Biology subjects

Li, G.

Publications and source records attributed to Li, G..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Evolutionary dynamics of insect odorant receptors reveal ecological tuning shaping olfactory perception

Insect olfaction is facilitated by a heterotetrameric odorant receptor-odorant receptor co-receptor (OR-Orco) complex, which is distinct from that of vertebrate ORs. However, extreme sequence divergence among insect ORs has hindered a unified understanding of their evolutionary history and ecological importance. In this study, we present a multiscale analysis of OR genes across 115 insect species. We overcome the limitations of traditional phylogenetic approaches by applying a protein similarity network-based strategy and introduce a "trunk-branch" framework to systematically describe the evolutionary trajectories of insect ORs across sequence, structural, and predicted olfactory potential levels. Although they possess different sequences and structural communities, all sampled insect orders contained ORs assigned to all six docking-derived functional communities. Notably, extant insect lineages with order-level origins spanning the end-Permian mass extinction (EPME) differed in docking-derived functional OR repertoires, and early-and late-diverging lineages differed in OR sequence-community diversity. The emergence of Orco represents a key evolutionary transition point, marking the shift from a homomeric to a heteromeric complex accompanied by specialization of the extracellular domain and binding pocket. Furthermore, we established robust associations between potential olfactory recognition breadth and ecological variables, including diet, circadian rhythm, and habitat. Our findings provide a class-level framework for investigating insect OR evolution and generate testable hypotheses about how receptor repertoire diversification may relate to ecological adaptation.

evolutionary biology↗

bioRxiv2026

Elimination of intramuscular immunoglobulin accumulation alleviates Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disorder due to loss of dystrophin, a cytoskeletal protein critical for muscle integrity and functionality. Despite recent therapeutic advances, there remains a significant unmet need for more effective and accessible therapeutics. Here, we discovered an early accumulation of immunoglobulin G (IgG) in the sarcolemma, which exacerbates tissue inflammation and disease progression. The IgG accumulation primarily resulted from ectopic localization of Fc{gamma}R1, a high-affinity IgG Fc receptor, on dystrophin-deficient myofibers. In two independent murine models, eliminating IgG accumulation via B cell depletion provided sustained benefit to alleviate DMD progression. Our findings uncover a novel disease accelerator in DMD and demonstrate the potential to target this mechanism as therapeutics for broader population of patients with DMD.

immunology↗

bioRxiv2026

Viral haplotype reconstruction from long reads with virCHap

Resolving genomes at the haplotype level for viral populations is crucial for understanding the prevalence of viral diseases and for the development of effective therapeutic treatments. However, viral haplotype reconstruction still presents challenges, such as an unknown number of strains, high inter-strain similarity, repetitive regions, and difficulties in abundance estimation. Here, we developed virCHap, a new reference-based haplotype phasing algorithm for viruses, which applies graph partitioning followed by iteratively quantifiable cluster merging on long-read sequencing data. Benchmarking on simulated and real datasets demonstrates that virCHap outperforms current tools in terms of recall, accurate abundance estimates and read clustering accuracy. On the simulated large-genome VZV experiment, virCHap had a 96.5% recall, 14% higher than the second-best method, and had the most accurate abundance estimates. On a real 5-strain PVY dataset, virCHap had a precision exceeding 92.9%, a recall of over 97%, and a read clustering accuracy of 82%, outperforming the second-best method by 32%. On a real 6-strain SARS-CoV-2 dataset, virCHap achieved >96.9% accuracy, and the most accurate abundance estimates within the spike gene.

bioinformatics↗

bioRxiv2026

Segmental outflow and trabecular meshwork stiffness in an ocular hypertensive mouse model

