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PubMed2026

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository.

Single-cell RNA sequencing has transformed cell biology by enabling precise transcriptomic measurements of individual cells. The Sequence Read Archive (SRA) is the largest public repository of sequencing reads, yet much of it remains underutilized due to unstandardized metadata. Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. Built by mining all 10x Genomics datasets, scBaseCount is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues. It offers an unbiased view of the data landscape within the SRA and enables the training of more performant computational models through access to broader phenotypic diversity. Uniform processing enables measurement of both intronic and exonic reads and non-coding gene expression and improves alignment across experiments. Moreover, scBaseCount provides a blueprint for how AI can be leveraged to autonomously curate biological data repositories.

Single-Cell Analysis↗

PubMed2026

An open benchmark and language models for AI in aging biology.

Over the past two decades, human aging has been characterized across DNA methylation, transcriptomic, proteomic, and clinical modalities, yet no benchmark evaluates whether AI systems can interpret these heterogeneous data types in the context of aging biology. We introduce LongevityBench, an open suite of 17 tasks spanning five biodata domains, and use it to assess 18 frontier AI systems from six developer teams. Despite recent advances in AI, no single model dominates all tasks, with omics-based age prediction being the hardest task regardless of scale. To test whether these gaps can be closed without frontier-scale resources, we fine-tuned a family of five multitask Longevity-LLMs on domain-specific aging data. The compact (0.6B-9B parameters) Longevity-LLMs matched or exceeded far larger frontier systems on LongevityBench, showing that general-purpose language models can be adapted to structured-omics tasks. We publicly release the benchmark, models, and Longevity Claw, an agentic research interface for aging researchers.

Aging↗

PubMed2026

Phosphate backbone epitranscriptomics: Discovery of natural RNA phosphorothioates and their writer machinery.

Over 150 modifications expand the RNA alphabet, yet all known natural modifications occur on nucleobases or ribose sugars, with none identified on the phosphate backbone. In contrast, phosphorothioates (PSs), in which a non-bridging phosphate oxygen is replaced with sulfur, are central to RNA therapeutics but have never been reliably detected in natural RNAs. Here, we develop sequencing- and mass spectrometry-based approaches to quantitatively map RNA PSs at single-nucleotide resolution. Across diverse archaeal species, we identify stereospecific PS modifications at rRNA and tRNA hotspots, which are dynamically regulated by sulfur availability and temperature. We uncover a diverse enzyme family that selectively modifies tRNA/rRNA substrates and whose evolutionary presence/absence matches the distribution of PSs. Enzyme loss causes inviability or temperature sensitivity, and functional analyses reveal that tRNA PSs enhance tRNA stability. These findings establish the first natural RNA phosphate-backbone modification and its enzymatic machinery, providing a foundation for mechanistic and functional exploration.

RNA modifications↗

PubMed2026

Tahoe-100M: Mapping drug-induced molecular phenotypes at single-cell resolution.

We present Tahoe-100M, a giga-scale single-cell perturbation atlas comprising 100 million transcriptomes from 50 diverse cancer cell lines treated with 1,100 drug-dose conditions. This parallel profiling of thousands of perturbations at single-cell resolution with minimal batch effects is enabled by the Mosaic platform, which multiplexes genetically distinct cell models into balanced "cell villages." Beyond cataloging transcriptomic shifts, Tahoe-100M systematically quantifies cellular phenotypes, including proliferation, cytotoxicity, lineage-specific vulnerabilities, and cell-cycle changes. It captures population-level transcriptomic heterogeneity, characterizing whether drug responses drive cells toward divergent fates or convergent states. Pathway-based signatures define drug-induced expression programs, classify mechanisms of action, reveal off-target activities, and expose adaptive stress responses associated with resistance. By unifying cellular and molecular readouts, this broadly applicable perturbation atlas advances our ability to model gene regulation, drug response, and network dynamics. Its public release enables the training of AI frameworks to advance predictive models of cell behavior.

Humans↗

PubMed2026

Spontaneous lytic reactivation drives a persistent B cell-vector pathway for epithelial dissemination of the Epstein-Barr virus.

