Biology subjects

Zhou, M.

Publications and source records attributed to Zhou, M..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Targeting the host factor HGS-viral membrane protein interaction in coronavirus infection

While current antivirals primarily target viral proteins, host-directed strategies remain underexplored. Here, we performed a genome-wide CRISPRi screening to identify the host protein, Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate (HGS), as essential for the pan-coronaviruses infection both in vitro and in vivo. Mechanistically, HGS directly interacts with the viral membrane (M) protein, facilitating its trafficking to the ER-Golgi intermediate compartment (ERGIC) for virion assembly. Conversely, HGS deficiency caused M retention in the ER, blocking assembly. Leveraging this interaction, we designed M-derived peptides and screened over 5,000 FDA-approved drugs, identifying riboflavin tetrabutyrate (RTB). Both the peptides and RTB bind HGS and disrupt its interaction with the M protein, leading to M retention in the ER and subsequent blockade of virion assembly. These agents demonstrated broad anti-pan-coronavirus activity in vitro and in vivo. Collectively, our findings establish HGS as a druggable host target and identify RTB as a promising broad-spectrum antiviral candidate.

microbiology↗

bioRxiv2025

CTDP: Identifying cell types associated with disease phenotypes using scRNA-seq data

Single-cell RNA sequencing enables transcriptome-wide analysis at single-cell resolution, offering unprecedented insights into cellular heterogeneity across biological conditions. However, accurately comparing transcriptomic distributions of cells from distinct biological states, such as healthy versus diseased individuals, remains challenging. To address this, we developed CTDP, a robust and interpretable computational framework that identifies disease phenotype-associated cell types of interest by integrating Lasso-regularized logistic regression with permutation testing. Through comprehensive evaluations on both simulated and real-world datasets, including melanoma immunotherapy, COVID-19 severity, and liver cirrhosis, CTDP consistently outperformed existing methods such as DA-seq, scDist, and PENCIL in both accuracy and robustness. In melanoma, CTDP uncovered immune-responsive clusters and revealed transcriptional regulators like PTPRC, CREM, and JUNB linked to immunotherapy efficacy. In COVID-19, it identified critical severity-associated cell types, such as B cells, NK cells, epithelial cells, and macrophages, which contribute to dysregulated immune responses and inflammation in severe cases. These results highlight CTDPs power in uncovering disease-relevant cell populations and its potential to advance precision medicine through single-cell analysis.

bioinformatics↗

bioRxiv2025

An ultra-long acting insulin enables glucose-synchronised release

Delayed and weak glucose-responsive kinetics, coupled with short plasma exposure and complicated formulation, remain major obstacles to the clinical translation of glucose-responsive insulin formulations. Here we report a rapidly absorbable, ultra-long acting, and glucose-responsive insulin analogue via engineering recombinant human insulin with two phenylboronic acids. The insulin analogue has a long circulating half-life (t1/2{beta} [~]150 h) due to its unique, unprecedented, glucose-responsive binding to blood circulation-associated proteins. This interaction drives the formation of a unique systemic reservoir that allows synchronised dynamic response in insulin levels to glucose fluctuations. In type 1 diabetic mice and minipigs, a single subcutaneous dose can maintain normoglycaemia for over one week (47.5-fold compared to insulin glargine). After the last injection of four consecutive weekly administrations in mice, the glucose-lowering effect can last 800 hours. Administering this glucose-responsive insulin analogue with a fully automated insulin delivery system can leverage dual closed loops and achieve a glucose time in range of over 85% and a coefficient of variation of approximately 30%, better than the recommended targets for human therapy. Importantly, no toxicity was identified in the study.

bioengineering↗

bioRxiv2025

Interface-Sensitive Epi-Coherent Anti-Stokes Raman Scattering Microscopy for Imaging Cell Adhesion Dynamics

Studying cell adhesion dynamics is critical to understand how cells interact with the extracellular matrix and how they migrate. Conventional microscopy techniques for interfacial studies either lack chemical information or require fluorescence labeling. We found that homodyne epi-coherent anti-Stokes Raman scattering (epi-CARS) microscopy, when focused as interfaces, has intrinsic interfacial selectivity. The interference of the back-reflected nonresonant signals amplifies the contrast of cell adhesion areas, generating a distinctive negative contrast at attachment areas, which reflects the distance between the cell membrane and the substrate with tens of nanometers precision. The Epi-CARS configuration also provides high contrasts for cellular lipid droplets when applied in the inverted microscope configuration. Furthermore, by incorporating a pinhole into our confocal epi-CARS system, we can effectively reject out-of-focus reflections that degrade epi-CARS image quality, allowing us to amplify adhesion and lipid droplet contrasts for complex samples, such as cells. We applied this method to study cell-substrate adhesion dynamics of mitotic cells, revealing adhesion site splitting during mitosis and their outward development during postmitotic spreading. Furthermore, we found that after mitosis, the leading edges exhibited homogeneous adhesion regions with thicker water layers, whereas the retracting edges showed heterogeneous adhesion patterns with thinner layers at the contact sites.

