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Kong, J.

Publications and source records attributed to Kong, J..

At least 19 recordsLinked to original sources

Substrate-induced asymmetry coordinates lipoprotein handover and abaucin trapping in Acinetobacter baumannii LolDF

The homodimeric lipoprotein transporter LolDF supports outer-membrane biogenesis in Acinetobacter baumannii. How homodimeric LolDF generates directional lipoprotein transport, and how the reported two- and four-abaucin states are related, remain unclear. Using defined lipidated AbLolB and AbLolA, we show that substrate binding breaks LolF symmetry: LolFB primarily accommodates the lipid anchor, LolFA positions the adjacent polypeptide, and LolA docks asymmetrically through the LolF hook and an AbLolA-specific loop. C1 reconstruction of the wide abaucin state reveals non-equivalent central ligands, whereas C2 processing of the same particles averages this asymmetry; the two peripheral ligands form a stable inhibitory core, while the central sites are conditionally occupied in the expanded cavity. Abaucin inhibits ATPase activity and LolA-mediated transfer from substrate-associated LolDF, supporting a unified mechanism in which substrate-induced asymmetry organizes productive handover and its conformational plasticity is redirected during inhibition.

molecular biology↗

Virtual-cell verification enables self-auditing AI discovery for immune rejuvenation

Artificial-intelligence agents propose drug-discovery hypotheses faster than experiments can test them, yet their conclusions are rarely verified, against the underlying biology, the predicted perturbation, or the agent's own scoring logic. We close this verification gap with an agentic framework built on three verifiers. First, PACE, a phenotype verifier, resolves immune aging into ten directionally scored, cell-type-resolved gene-set modules, selected for cross-cohort stability across four PBMC cohorts, and outperforms five established aging clocks in an independent in-house aging cohort of 434 elderly donors. Second, CellQ, a virtual-cell verifier built with multi-modal LLM, compresses each single-cell transcriptome into eight discrete tokens aligned to a language model's vocabulary through residual vector quantization; it attains state-of-the-art perturbation prediction and uniquely resolves the weak, module-level shifts that differential-expression recovery misses. Third, an Analyzer-Planner-Auditor agent verifies its own scoring logic: screening 110 compounds in primary human PBMCs, it found aged-down modules more reversible than aged-up modules and revised its objective from an equal-weight mean to a balance-constrained minimum, a self-correction that generalized to an independent 13-compound T-cell assay. By verifying its predictions and its own objective against experiment, the framework points beyond hypothesis-generating AI toward self-correcting AI scientists whose objectives could continuously evolve.

bioinformatics↗

Individual-tree phenology reveals climate-dependent responses to urban thermal heterogeneity across U.S. cities

Rapid urbanization is altering the seasonal life cycles, or phenology, of urban trees. Diverse species composition and heterogeneous urban thermal environments can generate pronounced phenological variation within cities, yet such fine-scale seasonality remains poorly understood. This limits the ability to anticipate localized ecosystem services and disservices, including canopy cooling and pollen exposure. Here, we analyzed individual-tree phenology and their response to temperature across 76 cities in the contiguous United States by integrating municipal street-tree inventories, PlanetScope satellite time series, and 1-km near-surface urban air-temperature data. We quantified intra-city and cross-city phenological variation, estimated species-level associations between phenology and fine-scale urban temperature, and tested whether these associations vary with regional climatic context. Intra-city phenological variation rivaled cross-city variation for 33.3% of species in spring and 53.7% in fall. Temperature-phenology associations were widespread: warmer local urban environments were associated with earlier spring onset in 51.5% of cases and delayed fall senescence in 66.5%, with approximately two-thirds of these responses cascading to longer growing seasons. These associations varied with regional climate, generally showing stronger spring advancement and fall delay in cooler and wetter cities, but weaker or reversed responses in hotter or drier cities. Together, these results suggest that urban tree phenology is shaped by interactions among fine-scale urban temperature, species identity, and regional climate. Accounting for this heterogeneity can improve predictions of urban forest function and inform climate-resilient species selection and management. Plain Language SummaryStreet trees within the same city do not all leaf out in spring or lose their leaves in fall at the same time. This seasonal timing, called phenology, affects services such as shade and cooling, as well as disservices such as pollen exposure. We studied individual tree phenology and their temperature response in 76 U.S. cities using street-tree records, satellite observations, and local air-temperature data. We asked how much phenology varies within cities, how it responds to neighborhood-scale temperature differences, and whether these responses depend on regional climate. Variation within a city was often as large as variation among cities, especially in fall. Trees in warmer parts of cities generally leafed out earlier and lost their leaves later, often extending the growing season. However, these responses were stronger in cooler and wetter cities and weaker or sometimes reversed in hotter or drier cities. These findings show that urban tree seasonality depends on local temperature, species identity, and regional climate, which should be considered when selecting and managing trees for future cities. Key PointsO_LISubstantial within-city phenological variation is not captured by city-level averages. C_LIO_LIFine-scale temperature shaped phenology and growing-season length, but responses varied across species, cities, and phases. C_LIO_LITemperature sensitivity depended on regional climate, weakening or reversing in hotter or drier cities. C_LI