The Epstein-Barr virus (EBV) establishes lifelong B cell infection via oral transmission; however, it paradoxically drives carcinomas in anatomically distant organs with striking geographic disparities. While genomic studies frequently link specific EBV variants to these epithelial cancers, the mechanisms bridging ubiquitous infection to distant, strain-dependent malignancies remain largely unresolved. Using an induction-free primary B cell system, we identify a circulating B cell-vector pathway driving immortalized epithelial dissemination. We demonstrate that B cells infected with carcinoma-associated strains exhibit markedly higher epithelial transmission compared with those carrying lymphoid strains. This contact-dependent process requires spontaneous lytic reactivation, viral DNA replication, and de novo virion production. Crucially, those infected B cells retain their transmission capacity for months, supporting sustained epithelial seeding. Mechanistically, entry requires gH/gL engagement of EphA2/desmocollin-2 (DSC2), with actin- and PI3K-dependent endocytosis. These findings define a lytic-coupled, receptor-dependent pathway by which the EBV exploits B cells to access the epithelium, offering a mechanistic framework for understanding strain tropism and host-virus interactions.

B cell vector↗

PubMed2026

A CsWRKY46-CsPBL9-CsARI1 tripartite regulatory module coordinates H2O2 production and callose deposition in citrus fruit immunity.

Plant immunity against pathogens involves multiple immune responses and intricate regulatory networks. However, how immune networks are deployed in fruit remains poorly understood. Here, we show that citrus fruit immune responses, including hydrogen peroxide (H2O2) production and callose deposition, are multiply regulated by transcriptional activation, phosphorylation, and ubiquitination. Citrus sinensis genes encoding nicotinamide adenine dinucleotide phosphate (NADPH) oxidase CsRBOHG and callose synthase CsCalS5, responsible for H2O2 production and callose deposition, respectively, are transcriptionally activated by CsWRKY46. Phosphorylation-enhanced activity of CsRBOHG by CsPBL9 enhances immunity. RING1-IBR-RING2 (RBR)-type E3 ligase CsARI1, acting as an immune brake, ubiquitinates CsRBOHG and CsCalS5 for degradation. Interestingly, CsARI1 also shows a moonlight function wherein it interacts with CsPBL9 in a non-ubiquitination manner, disrupting CsPBL9's interaction with CsRBOHG. This CsARI1-CsPBL9 interaction is stimulated by H2O2 as feedback. Moreover, H2O2 contributes to callose deposition, indicating an interplay between two immune responses. Our study reveals a tripartite regulatory hub orchestrating self-linked immunity in citrus fruit.

CP: plants↗

PubMed2026

Tail-degloving and cold storage facilitate primary cell culture from wild-caught rodents.

The use of wild rodents as biological resources is hindered by the difficulties of live transport and primary culture contamination caused by skin bacteria. To address this, we developed a "tail-degloving" method to physically remove the contaminated external integument. Using the large Japanese field mouse (Apodemus speciosus), this method suppressed contamination compared to conventional biopsies, yielding cells within 5-7 days that were capable of subculturing and cryopreservation. The protocol withstood 4°C storage for up to 7 days and enabled contamination-free cell establishment from a large rodent. This tail-degloving protocol eliminates live transport risks and effectively establishes primary cells after a multi-day transport delay.

Aseptic sampling↗

PubMed2026

Evolutionary patterns and repeated adaptive strategies of deep-sea anemones.