biochemistry↗

bioRxiv2025

PHYTOCHROME INTERACTING FACTOR 7 moderates the activity and the cytosolic-nuclear shuttling of PHYTOCHROME A

In nature, plants perceive and respond to complex vegetative environments through the phytochrome (phy) photoreceptor-signaling system. The canopy adaptation strategy, elicited by phyA, together with the shade avoidance syndrome, regulated by phyB, enables plants to adapt to diverse forms of vegetation shade. The phyA High Irradiance Response (HIR) mode, which involves photocycle-coupled nuclear shuttling, is essential for sensing sustained far-red rich conditions typical of canopy or occlusive shade. Our research identifies PHYTOCHROME INTERACTION FACTOR 7 (PIF7) as a key regulator of phyA function. We show that PIF7ox effectively suppresses phyA action. Under persistent shade, PIF7 and phyA both accumulate and interact within nuclear photobodies, with binding mediated by the C-terminal domain of PIF7 and the PAS-PAS domain of phyA. PIF7 also interacts with FHY1 and FHL transport facilitators, thereby interfering with phyA cytosolic-nuclear shuttling. This coordinated molecular targeting by PIF7 constitutes an effective strategy for modulating phyA function under shaded conditions.

plant biology↗

bioRxiv2025

JMJD1B-mediated FEN1 demethylation allows timely switching of Okazaki fragment maturation core enzymes to avoid mutagenic flap ligation by PARP1-LIG3

Efficient and faithful Okazaki fragment maturation (OFM) depends on the PCNA-coordinated actions of core enzymes Pol{delta}, FEN1, and LIG1. We demonstrate that Pol{delta}, FEN1, and LIG1 sequentially but not simultaneously bind to PCNA in mammalian cells. The association of FEN1 with PCNA, which lies at the center of this orderly program, is mediated by FEN1 R192 methylation, which is also crucial for preventing premature loading of LIG1. Conversely, FEN1 demethylation by the recently identified arginine demethylase JMJD1B promotes FEN1 dissociation from PCNA and LIG1 recruitment. Disruption of the sequential PCNA binding program in R192Q or Jmjd1b-/- cells results in unprocessed 5 flaps that prevent OFM and induction of PARP1-dependent recruitment of LIG3, which has flap ligation activity to join incompletely processed OFs. This alternative OFM process supports cell survival but causes duplications and other DNA mutations. Our findings define fundamental and alternative DNA replication processes underlying mutagenesis and cell survival. HighlightsO_LIThe core enzymes involved in Okazaki fragment maturation (OFM), DNA polymerase {delta} (Pol{delta}), flap endonuclease 1 (FEN1), and ligase 1 (LIG1), sequentially bind to the scaffold protein PCNA for their concerted actions C_LIO_LIFEN1 R192 methylation enables FEN1 binding to PCNA; JMJD1B-mediated FEN1 arginine demethylation provokes FEN1 exit from PCNA and LIG1 recruitment C_LIO_LIFEN1 R192Q mutation and JMJD1B deficiency oppositely alter dynamic PCNA interactions with FEN1 and LIG1 and result in distinct OFM DNA intermediate structures C_LIO_LIActivation of PARP1 at replication forks due to disruption of the sequential PCNA binding program induces LIG3-mediated alternative mutagenic 5 flap ligation for survival. C_LI

cell biology↗

bioRxiv2025

Sarbecovirus Rc-o319 S-Protein Structures Reveal Highly Specialized Adaptation to Rhinolophus cornutus ACE2