PurposeElevated intraocular pressure (IOP) due to increased outflow resistance through the trabecular meshwork (TM) is a major risk factor for primary open-angle glaucoma. Outflow through the TM is segmental, consisting of high flow (HF) and low flow (LF) regions. Here, we investigate how ocular hypertension impacts segmental outflow using a dexamethasone (DEX) mouse model and compare TM stiffness between HF and LF regions. MethodsNanoparticles containing DEX or vehicle were injected twice weekly in 2-4-month-old C57BL/6J mice (n=14), and IOP was measured weekly. At week 4, mouse eyes were perfused in vivo with fluorescent nanospheres to assess flow patterns and the circumferential percentage of high, intermediate, and low flow regions in each eye. Sagittal sections were collected from HF and LF regions, and atomic force microscopy (AFM) was used to measure tissue stiffness. Immunofluorescent labeling was used to compare fibronectin and -SMA protein levels. ResultsDEX treatment significantly elevated IOP by an average of 33.3% and altered tracer distribution but not the percentage of HF and LF regions around the circumference. No significant differences in TM stiffness were detected between DEX-treated and control mice, or between HF and LF regions. Increased fibronectin in LF regions of DEX-treated eyes suggested subtle TM structural changes that were not detected by AFM. ConclusionsDexamethasone alters segmental flow distribution and may impact cell contractility rather than ECM stiffness to cause IOP elevation in young mice. These findings better characterize the nature of segmental outflow and TM mechanics in this model of steroid-induced glaucoma.

bioengineering↗

bioRxiv2026

An agentic framework turns patient-sourced records into a multimodal map of ALS heterogeneity

ALS progression is multidimensional, yet fragmented records and scalar outcomes obscure how patients move through disease states and how those states relate to molecular variation. MEDSTREM converts patient-held medical-record images into standardised longitudinal data, enabling bottom-up cohort construction. Using MEDSTREM-structured records from more than 8,000 AskHelpU participants together with PRO-ACT and Answer ALS, we developed DynaALS, the ALS Disease Dynamics Atlas. DynaALS represents ALS as a dynamic patient-state manifold that captures distinct directions of deterioration and patient movement between them over time. DynaALS retrieved population-referenced future states and decoded them into multidimensional clinical profiles without requiring patient-specific longitudinal histories. Motor-neuron RNA and chromatin profiles linked DynaALS states to developmental and regulatory programs, while neuromuscular-organoid single-cell multi-omics converged on a neural-developmental Netrin-DCC signalling axis across interacting cell types. By coupling MEDSTREM-enabled data construction to dynamic state modelling, DynaALS establishes a transferable patient-state engine for predictive and biologically interpretable disease models.

bioinformatics↗

bioRxiv2026

Unconstrained Plasticity Disrupts Memory Consolidation in a Mouse Model of Rett Syndrome

Memory impairment is a hallmark cognitive deficit in Rett syndrome (RTT). Yet, long-term memory deficits in RTT animal models remain poorly understood, largely due to the technical challenges inherent in tracking neural activity over extended periods. Here, we used longitudinal two-photon calcium imaging to follow the same population of hippocampal CA1 neurons as female RTT mice and their littermate controls formed cognitive maps of their environment during a spatial learning task. Neural representations in RTT mice were marked by excessive place cell (PC) activity, with individual PCs exhibiting pronounced instability across days. This disrupted single-cell stability propagated to the population level, resulting in unstable ensemble codes that poorly retained previously learned task information. Both excessive PC recruitment and instability could be attributed to a higher incidence of behavioral timescale synaptic plasticity (BTSP) in RTT mice. In wild-type littermates, place-cell consolidation across days is reflected by an increased likelihood of neuron-specific synaptic plasticity at the location of prior PC coding. This cellular mechanism of memory consolidation based on the location of BTSP was disrupted in RTT mice, where excessive and ectopic plasticity reduced PC stability, and degraded long-term stable representations. Backed by theoretical modeling, these results identify a plausible cellular and circuit-level mechanism underlying memory impairments in RTT mice and suggest principles that may be generalized to other neurological disorders involving memory deficits.

neuroscience↗

bioRxiv2026

CMTM6-Silencing Microbial Immunotherapy Reprograms PDAC Tumors and Restores T-cell Function