Sea anemones occupy the full depth range of the oceans, yet their evolutionary patterns and adaptive strategies to the enigmatic deep sea have remained contentious and poorly resolved. Here, we assemble genomes (n = 13) and transcriptomes for 15 species collected between 432 and 6,000 m and integrate them with publicly available actiniarian data. We find support for a shallow-water origin of Actiniaria through a framework that emphasizes genome-scale changes associated with habitat transitions. Most strikingly, these changes include repeated dismantling of the circadian toolkit across deep-sea lineages. In addition to convergent gene losses in photo- and temperature-regulatory genes, we find that some deep-sea lineages have experienced recurrent loss or pseudogenization of key meiotic genes (e.g., Meiosin, Ythdc2, Spo11, and Mlh3), suggesting reduced meiotic capacity in some lineages. Despite this extensive genomic erosion, deep-sea anemones exhibit molecular tuning: specific amino acid substitutions improve enzyme performance under low-temperature conditions relevant to the deep sea, while selective expansions of gene families related to neural excitability, membrane systems, and other functions may help maintain physiological performance in this environment. Functional assays in yeast indicate enhanced performance of the deep-sea variants at 4°C. These results define a "loss-optimization-innovation" triad that underlies bathymetric adaptations and may apply to other deep-sea fauna worldwide.

Actiniaria↗

PubMed2026

Phylogenomics and museomics reveal five distinct species of tiger cats in South America.

The evolutionary history of elusive organisms can be characterized through genomic analyses, which have the power to reveal previously unknown taxa even in groups assumed to be well studied, such as cats. We have analyzed complete genomes of 38 individuals from the Neotropical cat genus Leopardus, including 26 individuals representing multiple evolutionary units of the contentious tiger cat (Leopardus tigrinus) species complex. Eight genomes were generated from museum specimens, which allowed the first genetic assessment of the type locality for L. tigrinus in the Guiana Shield. We found that this complex comprises five distinct species, including a novel cat species, discovered in the Bolivian Yungas and described in this study as L. tilcayo. The Peruvian Yungas unit of this complex also represents a distinct taxonomic entity, which we describe here as a novel subspecies, L. tigrinus antisuyo. Our phylogenomic analyses resolve the evolutionary relationships among the tiger cat geographic units, thus stabilizing their recalcitrant taxonomy and enabling adequate conservation assessment of these threatened felids. We also address other aspects of their evolution, including biogeography, past episodes of interspecies admixture, demographic history of each taxonomic unit, and temporal changes in genetic diversity. Altogether, our results clarify the evolutionary history of a complex radiation of wild cats, reveal novel taxa, and serve as a basis for conservation planning on behalf of these elusive wild cats.

Bolivian Yungas↗

PubMed2026

Quantifying the control laws governing terminal attack in lions.

Intercepting an evasive, maneuvering target is among the most computationally demanding tasks a predator performs: in the terminal phase of a chase, it must continuously convert sensory information about the target into steering and speed commands, subject to its own biomechanical limits. How terrestrial predators solve this in real time has remained difficult to quantify. Here, we combine drone videography with AI-based markerless pose estimation to reconstruct the kinematics of 67 lion (Panthera leo) attacks on a mechanized lure programmed to move unpredictably. Lion steering is described by a combination of proportional navigation and proportional pursuit, which is a mixed guidance law previously identified only in the aerial pursuit of Harris's hawks (Parabuteo unicinctus), and speed is regulated within a defined kinematic envelope during turns, which declines at close range where the cost of overshooting is greatest. These findings reveal shared guidance principles across aerial and terrestrial pursuit, thus providing a quantitative framework for comparing pursuit strategies across species.

computational ethology↗

PubMed2026

Antibacterial mechanisms and pathogen-dependent protective effects of the golden pompano LEAP2-derived peptide TroLEAP2-21.