Bat sarbecoviruses often exhibit species-dependent ACE2 specificity. Understanding the determinants of receptor specificity enables better assessment of the cross-species transmission potential of sarbecoviruses. Here, we characterize the S-protein of Rc-o319, a sarbecovirus identified in Japanese Rhinolophus cornutus bats. Featuring an unusual 9-amino-acid deletion within its receptor binding motif (RBM), Rc-o319 S-protein utilizes its cognate R. cornutus ACE2 (bACE2R.cor) but not human ACE2 (hACE2), demonstrating highly restricted receptor specificity. Cryo-EM structures reveal two locked prefusion conformations of the Rc-o319 S-trimer and define a novel type-1b receptor-binding domain (RBD), featuring a distinct beta-loop (BL) within the RBM due to the RBM-deletion. The Rc-o319-RBD:bACE2R.cor complex structure reveals unique interactions mediated by the specialized BL and RBM-loop of Rc-o319-RBD and by a bACE2R.corglycan. Structure-guided mutagenesis demonstrates that changes in BL and RBM-loop within the Rc-o319 S-RBD must occur simultaneously to allow medium-to-high-affinity hACE2 binding. Comparative assays further show that the bACE2R.cor receptor supports only a subset of sarbecoviruses, highlighting its restricted sarbecovirus compatibility. Our findings establish the Rc-o319 S-protein as a structurally and functionally specialized adaptation to R. cornutus ACE2 and identify the structural constraints limiting its cross-species transmission potential. Author SummarySARS-related viruses are widely found in horseshoe bats. Some can bind the human ACE2 receptor with variable affinities, whereas others bind only bat ACE2 receptors. Understanding the basis for this difference is critical for assessing spillover risk. We studied the spike protein of a bat sarbecovirus, Rc-o319, isolated from Japanese Rhinolophus cornutus horseshoe bats. Although Rc-o319 is genetically related to SARS-CoV-2, it is unable to bind the human ACE2 receptor. Structural analyses and functional experiments revealed that the Rc-o319 spike protein possesses a distinct receptor-binding motif (RBM). This RBM features a specialized "beta-loop" that replaces the "large-loop" found in human-infecting sarbecoviruses. The beta-loop enables high-affinity binding to its cognate Rhinolophus cornutus bat ACE2 receptor while simultaneously preventing optimal interaction with human ACE2. We further found that acquisition of high affinity for the human ACE2 receptor would require coordinated changes across multiple regions of the RBM, including changing the beta-loop into a large-loop structure. Together, our findings demonstrate that the Rc-o319 spike protein is highly adapted to its cognate bat ACE2 receptor and faces substantial structural constraints that limit its ability to switch to binding human ACE2.

microbiology↗

bioRxiv2025

wspA mutation mediated Pseudomonas aeruginosa rugose small colony variant and its hyper-biofilm

Pseudomonas aeruginosa is a major multidrug-resistant pathogen whose biofilm formation complicates treatment. P. aeruginosa rugose small colony variants (RSCVs), characterized by enhanced biofilm production and resistance, pose significant clinical challenges. However, the formation mechanisms remain unclear in clinical strains. Paired clinical P. aeruginosa isolates AR8023-1 (wild-type) and AR8023-2 (RSCV) were collected from urine samples of a neurosurgery inpatient chronologically. The genome comparison was performed using Breseq, and plasmid complementation was performed to construct complemented strain (AR8023-2RifR::wspAAR8023-1). Then, all the aforementioned strains were examined RSCV phenotype, biofilm formation, and motility, and gene expression differences induced by the wspA mutation were analyzed via transcriptome sequencing, followed by quantification of c-di-GMP. In addition, we assessed antimicrobial susceptibility of the strains under both planktonic and biofilm conditions. The results showed that both AR8023-1 and AR8023-2 were identified as ST3420. AR8023-1 exhibited typical smooth morphology, while AR8023-2 displayed a RSCV phenotype. A single SNP difference was identified between the two strains, characterized by a deletion of glutamine at position 289 (CAG triplet deletion) in the wspA gene of strain AR8023-2. The complement isolates restored wild-type morphology, motility, and biofilm formation. Transcriptomics revealed a significant upregulation of c-di-GMP metabolic genes in RSCVs (P < 0.001), indicating that the WspA{Delta}289Q mutation activates diguanylate cyclase (DGC) activity, thereby elevating c-di-GMP synthesis. Intracellular c-di-GMP levels were significantly higher in RSCVs than those in WT and complement isolates, respectively (P < 0.001). Consequently, biofilm susceptibility testing demonstrated the {beta}-lactams MBIC of RSCVs was [≥]8-512-fold higher than those of WT and complement isolates. This study identifies a clinical WspA{Delta}289Q mutation that elevates c-di-GMP, driving RSCV formation and biofilm-mediated resistance. IMPORTANCEP. aeruginosa is a leading multidrug-resistant pathogen whose biofilm formation capability greatly complicates treatment outcomes. This study identifies a novel clinical mutation in the wspA gene (WspA{Delta}289Q) that drives the emergence of rugose small colony variants (RSCVs), a phenotype linked to heightened biofilm production and antimicrobial resistance. We demonstrate that this mutation upregulates cyclic di-GMP synthesis, leading to increased biofilm formation and markedly reduced susceptibility to {beta}-lactam antibiotics under biofilm conditions. These results provide important insights into the genetic basis of RSCV development in clinical settings and highlight the role of c-di-GMP signaling in biofilm-associated resistance. Our findings underscore the need to target c-di-GMP pathways as a potential strategy for combating persistent P. aeruginosa infections.

microbiology↗

bioRxiv2025

Phenotypic screening converges on CDK9 inhibition as a therapeutic strategy in translocation renal cell carcinoma