ecology↗

Viral rewiring of DDR signaling activates a pro-survival network that drives chemotherapy resistance

Radiation and chemotherapy rely on an intact DNA damage response (DDR) to halt cell-cycle progression and eliminate damaged cells, yet many tumors evade these outcomes and develop resistance. Adenoviruses remodel host signaling networks in ways that mirror tumor evolution, providing a powerful system to dissect how DDR pathways are subverted. Here, we identify two scenarios in which the central DDR kinases ATM and ATR are reprogrammed from enforcing CHK1/CHK2-dependent checkpoint arrest to activating a NEMO-NF-{kappa}B survival pathway. This rewiring induces transcriptional programs associated with stress tolerance, anti-apoptotic signaling, and chemoresistance, and promotes the accumulation of cells with abnormal DNA content. These findings reveal a previously unrecognized mode of DDR plasticity that generates a pro-survival state reminiscent of early tumor evolution and suggest how ATM- and ATR-dependent pathways can be co-opted to promote therapeutic resistance.

molecular biology↗

RVQ-Alpha: Bridging Single-Cell Transcriptomics and Large Language Models via Discrete Tokenization and Verifiable Reinforcement Learning

Single-cell RNA sequencing yields continuous expression profiles, whereas large language models operate over discrete autoregressive sequences, leaving no shared computational interface for language-model reasoning over cell states. Existing approaches either keep cellular information outside the LLM vocabulary, consume context per listed gene, or learn reconstruction codes without gene-level grounding. We introduce RVQ-Alpha, which systematically adapts four stages of LLM training (tokenization, supervised fine-tuning, reinforcement learning, and distillation) to single-cell analysis. Multi-codebook Residual Vector Quantization (RVQ) lexicalizes each profile into a compact, hierarchical cellular alphabet in the models native token stream, while a paired decoder reconstructs the corresponding expression profile. Evidence-First supervision grounds these symbols in named genes and expression-linked evidence; Fact-Aware RLVR then penalizes contradictory claims to support auditable reasoning. Task-specific RLVR yields strong experts, but a single Mixed policy underperforms them across all four task families. To recover specialist competence in a unified model, we adopt Multi-Teacher On-Policy Distillation (MOPD), which consolidates these experts into one All-in-One checkpoint without retaining a separate policy for each task. On the CAPSTONE benchmark, a four-task suite with explicit biological shifts and deterministic ontology-aware graders, the unified checkpoint improves over Mixed on all 12 metrics and remains within 0.005 of the task-routed specialist reference on every primary metric. Overall, RVQ-Alpha provides a unified pipeline for grounded, auditable multi-task single-cell analysis.

bioinformatics↗

Dysregulation of "Don't Eat Me" Signaling-Related Genes in Sepsis: A Targeted Transcriptomic Analysis