Despite recent advances in immunotherapy for advanced malignancies, Pancreatic ductal adenocarcinoma (PDAC) remains largely refractory to current immunotherapy due to dense fibrosis, limited antigen presentation, and myeloid-driven immune suppression. Here we report the tumor-targeting, immune remodeling, and safety profiles of the attenuated Salmonella enterica serovar Typhimurium strain CRC2631, and of iSTORM, a next-generation derivative engineered for tumor-localized CMTM6 silencing. CRC2631 preferentially colonizes orthotopic and genetically engineered PDAC tumors, with enrichment in primary lesions and metastases. Tumor-localized CRC2631 induces chemokine and adhesion programs consistent with leukocyte recruitment, increases intratumoral activated T-cell fractions, and triggers transcriptional signatures aligned with innate sensing, interferon signaling, antigen-processing and presentation, and apoptosis programs. iSTORM extends this platform by delivering CMTM6-targeting shRNA to modulate a PD-L1-stabilizing, myeloid-associated immune-evasion programs within tumor-colonized tissue. Compared with CRC2631, iSTORM increases intratumoral CD8+ T cells, shifts T-cell state toward activation with reduced exhaustion-prone features, strengthens antigen-presentation programs, and achieves deeper tumor control. A lyophilized formulation preserves immune remodeling while improving deployability. Mechanistically, glycan arrays and functional studies support mannose-rich glycan-guided tumor engagement. iSTORM toxicity studies, including systemic cytokine, hematologic, blood chemistry, and lethality demonstrate a favorable safety profile. Collectively, these findings establish iSTORM as a safe, programmable, CMTM6-silencing microbial immunotherapy platform that selectively targets and penetrate PDAC tumors to unleash anti-tumor immune activities. What is already known on this topicPDAC is highly resistant to immune checkpoint blockade because dense stroma and myeloid-dominated suppression prevent effective T-cell infiltration; attenuated Salmonella strains can selectively colonize tumors but first-generation agents showed limited efficacy and safety concerns. What this study addsThis study defines CRC2631/iSTORM as a tumor-selective microbial immunotherapy that exploits surface-exposed, mannose-rich N-glycans to colonize PDAC, delivers CMTM6 silencing, and restores CD8+ T-cell activation and tumor control in models resistant to PD-1 blockade immunotherapy. How this study might affect research, practice or policyThese findings provide a mechanistic blueprint for glycan-guided, CMTM6-targeted bacterial "living drugs," support rational combination strategies for deepening therapeutic effect, and establish a lyophilized, biocontained platform that could be developed into scalable microbial immunotherapies for PDAC and other immunologically cold solid tumors.

cancer biology↗

bioRxiv2026

MicroRNA regulatory targets of VO2peak in older adult participants of the Study of Muscle Mobility and Aging (SOMMA)

Skeletal muscle aging (sarcopenia) is associated with reduced peak oxygen consumption (VO peak) during exercise, a key determinant of physical function and overall health. However, the molecular mechanisms linking muscle aging to low VO peak remain poorly understood. We aimed to identify miRNA signatures and miRNA-gene regulatory networks associated with VO peak in older adults. Using small RNA and mRNA sequencing, we analyzed skeletal muscle from 72 SOMMA participants (70-79 years old) with low or high VO peak (n = 18/group) and from 36 participants spanning the full VO peak spectrum. Differential expression was assessed using LIMMA, with pathway and network analyses performed using Ingenuity Pathway Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA). We detected 1,408 miRNAs and 16,210 genes; among these, 14 miRNAs and 2,018 genes were differentially expressed (FDR < 0.05). The 14 miRNAs regulated 142 genes, and expression of 10 miRNAs inversely correlated with 50 genes enriched in mitochondrial, sirtuin-1, and nitric oxide signaling pathways. Regression analyses identified 21 miRNAs and 1,744 genes significantly correlated with VO peak after adjusting for age and sex. WGCNA revealed 10 co-expression modules associated with VO peak, with the cyan module showing the strongest correlation and enrichment for nitric oxide signaling genes. These findings highlight novel miRNA-mediated molecular pathways potentially contributing to low VO peak and skeletal muscle aging in older adults. Future studies will further investigate these miRNA-gene interactions to uncover therapeutic targets for preserving muscle function with age.

molecular biology↗

bioRxiv2026

Scalable Generation of Clinical-Grade Universal Human cDC1s Enables Potent Antitumor Immunotherapy

