbiome derives predominantly from studies of western, industrialized populations, with limited representation of diverse cultures and lifestyles. In this study, the skin microbiome of a remote indigenous Yanomami community was investigated, revealing a complex microbial community comprised of 115 novel bacterial genomes. The bacterial community composition included genera common to western skin microbiota and additional diverse taxa, which formed multiplex interactions with a dominant eukaryote, Malassezia globosa. Metatranscriptome-derived functional attributes of the microbial communities contributed to skin homeostasis, fortifying barrier integrity via lipid metabolism and acid production and protecting against oxidative stress. The Yanomami skin microbiome comprised a suite of microbial taxa co-detected within their various surroundings. Longitudinal monitoring of Western expeditioner microbiome revealed acquisition of the Yanomami skin microbiome following immersion into the Amazon and subsequent loss upon return to an industrialized setting. These findings challenge the prevailing Western-centric view of what comprises a healthy adult skin microbiome, suggesting a diverse community that includes bacteria of environmental origin confers benefits not recognized in the current model of healthy skin. Importantly, we highlight the malleability of adult skin microbiome composition, which includes changes sustained by lifestyle modification.

microbiology↗

bioRxiv2024

StableLift: Optimized Germline and Somatic Variant Detection Across Genome Builds

Reference genomes are foundational to modern genomics. Our growing understanding of genome structure leads to continual improvements in reference genomes and new genome "builds" with incompatible coordinate systems. We quantified the impact of genome build on germline and somatic variant calling by analyzing tumour-normal whole-genome pairs against the two most widely used human genome builds. The average individual had a build-discordance of 3.8% for germline SNPs, 8.6% for germline SVs, 25.9% for somatic SNVs and 49.6% for somatic SVs. Build-discordant variants are not simply false-positives: 47% were verified by targeted resequencing. Build-discordant variants were associated with specific genomic and technical features in variant- and algorithm-specific patterns. We leveraged these patterns to create StableLift, an algorithm that predicts cross-build stability with AUROCs of 0.934 {+/-} 0.029. These results call for significant caution in cross-build analyses and for use of StableLift as a computationally efficient solution to mitigate inter-build artifacts.

genomics↗

bioRxiv2024

Teicoplanin attenuates RNA virus infection in vitro

Teicoplanin (TP) is a glycopeptide antibiotic used for Gram-positive bacterial infections, and it has been reported to inhibit SARS-CoV-2 and Ebola virus entry through cathepsin inhibition. Given that TP can inhibit viruses belonging to different virus families, we aimed to expand the potential targets of TP to determine whether TP can be developed as a broad-spectrum antiviral agent. Considering the original indication of TP, we first determined the effects of TP against viruses that cause respiratory tract infections and found that TP inhibits enveloped and non-enveloped RNA viruses, namely: human and avian influenza viruses; representative coronaviruses including porcine epidemic diarrhea virus (PEDV), human coronavirus OC43 (HCoV-OC43), and SARS-CoV-2; measles virus; human respiratory syncytial virus A2; and enterovirus 71 (EV-71). Representative flaviviruses, Zika virus (ZIKV) and dengue virus serotype 2 (DENV2), were also susceptible to inhibition by TP. In contrast, TP did not attenuate infection of human adenovirus 5, a non-enveloped DNA virus. Addition of TP at the endocytosis stage but not at the attachment/binding stage of PEDV infection reduced PEDV production in vitro, indicating cathepsin inhibition. Meanwhile, addition of TP during either the attachment/binding or the endocytosis stage of ZIKV infection reduced ZIKV particle production in host cells, and in silico modeling suggested that TP has potential binding pockets in the envelope proteins of ZIKV and DENV2. These results show that TP can be developed as a broad-spectrum antiviral especially against RNA viruses, with potentially different targets in the replication cycle of various viruses.

microbiology↗