Sepsis remains a life-threatening condition with limited therapeutic options targeting immune dysregulation. The CD47-SIRP "dont eat me" signaling axis, well characterized in tumor immune evasion, has not been systematically investigated in the context of sepsis. In this study, we performed a targeted transcriptomic analysis of phagocytosis- and "dont eat me" -related genes using the GSE228541 dataset (14 sepsis patients, 15 healthy controls). We identified 8 significantly differentially expressed genes within the curated gene panel. Key changes included downregulation of CD47 (logFC = -0.88, FDR = 5.6 x 10-4) and marked upregulation of PRTN3 (logFC = 2.68, FDR = 6.1 x 10-4). Gene Ontology (GO) enrichment demonstrated prominent alterations in pathways including negative regulation of phagocytosis (GO:0050765, FDR = 7.6 x 10-22), endocytosis, and inflammatory responses. Co-expression network analysis identified SNX3, DYSF, and PLSCR1 as hub genes within this regulatory module. Immune infiltration analysis showed increased M1 macrophage polarization and neutrophil activation in sepsis. Using LASSO regression, we constructed a 6-gene diagnostic signature (PLSCR1, SNX3, DYSF, PRTN3, CSK, CD47) that discriminated sepsis from controls with good performance (AUC = 0.933 in the test subset). Downregulation of CD47 suggests impaired "self" recognition, which may contribute to aberrant phagocytosis during sepsis. Elevated PRTN3 is consistent with neutrophil activation and extracellular trap formation, linking innate immune activation to tissue injury. This targeted transcriptomic analysis reveals coordinated transcriptional reprogramming of phagocytosis-regulatory genes in sepsis and supports the CD47-SIRP axis as a candidate therapeutic target for further investigation.

bioinformatics↗

Vagus Nerve Stimulation Ameliorates Epilepsy via a Gut Microbiota-Butyrate-Vagus Nerve-Brain Axis

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy, yet its mechanism remains partially understood. Here, through an integrated clinical-translational approach, we demonstrate that VNS modulates the gut microbiome and alter the level of butyrate to reduce seizure susceptibility via vagus nerve-dependent signaling. In a longitudinal cohort of epilepsy patients, VNS enriched short-chain fatty acid-producing bacteria, including Akkermansia muciniphila, Prevotella, Alistipes, and Odoribacter. Among clinical responders, fecal butyrate levels decreased concomitantly with an increase in plasma butyrate concentrations. Fecal microbiota transplantation from post-VNS patients into mice reduced seizure severity and improved gut barrier integrity. In a murine model of epilepsy, VNS similarly increased the abundance of Akkermansia and plasma butyrate concentrations, decreased fecal butyrate levels, and abolished its antiseizure effects upon vagotomy. Either colonization with Akkermansia muciniphila or exogenous butyrate supplementation was sufficient to reduce seizures and anxiety-like behavior, effects that also required intact vagal signaling. Our findings define a microbiota-butyrate-vagal pathway essential for the therapeutic effects of VNS, highlighting the gut-brain axis as a target for epilepsy treatment. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/707138v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@8243e6org.highwire.dtl.DTLVardef@37f0e6org.highwire.dtl.DTLVardef@a8b321org.highwire.dtl.DTLVardef@1887342_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIVagus nerve stimulation (VNS) remodels the gut microbiota and alter the level of butyrate. C_LIO_LIVNS enriches short-chain fatty acids-producing bacteria, specifically Akkermansia muciniphila, in both humans and mice. C_LIO_LITransplantation of VNS-conditioned microbiota confers seizure protection and restores gut barrier integrity. C_LIO_LIAkkermansia muciniphila or exogenous butyrate is sufficient to reduce seizures via a vagus nerve-dependent pathway. C_LI

neuroscience↗

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↗

BaCas12a3 represents a new subtype of type V CRISPR effector with collateral activity toward tRNA

The CRISPR-Cas12 family encompasses diverse RNA-guided nucleases with both DNA-targeting and RNA-targeting subtypes. They can trigger antiviral activities mainly through either direct elimination invading nucleic acids, or activating broad collateral cleavage to induce abortive infection. Here, we report a novel type V CRISPR effector BaCas12a3 that causes growth inhibition through a unique tRNA-cleavage mechanism. Plasmid interference assays indicated that BaCas12a3 inhibits host growth arrest without invoking the DNA damage response, suggesting that the immune responses may not involve double strand breaks of DNA. Indeed, biochemical characterization of the BaCas12a3-crRNA ribonucleoprotein (RNP) unraveled that the effector is an RNA-activating nuclease that cleaves 3' terminus of tRNAs. Cryo-EM structures of BaCas12a3 reveal a conserved bilobed architecture featuring a unique nucleic acid-loading (NL) domain adjacent to the RuvC catalytic center. Structural and mutagenesis analyses show that the NL domain, together with a zinc ribbon domain, form a gated substrate groove. Target RNA binding induces conformational changes that open this groove and expose the RuvC active site, enabling specific tRNA cleavage while preventing other non-specific degradation. Our findings identified the NL domain aside the RuvC active site responsible for the tRNA recognition in BaCas12a3, expanding the functional diversity of CRISPR immunity.