Antimicrobial peptides (AMPs) are essential components of the innate immune system, with liver-expressed antimicrobial peptide 2 (LEAP2) playing a pivotal role in fish immunity. This study investigated the antimicrobial activity and mechanisms of TroLEAP2-21, a 21-amino-acid short peptide from golden pompano (Trachinotus ovatus), against Gram-positive (Lactococcus garvieae, Staphylococcus epidermidis) and Gram-negative (Vibrio alginolyticus, Vibrio harveyi) bacteria. The predicted three-dimensional structure and helical wheel projection of TroLEAP2-21 suggested typical AMP-like physicochemical features. troleap2 expression in the liver and intestine of T. ovatus was significantly upregulated post L. garvieae or V. harveyi infection, suggesting its potential involvement in antibacterial defense. In vitro, TroLEAP2-21 exhibited antibacterial activity against the tested bacterial strains, with membrane disruption, increased membrane permeability, cytoplasmic leakage, and membrane depolarization observed after peptide treatment. Gel retardation assays further indicated species-dependent association of TroLEAP2-21 with bacterial genomic DNA. In vivo, under the tested intraperitoneal injection conditions, TroLEAP2-21 was associated with improved survival and reduced tissue damage in V. harveyi-infected T. ovatus, whereas no significant survival benefit was observed against L. garvieae. Transcriptomic analysis at 48 h post-infection showed transcriptional changes in immune-related DEGs (rsad2, mx1/mx2, il-8) and enrichment of TLR and Jak-STAT signaling pathways at the transcriptional level in peptide-treated fish. FISH showed the tissue localization of tnf-α and nf-κb transcripts and revealed treatment-associated changes in fluorescence signals, and qRT-PCR of eight immune genes supported transcriptomic results in tissues at 48 h post-infection. Collectively, these findings characterize TroLEAP2-21 as a short LEAP2-derived peptide with antibacterial and immunomodulatory activities. Its comparative advantages over other LEAP2-related peptides and its practical application potential remain to be further investigated.

AMPs↗

PubMed2026

Silent carriage of tigecycline- and carbapenem-resistant Klebsiella quasipneumoniae co-harbouring tetX(4) and blaNDM-1 in healthy individuals in China.

OBJECTIVES: To investigate the occurrence and genomic characteristics of tigecycline- and carbapenem-resistant Klebsiella quasipneumoniae isolated from healthy individuals in China. METHODS: During a nationwide screening programme, faecal samples from healthy community individuals were cultured for carbapenem-resistant Enterobacterales. Antimicrobial susceptibility testing, whole-genome sequencing and conjugation assays were performed for two K. quasipneumoniae isolates co-harbouring tet(X4) and blaNDM-1. RESULTS: Two K. quasipneumoniae strains carrying tet(X4) and blaNDM-1 were recovered from healthy individuals without recent hospitalisation or antibiotic exposure. Both isolates showed resistance to tigecycline (>8 μg/mL) and carbapenems (≥4 μg/mL). Genomic analysis demonstrated close clonal relatedness between the isolates (ST6460-1LV, KL151). The blaNDM-1 gene was located on an IncX3 plasmid associated with mobile genetic elements, whereas tet(X4) was carried by an IncX1 plasmid. Conjugation assays confirmed successful transfer of both resistance genes, which frequently co-transferred into recipient strains. CONCLUSIONS: To our knowledge, this is the first report of K. quasipneumoniae co-harbouring tet(X4) and blaNDM-1 in healthy individuals in China. The findings indicate that healthy community populations may serve as a hidden reservoir for last-resort antimicrobial resistance genes and underscore the importance of community-based surveillance within a One Health framework.

Klebsiella quasipneumoniae↗

PubMed2026

A Pilot Study on the Utility of Whole Genome Sequencing for Detecting Drug Resistance in Mycobacterium tuberculosis in the Current Scenario.

PURPOSE: Whole Genome Sequencing (WGS) comprehensively detects all drug-resistant mutants, which can help in the early initiation of specific treatment for the patient. But there is a need to evaluate the performance of WGS in comparison with Line Probe Assays (LPA) and Phenotypic Drug Susceptibility Tests (pDST). METHODS: Consecutive sputum samples (58) found positive for Mycobacterium tuberculosis (MTB) by GeneXpert were tested for first-and second-line LPA, pDST and WGS for anti-tubercular drugs. RESULTS: Of 58, 34 (58.6%) culture isolates were resistant to one or more drugs. Resistance detected by WGS was as follows: Isoniazid 23(39.6%), Rifampicin 21(36.2%), FQs 21(36.2%), Ethambutol 18(31%), Linezolid 12(20.6%), Streptomycin 8(13.8%), Kanamycin 6(10.3%), Amikacin and Capreomycin 5(8.6%), Para-amino salicylic acid 1(1.7%) and Ethionamide 1(1.7%). No resistance was detected to Pyrazinamide, Bedaquiline, Clofazimine, Delamanid and Pretomanid. Lineage 3(EAI) was the most predominant 23(39.6%) followed by Lineage 2: 13(22.4%). Intermediate Resistance (IR) and potential novel mutations were observed in a few cases, CONCLUSION: Overall accuracy for first-line drugs between pDST vs WGS was >98% &pDST vs LPA >95%, while for second-line drugs accuracy was >96% and >90% respectively. IR and potential novel mutations should be followed up closely to understand their clinical significance.