Despite decades of intensive clinical effort, monocyte-derived dendritic cell (DC) vaccines have not yet achieved sufficient clinical benefits in cancer therapy. Conventional type 1 DCs (cDC1s), a subset of antigen-presenting cells with superior cross-presentation capacity, are well established as pivotal mediators of antitumor immunity. However, their clinical translation has been hindered by the absence of scalable and efficient generation methods. Here, we develop a three-step strategy addressing this critical unmet need: a cost-effective, feeder cell-free, GMP-compatible approach enabling large-scale generation of cDC1s from human umbilical cord blood CD34+ hematopoietic stem and progenitor cells (CD34+ HSPCs). Starting from a single umbilical cord blood unit of CD34+ HSPCs, our method yields approximately 3.5x109 pure cDC1s--sufficient for over 700 therapeutic doses. These cDC1s exhibit robust antigen cross-presentation activity and substantial production of antitumor cytokines. Critically, in various humanized tumor mouse models, they elicit significantly stronger antitumor efficacy than either moDCs or PD-1 monoclonal antibody (mAb) alone, pronouncedly remodel the tumor microenvironment (TME), and synergize with PD-1 mAbs to achieve enhanced therapeutic effects. Furthermore, our system recapitulates the complete in vivo DC differentiation trajectory: from CD34+ HSPCs through early-pre-DCs and pre-DCs to mature subsets (cDC1s, cDC2s, DC3s, mregDCs, ASDCs). This platform thus provides a powerful tool to dissect the regulatory mechanisms governing human DC subset specification. Overall, this work overcomes a long-standing bottleneck in cDC1-directed cancer immunotherapy and accelerates the clinical translation of DC subset-selective immunotherapeutic strategies.

immunology↗

bioRxiv2026

Joint Segmental Duplication Co-option Drives Human-specific Transcriptional Readthrough and Expression Fine-tuning of NPEPPS-TBC1D3

Segmental duplication (SD) is a major driver of functional changes in evolution and disease. Many genes embedded within SDs, such as NPEPPS and TBC1D3, display substantial copy number variation (CNV) across individuals. Yet, the precise identification of the functional copies and their transcriptional outputs remains largely unstudied. Focusing on NPEPPS and TBC1D3, we illustrate human-specific expression fine-tuning mechanisms associated with readthrough transcripts. We identified a human-specific NPEPPS-TBC1D3 digenic genomic structure that originated from a joint SD pair and became fixed across populations. Experiments demonstrate that this structure generates NPEPPS-TBC1D3 readthrough transcripts, which are the predominant isoforms of TBC1D3 expression in various cell types, fine-tuning its protein level. Furthermore, a human-specific hypomethylation signal within an upstream CpG island of NPEPPS precisely pinpoints the expressed TBC1D3 paralog. Moreover, we reveal transcriptional readthrough events are [~]3-fold enriched for joint-SD-associated transcriptional readthrough (JSDTR) and identify 109 JSDTR gene pairs, including neurodevelopmentally important pairs and clinically interesting SERF1A/B-SMN1/2. Taken together, our findings comprehensively describe an example of how a joint SD event shaped evolution and suggest that JSDTR is a broad mechanism for the emergence of new functions.

genetics↗

bioRxiv2026

Diet-Driven Gut Microbiome Differences Between Cohabiting Han and Yi Ethnic Groups in Liangshan, China

BackgroundWhile ethnic variations in gut microbiota are well-documented, their persistence in genetically distinct populations sharing the same geographic environment remains poorly understood. This study investigates the Han and Yi ethnic groups cohabiting rural Southwest China, where contrasting dietary traditions persist under identical environmental conditions. MethodsWe analyzed fecal samples from 100 healthy adults (50 Yi/50 Han) using 16S rRNA gene sequencing (V3-V4 region). Dietary intake was quantified via three 24-hour recalls validated with plasma biomarkers. Multivariate analyses (DESeq2, PERMANOVA) controlled for age, sex, and BMI covariates. ResultsYi individuals exhibited significantly higher Prevotellaceae (log2FC=1.82, padj=0.028) and Succinivibrionaceae (log2FC=2.15, padj=0.013) abundances, corresponding to their buckwheat-rich diet (58.5 {+/-} 12.3% vs Han 3.3{+/-}1.8%, p<0.001) Han microbiota showed enriched Bacteroidaceae (log2FC=1.24, padj=0.041), associated with higher animal fat intake (23.6% vs Yi 1.8%, p<0.001) Dietary factors (buckwheat/animal fat intake) explained greater microbiota variation than ethnic genetic ancestry (PERMANOVA R{superscript 2}=0.10 vs 0.07, p < 0.05) ConclusionCohabiting Han and Yi populations maintain distinct gut microbiota compositions primarily driven by dietary differences. These findings highlight diet as a stronger determinant than genetic ancestry in shaping microbial communities under shared environments. Future studies should validate these observations with metagenomic sequencing.

microbiology↗

bioRxiv2026

Periplasmic gatekeeping of phage DNA entry by rSAM enzyme-mediated maturation of an effector with His-X-Ser repeats