molecular biology↗

APOL1 G1 and G2 risk alleles modulate severity of diet-induced obesity in a transgenic mouse model

APOL1 G1 and G2 risk alleles are associated with an increased risk of chronic kidney disease. However, a causal relationship between these alleles and cardiometabolic traits has not been experimentally validated. To address this gap, we placed transgenic APOL1 G0, G1, and G2 FVB/NJ mice on a high-fat diet and analyzed them for weight gain as well as obesity-related cardiometabolic phenotypes. To test whether APOL1 risk alleles modulate the inflammatory basis of obesity, we also exposed bone marrow derived macrophages from these mice to pro-inflammatory, pro-hypertensive, and dyslipidemic conditions. APOL1 high-risk allele female mice gained fat mass more readily than their low-risk female counterparts, while APOL1 high-risk male mice gained fat mass less readily than low-risk males. A parallel sex difference was seen in expression of higher levels of Abca1, Hmox1, and Srebf1 in lipid-loaded female bone-marrow derived macrophages expressing G1 and G2 APOL1, along with minor differences in cardiac function. However, this finding occurred independently of hypertension and insulin resistance, and with only minor albuminuria. Thus, our results highlight the importance of sex as a biological variable in future APOL1 experiments.

genomics↗

A scalable screening platform for discovering predominant miRNA target genes and druggable siRNA sequences

Programmable RNA-targeting systems, including RNA interference (RNAi) and CRISPR-Cas13, are transformative tools for research and therapeutics. However, a lack of high-resolution comparative data obscures whether these mechanistically distinct platforms share fundamental rules for target-site selection. To address this, we developed shRNAone, an engineered scaffold that eliminates processing heterogeneity to guarantee guide biogenesis at single-nucleotide precision. Deploying this platform to systematically decouple microRNA pairing rules in cellulo, we demonstrate that while seed pairing drives primary target recognition, 3'-supplementary pairing is strictly essential for specific transcript repression. Furthermore, single-nucleotide shRNAone tiling screens accurately predict siRNA efficacy and reveal clustered, highly permissive silencing hotspots localized within 3' UTRs. By mapping CasRx and PspCas13b silencing landscapes across the identical mRNA, we show that these hotspots represent intrinsic structural vulnerabilities governed by local RNA accessibility. However, while shRNAone and CasRx activity is largely restricted to the 3' UTR, PspCas13b efficiently targets the coding sequence, highlighting its unique capacity to overcome ribosome occupancy. Together, these high-resolution profiles define the shared and distinct structural barriers governing diverse RNA-targeting systems and provide a rationally designed, transcriptome-wide guide resource for PspCas13b applications.

molecular biology↗

Redefining Parkinson's Disease by Dysregulated Genetic Networks in Distinct Cell Types

Parkinsons disease (PD) is classically linked to dopaminergic neuron loss, but emerging evidence suggests broader cellular involvement. Here we show that PD risk variants converge on distinct molecular networks across specific brain cell types, enabling stratification of patients into six subgroups: dopaminergic, oligodendrocyte progenitor cells (O), excitatory (E), dopaminergic/excitatory, dopaminergic/oligodendrocyte and other. While all subgroups exhibit motor symptoms, the E-group individuals also display more severe non-motor symptoms, including dementia, hyposmia, and REM sleep behavior disorder. The O-group individuals exhibit reduced myelin integrity, as demonstrated by diffusion tensor imaging, implicating NRG6 (formerly C1orf56), a previously uncharacterized high-risk PD gene. We show that NRG6 encodes a conserved epidermal growth factor-like domain structurally and functionally analogous to neuregulin-1, which is critical for oligodendrocyte development and myelination. These findings redefine the cellular architecture of PD vulnerability and identify neuregulin-like signaling in oligodendrocytes as a potential contributor to non-motor symptoms.

neuroscience↗

Translating clinical gene sequencing into a foundational representation of tumor subtype