IR↗

PubMed2026

The Staphylococcus aureus serine protease-like protein B is a potent allergen in a murine asthma model.

BACKGROUND: Asthma is associated with Staphylococcus aureus colonization. Two hypotheses were proposed to explain this phenomenon: (1) the allergic environment in asthma favors S. aureus colonization and (2) S. aureus colonization creates a pro-allergic environment. Since several S. aureus virulence factors, such as the serine protease-like protein (Spl) B, elicit a type 2 biased immune response, we asked whether the pathogen itself can cause asthma. OBJECTIVE: Test the ability of recombinant SplB of S. aureus to sensitize mice and induce allergic airway inflammation (AAI). METHODS: Mice were treated with repeated intratracheal inoculations of either catalytically active SplB or an inactive mutant. AAI was assessed by evaluating airway hypersensitivity, immune cell infiltration, cytokines, mucus production, fibrosis, and specific serum IgE. We compared the outcome between wild-type and gene-deficient C57BL/6J mice, including recombination-activating gene knockout mice (Rag2-/-), interleukin-33 knockout mice (Il33-/-), and protease-activated receptor 2 knockout mice (F2rl1-/-). RESULTS: Intratracheal exposure to SplB sensitized the mice and caused eosinophilic airway inflammation and hyperresponsiveness. The development of asthma required both the proteolytic activity of SplB and a functional adaptive immune system. The soluble protease sensor IL-33 was necessary for eosinophil tissue invasion, whereas the membrane-bound protease sensor PAR2 was not. CONCLUSION: The serine protease SplB of S. aureus is a potent allergen. Based on this finding we propose a third mechanism to explain the relationship between S. aureus colonization and asthma: S. aureus can release allergens, such as SplB, that sensitize individuals and lead to the development of asthma.

Allergy↗

PubMed2026

Reframing the asthma microbiome: Multikingdom, multisite, and multiomic perspectives.

The field of asthma microbiome research has shifted rapidly in recent years. Advances in sequencing technology have led to an increased ability to characterize multikingdom microbial species and integration with host -omics profiling to enhance future translational applications. Traditional bacteria-centric, cross-sectional studies are giving way to mechanistic frameworks that incorporate fungi, viruses, and host-immune interactions. In this state-of-the-art review of emerging concepts in microbiome asthma research, we first propose a structured framework to consider microbiome studies across 5 major domains-microbial kingdom, site of sampling, integration with host -omics, clinical outcome domain, and translational relevance-in order to synthesize recent high-impact human microbiome studies in asthma. We highlight emerging evidence that fungal and viral communities contribute independently to asthma risk and that human microbial communities are linked to distinct inflammatory and immune pathways shaped by host genetic susceptibility.

Asthma↗

PubMed2026

Metagenome-resolved evidence that soluble factors in granular activated carbon-amended reactor effluent reprogram propionate metabolism and methanogenic pathways.