In the relentless arms race between bacteria and phages, bacteria have evolved a variety of defense strategies to combat phage infection. However, no bacterial system has been identified that specifically target the phage DNA entry phase. Here, we present a novel bacterial antiphage system, termed HXS, which provides broad-spectrum and robust antiphage activity by interfering with phage DNA entry. The HXS system consists of two radical S-adenosylmethionine (rSAM) enzymes (HxsB and HxsC), a small protein (HxsD), and the effector HxsA with a peptidoglycan-binding domain and five His-Xaa-Ser (HXS) repeats. HxsB/HxsC catalyze rSAM enzyme-dependent maturation of HxsA, including N-terminal processing and a site-specific +8 Da modification, thereby producing a periplasmic effector required for HXS defense. Biochemical evidence supports a model in which the matured effector likely engages incoming DNA electrostatically to arrest entry, establishing an rSAM enzyme-modified protein effector in antiphage defense.

microbiology↗

bioRxiv2026

Gene networks associated with early endosperm proliferation and basal endosperm layer differentiation in maize

Endosperm is a primary source of food and feed globally. Early developmental events including proliferation and cell differentiation in this dedicated seed sink structure are expected be responsive to the availability of photoassimilates and in turn to affect seed size and quality. However, the gene regulatory programs underlying early development of cereal endosperm remain largely unknown. We profiled the maize (Zea mays) endosperm transcriptome during the first four days after pollination using laser-capture microdissection and identified multiple temporal co-expression modules including a subset activated upon fertilization. Our analysis of the associated cis-regulatory elements and co-expressed transcription factor (TF) families enabled us to construct a gene network regulating basal endosperm transfer layer (BETL) differentiation through MYB-related (MYBR) transcription factors and a network of E2F TFs for early endosperm proliferation. We found a significant association of the BETL network with kernel size variation and a contribution of the Glucose-target-of-rapamycin (TOR)-dependent processes to the E2F-mediated regulation of endosperm proliferation. Using the available data, we propose early proliferative development and transfer cell differentiation in endosperm are coordinated via sugar-sensing inputs to ultimately control seed size. Our analysis can guide the development of strategies for improvement of seed composition and yield.

plant biology↗

bioRxiv2025

The natural flavonoid dihydromyricetin targets senescent cells via PRDX2 and alleviates age-related diseases

Aging is a preeminent risk factor for chronic diseases, with cellular senescence as one of the major hallmarks and an effective target to delay, prevent or alleviate age-related disorders. Here we report in vitro screening outputs from a natural medicinal agent (NMA) library, wherein dihydromyricetin (DMY), a natural flavonoid, showed senotherapeutic potential. DMY protected senescent fibroblasts from further DNA damage and attenuated the senescence-associated secretory phenotype (SASP), acting as a senomorphic agent. Proteomics suggested that DMY promotes nuclear translocation of peroxiredoxin 2 (PRDX2), a reactive oxygen species (ROS) scavenger, facilitating DNA repair in senescent cells. In prematurely aged mice, DMY administration mitigated tissue aging changes and age-related physiological decline. In anticancer regimens, DMY improved outcomes of chemotherapy. However, DMY demonstrated senolytic activity against senescent microglial cells, wherein basal PRDX2 expression remains low, by impairing mitochondrial function to promote ROS-mediated apoptosis. In mice developing an Alzheimers disease (AD)-like state, DMY eliminated senescent microglial cells from amyloid {beta}-protein (A{beta}) plaques, alleviating A{beta}-associated pathological phenotypes. Together, our study proposes DMY to be a natural senotherapeutic agent representing a therapeutic solution for mitigating age-related morbidities including but not limited to cancers and AD.

cell biology↗

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

Pulmonary mRNA-LNP Vaccines for Rapid and Durable Protection Against Bacterial Infection

Pulmonary bacterial infections remain a major clinical challenge. Although vaccination reduces infection rates and mortality, the vulnerable post-vaccination immunity gap can still result in infection and vaccine failure. In addition, effective vaccines are unavailable for many clinically important bacterial pathogens. Here, we report a pulmonary mRNA-lipid nanoparticle (mRNA-LNP) vaccine incorporating a novel ionizable lipid engineered for localized high-level expression, which elicits both rapid and durable protections against bacterial lung infections, effectively bridging this critical window of vulnerability. Intratracheal delivery of mRNA-LNP rapidly primes lung neutrophils and macrophages into a transcriptionally pre-activated state, enhancing their phagocytic activity and enabling rapid, antigen-independent bacterial clearance during the early post-vaccination period (approximately 1-7 days). Subsequently, vaccination induces potent antigen-specific adaptive responses, conferring sustained protection against both laboratory and clinical drug-resistant Pseudomonas aeruginosa strains. Single-cell transcriptomics and immune profiling reveal coordinated activation of innate and adaptive immune programs. This dual-phase immune response exemplifies a paradigm-shifting vaccine design that integrates innate and adaptive immunity to confer both immediate and long-term protection. Our findings establish a mechanistic basis for rapid antibacterial defense and highlight pulmonary mRNA-LNP vaccination as a promising strategy for combating respiratory infections.