While gene sequencing is routine in cancer care, translating sequences into treatment decisions remains a challenge. Here we introduce MutationProjector, an AI foundation model that transforms tumor mutation profiles into a compact representation of cancer subtype, with broad implications for diagnosis and therapy. MutationProjector is pre-trained by integrating genomic alterations from >30,000 tumors with extensive molecular knowledge, yielding a model that accurately reconstructs held-out genetic profiles (demonstrating strong generalization) and determines subtype representations from altered molecular pathways (enabling model interpretability). We evaluate MutationProjector in independent tasks related to prediction of immunotherapy response, prediction of chemotherapy response, and classification of metastasis, recording leading performance in all areas. Each task identifies key biomarkers of interest, including KMT2A and KRAS-STK11 alterations which govern immunotherapy response.

systems biology↗

Crosslinking of Lipid Nanoparticles Enhances the Delivery Efficiency and Efficacy of mRNA Vaccines

Lipid nanoparticles (LNPs) have enabled the effective delivery of RNA therapeutics and mRNA vaccines. However, their broader applications are limited by the suboptimal stability and endosomal escape efficiency. Here, we present an easy-to-adopt post-assembly crosslinking approach to enhance the structural and functional stability of mRNA LNPs. By leveraging a series of cholesterol derivatives and crosslinking methods, we induce crosslinks of the lipid components following mRNA LNP assembly to form the crosslinked LNPs (cLNPs). We systematically evaluated crosslinking parameters and identified optimal conditions that enhance both the physical stability and transfection efficiency of cLNPs. Our findings demonstrate that cLNPs exhibit improved structural integrity under storage and lyophilization conditions, as well as increased extracellular stability and endosomal escape efficiency, resulting in improved performance of mRNA LNPs both in vitro and in vivo. This crosslinking strategy represents a critical advance in LNP engineering, enabling more resilient LNPs and broadening the applicability of LNP-based therapies for gene therapy and vaccine delivery. Our work lays the foundation for developing next-generation LNPs with superior stability and delivery efficiency, broadening the impact of RNA therapeutics and vaccines.

bioengineering↗

Immunomodulatory effect of HLA-G Overexpressed Mesenchymal Stromal Cell in Cell-based Therapy for Myocardial Infarction

BackgroundOur previous study demonstrated that intravenous administration of mesenchymal stromal cells (MSCs) significantly increased local cell engraftment and improved heart function. We sought to investigate whether HLA-G1 overexpressed MSCs could further increase local transplanted cells engraftment and improve heart function. Methods and ResultsMice were randomized to receive intravenous administration of saline, human umbilical cord blood derived MSCs (hUCB-MSCs) 7 days prior to acute myocardial infarction (AMI), induced by ligation of the left anterior descending coronary artery. Then, intramyocardial transplantation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) was performed 30 minutes following AMI. Echocardiographic assessment was performed to assess heart function. In-vivo fluorescent imaging analysis were used to analyze cell engraftment. Flow cytometry of splenic regulatory T cells (Tregs) and natural killer (NK) cells was conducted to evaluate the immunomodulatory effect. Our result showed that systemic intravenous administration of hUCB-MSCs significantly increased systemic Tregs, decreased systemic NK cells, increased cell engraftment of intramyocardial transplanted hiPSC-CMs, culminating in improvement of heart function. Our in-vitro study showed that HLA-G1 overexpressed hUCB-MSCs modulated immune response by decreasing pro-inflammatory cytokines. ConclusionsSystemic intravenous administration of HLA-G1 overexpressed hUCB-MSCs modulated immune response and enhanced the survival of local transplanted hiPSC-CMs to improve heart function following AMI.

cell biology↗

Structural Basis for Cas9-Directed Spacer Acquisition in Type II-A CRISPR-Cas Systems