Granular activated carbon (GAC) enhances anaerobic digestion performance, yet the mechanisms underlying reactor-scale improvements remain incompletely understood, particularly how GAC affects biomass not attached to its surface. Here, sludge from a non-GAC up-flow anaerobic sludge blanket reactor was incubated with 0.45-μm-filtered effluents from non-GAC and GAC-amended reactors under repeated propionate loading, followed by genome-resolved metagenomics. GAC-reactor effluent increased methane yield from 64 ± 3% to 76 ± 3% (p < 0.01) in the absence of GAC particles. A non-redundant catalog of 170 quality-filtered metagenome-assembled genomes (MAGs) was recovered, enabling pathway- and gene-set quantification. Genomic potential for both major propionate-oxidation routes increased in the GAC-effluent group relative to the non-GAC group, with a larger increase for the methylmalonyl-CoA (MMC) route than for the dismutation route (1.289- versus 1.221-fold). Accordingly, the MMC-to-dismutation preference ratio was 5.60% higher in the GAC-effluent group, alongside a broader carrier base. Cobamide potential shifted toward remodeling and cobamide-dependent use rather than increased de novo corrin-ring synthesis. Candidate electron-transfer architectures were also rebalanced: PilA-associated carriers became less prominent, whereas maturation-supported multiheme cytochrome carriers increased from 22.96% to 34.90% of community abundance, although H2/formate-module carriers remained prevalent. Quorum-sensing systems underwent pathway- and carrier-specific redistribution, while all eight curated extracellular-polysaccharide modules showed higher mean gene abundance in the GAC-effluent composite. These findings show that a filter-passing effluent fraction can extend GAC-associated effects beyond direct particle contact and link enhanced methanogenesis to a broader, redistributed network of metabolic, redox, and coordination capacities. This expands the mechanistic framework of conductive-material-assisted anaerobic digestion and provides a basis for harnessing GAC-derived functions throughout the reactor.

Extracellular polymeric substances (EPS)↗

PubMed2026

Complete genome sequence of an antibiotic-resistant and virulent Escherichia marmotae isolate recovered from a urinary tract infection.

OBJECTIVES: We aimed at analyzing the whole genome of the antibiotic-resistant Escherichia marmotae isolate 23-MO01035-0, which was obtained from a urinary tract infection of a male patient in Germany. The study focused on the characterization of mobile genetic elements and genetic factors that contribute to antibiotic resistance and pathogenicity. METHODS: Phenotypic antimicrobial susceptibility testing was performed and genomic DNA was sequenced using Illumina NextSeq (2 × 151 bp) and a MinION Mk1C device followed by de novo hybrid assembly using Unicycler v0.4.8. Resistance genes, virulence factors, plasmids, and mobile elements were identified with the bakcharak pipeline and PathogenFinder. RESULTS: The isolate belonged to sequence type ST133 and the 5,041,084 bp whole genome, consisting of one chromosome and five plasmids with an average GC content of 50.4%, revealed resistance genes for various antibiotic classes on an IncFII plasmid that had not yet been described. The isolate was predicted to be a potential human pathogen due to the presence of multiple virulence genes. CONCLUSION: Here, we report one of the first detailed genomic characterization of an antibiotic-resistant and virulent E. marmotae isolate from Germany. Considering that this bacterium was isolated from the urinary tract and possibly belonged to the faecal microbiota of the patient at that time, E. marmotae might contribute to the spread of antibiotic resistance in humans. This underscores the importance of genomic surveillance of E. marmotae, which causes human infections, but may be misidentified as E. coli.

Escherichia marmotae↗

PubMed2026

Promises and Pitfalls of ctDNA testing in the Management of Cholangiocarcinoma.

Diagnosis and treatment of cholangiocarcinoma is often limited by the availability of tissue biopsies for genomic analysis. Liquid biopsies using blood circulating tumor DNA (ctDNA) have emerged as a valuable and non-invasive alternative to conventional testing. ctDNA analysis has advanced the treatment paradigm for cholangiocarcinoma (CCA) by identifying targetable mutations and molecular mechanisms of treatment resistance. Additionally, it has shown preliminary promise in stratifying patients for adjuvant systemic therapy and enabling earlier detection of relapse. However, current ctDNA platforms face biological and technical challenges that limit their sensitivity for certain mutation types (i.e. gene fusions and amplifications), which are commonly found in CCA. To overcome these hurdles, new sequencing techniques and analytic methods involving artificial intelligence, epigenetic profiling, and diverse reference genomes are being developed. These advanced technologies underscore the promise of ctDNA testing as an indispensable tool in the management and study of CCAs.

Cholangiocarcinoma↗