bioengineering↗

bioRxiv2025

Adapting Epigenetic Clocks for Cell-Free DNA High-Throughput Sequencing Data

Background.Circulating cell-free DNA (cfDNA or ccfDNA) methylation sequencing holds promise for developing epigenetic aging clocks in minimally invasive aging assessment applications. However, current clocks--primarily trained on array-based data--do not readily generalize to methylation profiles of cfDNA, due to stochasticity and uncertainty arising from the limited input amounts of cfDNA and technical characteristics of high-throughput sequencing (HTS) platform. Due to lack of training to correct this uncertainty, direct application of legacy clocks to HTS data will inevitably produce unreliable estimates, introduce predictive discordance and undermine the trustworthiness of epigenetic biomarkers. Despite this urgent challenge, a systematic, model-agnostic framework for adapting existing epigenetic clocks to HTS-based cfDNA data remains lacking. Methods.Here, we generated a dedicated benchmark dataset comprising paired cfDNA and genomic DNA (gDNA), which was replicated and profiled across two methylation arrays and two targeted HTS platforms. We evaluated 53 epigenetic clocks for CpG coverage, reproducibility, cross-platform consistency, and age prediction accuracy. Further, we systematically explored and tested multiple adaptation strategies including depth filtering, beta-value imputation, and transfer learning via model distillation aiming at improving performance and clinical concordance of legacy epigenetic clocks on cfDNA HTS datasets. Results.Our results show that inherent technical noise of HTS platforms compromises diagnostic precision, presenting as a significant burden for applying legacy clocks on cfDNA HTS data. However, this technical limitation can be systematically neutralized. By enforcing stringent sequencing depth protocols ([≥]10x ideally 20x), employing robust algorithmic stabilization (L2-heavy clocks and imputation) and transfer learning, we can effectively isolate genuine physiological aging signals from technical artifacts. Ultimately, an adaptation pipeline incorporating all these methods effectively improved age prediction accuracy and, closed the gap between epigenetically induced aging status and clinically assessed realities. Besides, the pipeline demonstrated improved diagnostic sensitivity for neurodegenerative conditions such as amyotrophic lateral sclerosis, establishing a reliable foundation for non-invasive clinical monitoring. Conclusions.This study provided a comprehensive framework and practical guidelines for adapting epigenetic clocks to HTS-based cfDNA data, paved the path for more general application of cfDNA-based aging assessment and liquid biopsies.

bioinformatics↗

bioRxiv2025

Initial identification of genomic islands in Taylorella equigenitalis and Taylorella asinigenitalis and their distribution in isolates from around the world

Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM), is endemic in several countries throughout the world and impacts the global movement of horses. It presents with symptoms ranging from non-clinical to endometritis, vaginitis, and acute infertility in females while males remain asymptomatic. Studies of the disease have focused primarily on understanding pathology, transmission dynamics, diagnostics, and phenotypic and genotypic characteristics. The goal of this study was to establish a more comprehensive global phylogenetic structure and generate reference-quality genomes for each major clade of the tree where such data were absent. Seven of these genomes along with 44 other publicly available genome assemblies, including Taylorella asinigenitalis, were then used to predict genomic islands. Exploration of the NCBI annotations in the genomic islands indicate links to virulence and ecological fitness. An additional 97 T. equigenitalis and 48 T. asinigenitalis short-read isolates from this study and 215 publicly available genomes were used to examine distribution of each genomic island across the phylogenetic tree for evidence of horizontal movement. The stability of these genomic islands in their natural environment was evaluated utilizing 141 isolates recovered from a recent CEM outbreak in the United States. The results obtained in this study demonstrate mobile genomic islands in T. equigenitalis genomes, sites of concern for their contribution to the potential virulence of the organism.

microbiology↗