CRISPR-Cas systems confer prokaryotic adaptive immunity by integrating foreign DNA (prespacers) into host arrays. Type II-A systems employ Cas9 for protospacer adjacent motif (PAM) recognition and coordinate with Csn2 and the Cas1-Cas2 integrase during spacer acquisition, yet their structural basis remains unresolved. Here, we report cryo-EM structures of the Enterococcus faecalis Cas9-Csn2-Cas1-Cas2 supercomplex in apo and DNA-bound states. The apo-state structure (Cas92-Csn28-Cas18-Cas24) adopts a resting conformation, with Cas9 locked in a nuclease-inactive state and Cas1-Cas2 sterically blocked from prespacer loading. Upon DNA engagement, Cas9 undergoes a conformational transition, forming a prespacer catching complex that threads the DNA through Csn2s central channel. This architecture enables Cas9 to interrogate the PAM sequence while sliding along the DNA, with Cas9 and Csn2 jointly define a 30-bp DNA segment which matches the prespacer length. Subsequent dissociation of Cas9 triggers a structural reconfiguration of the Csn2-Cas1-Cas2 assembly. The PAM-proximal DNA becomes accessible, and Cas1-Cas2 relocates to bind to the exposed DNA, enabling further prespacer processing and directional integration. These findings reveal how Cas9 collaborates with Csn2 and Cas1-Cas2 to couple PAM recognition with prespacer selection, resolving the dynamic structural transitions that ensure fidelity during type II-A CRISPR adaptation.

molecular biology↗

The adenovirus E4orf1 protein initiates a feedback loop involving insulin and growth factor receptors, AKT, and NF-κB, leading to abnormal DNA content in infected cells

Abnormal DNA levels, such as aneuploidy and polyploidy, can indicate cellular transformation and cancer; however, the mechanisms remain poorly understood. All tumor viruses inherently cause abnormal DNA content in cells due to their oncogenes. During infections, adenovirus (Ad) oncogenes--early region 1A (E1A), early region 4 open reading frame 3 (E4orf3), and E4 open reading frame 1 (E4orf1)--promote the abnormal buildup of cellular DNA. Previous studies have described how E1A and E4orf3 lead infected cells to accumulate abnormal DNA content; however, the role of E4orf1 remains speculative. In this study, we generated cells that express E4orf1 to investigate its role in abnormal DNA content. The E4orf1-expressing cells initially exhibited no increase in DNA content compared to the control group. However, after Ad infection, they displayed higher ploidy levels. To detail how E4orf1 influences ploidy levels in Ad-infected cells, we employed pharmacological agents that target E4orf1 signaling. Our results indicate that E4orf1 enhances signaling from insulin and growth factor receptors to AKT and NF-{kappa}B, creating a feedback loop that elevates levels of cellular DNA in Ad-infected cells. Author SummaryThe early region 4 open reading frame 1 of adenovirus (E4orf1) is recognized for its ability to initiate signals that convert normal cells into cancerous ones. In the initial stages of cancer, cells exhibit DNA content that exceeds the typical levels seen during the G2 and M phases of the cell cycle. This study demonstrates that E4orf1 can trigger a feedback loop involving EGFR, INSR, IGF1R, AKT, and NF-kB, which is both dependent on and independent of PI3 kinase and leads to the accumulation of abnormal DNA content.

cancer biology↗

Infectome Analysis of Small Mammals in Southern China Reveals Ecological Associations and Emerging Threats from Diverse Pathogens

Small mammals harbor a diverse array of zoonotic pathogens. To date, however, metagenomic surveys of these species have primarily focused on viral diversity, with limited attention paid to bacteria and eukaryotic pathogens. Additionally, the ecological determinants of pathogen diversity within these mammals have not been systematically examined. Herein, we employed a metatranscriptomics approach to survey the pathogen infectome of 2,408 individual samples, representing lung, liver, and gut tissues from 858 animals collected throughout Guangdong province, China, with a study design that accounted for host species, tissue, season, and geographic location. We identified 76 pathogen species, including 29 RNA viruses, 12 DNA viruses, 5 bacteria, and 30 eukaryotic pathogens, 33 of which were newly discovered. Tissue distribution analysis revealed distinct organotropisms, suggesting varied transmission routes, while host distribution analysis showed that each animal carried an average of one pathogen, with 10 pathogens widely distributed among mammalian orders. Our characterization of the geographic and seasonal patterns revealed that pathogen richness was primarily influenced by region, host species, and season, while pathogen composition was largely shaped by host genetic distance. Collectively, these data provide the first comprehensive insight into the dynamics of the pathogen infectome in these key mammalian disease reservoirs, highlighting the major factors driving pathogen diversity and transmission.

microbiology↗