Translocation renal cell carcinoma (tRCC) is an aggressive kidney cancer driven by gene fusions of the TFE3 transcription factor. TFE3 is essential in tRCC but dispensable in normal cells, presenting an attractive but pharmacologically challenging therapeutic target. We show that the basic helix-loop-helix (bHLH) domain of TFE3 is crucial for chromatin binding and transcriptional function. Via a phenotypic screen of 25,000 compounds, we identified molecules that either displace or retain chromatin-bound TFE3. BRD6866, a compound trapping TFE3 on chromatin, emerged as a pan-CDK inhibitor. Mechanistically, its inhibition of CDK9 - a key regulator of transcriptional elongation - was linked to impaired TFE3 fusion activity. These effects were recapitulated by the CDK9-selective inhibitor enitociclib, which downregulated TFE3 targets and suppressed tRCC cell growth. Our findings nominate CDK9 inhibition as a therapeutic strategy in tRCC and demonstrate the utility of mechanism-informed phenotypic screening for challenging targets.

cancer biology↗

bioRxiv2025

The Pulmonary Microbial Signatures of Early Stages of Severe Infection in Children

The respiratory tract related diseases are the main causes of death in children. Child pulmonary severe infection is the most important inducement for Respiratory tract related diseases. Therefore, it is necessary to understand the composition of the microbial community and the species correlation in children with severe pulmonary infection. In this study, the bronchoalveolar lavage fluid (BALF), blood and cerebrospinal fluid (CSF) samples of 782 children with severe infection in the early stage were systematically analyzed by amplicon-sequencing technology to reveal the distribution of microbial community and its clinical correlation. Results reveal significantly higher bacterial abundance in BALF than in blood/cerebrospinal fluid, with community structures shaped by tissue microenvironments, geographical disparities, age, and clinical symptoms. Neonatal BALF harbors simplified microbiota dominated by probiotics, while diversity increases with age, showing marked differences between 1-3 and 6-12-year-olds. Sepsis samples exhibit reduced microbial diversity, with Staphylococcus and Moraxella enrichments in the CST-4 cluster. Respiratory symptom progression correlates with microbiota succession from oral colonizers to respiratory pathogens. Third-generation sequencing-derived co-occurrence networks illustrate synergistic interactions among opportunistic pathogens, providing a basis for ecological targeted therapy. This study provides a key basis for breaking through the limitations of traditional diagnosis, establishing a precise diagnosis and treatment system based on third-generation sequencing, and developing ecological targeted treatment strategies.

pathology↗

bioRxiv2025

Etiology and antimicrobial resistance of bovine mastitis pathogens in North-Eastern Zimbabwe: Emerging threats and management gaps

Bovine mastitis, a significant challenge for dairy farming in Zimbabwe, affects milk production, animal health, and economic viability. This study investigated the etiology, prevalence and antimicrobial resistance of mastitis pathogens in dairy farms in the north-eastern regions of Zimbabwe. Of the 256 cows tested, 36.3% showed signs of mastitis, predominantly subclinical (28.1%). Key pathogens isolated included Staphylococcus spp. (34.4%), Streptococcus spp. (26.9%), and Escherichia coli (18.3%). Notably, Candida spp. and Corynebacterium bovis were identified for the first time as mastitis pathogens in Zimbabwe. The detection of Candida spp. underscores the impact of prolonged antibiotic use, which disrupts bacterial flora and promotes fungal infections, while the presence of Corynebacterium bovis highlights hygiene deficiencies in milking practices. Alarmingly, 25% of Staphylococcus isolates were multidrug-resistant (MDR), including methicillin-resistant Staphylococcus aureus (MRSA). Resistance to commonly used antimicrobials such as tetracycline and trimethoprim-sulfamethoxazole was widespread, further complicating treatment options. This study emphasizes the need for improved hygiene practices, routine screening, and antimicrobial stewardship to manage mastitis and curb the spread of resistance.

microbiology↗

bioRxiv2025

SVPG: A pangenome-based structural variant detection approach and rapid augmentation of pangenome graphs with new samples

Breakthrough advances in long-read sequencing technologies have opened unprecedented opportunities to study genetic variations through comprehensive pangenome analysis. However, the availability of structural variant (SV) calling tools that can effectively leverage pangenome information is limited. In addition, efficient construction of pangenome graphs becomes increasingly challenging with acquisition of larger number of samples. In this study, we present SVPG, an approach that leverages haplotype-resolved pangenome reference for accurate SV detection and rapid pangenome graph augmentation from long-read sequencing data. Compared to state-of-the-art SV callers, SVPG maintained superior overall performance across different sequencing technologies and coverages. SVPG also achieved notable improvements in calling rare and individual-specific SVs on both simulated and real somatic datasets. Furthermore, in a benchmark involving 20 samples, SVPG accelerated pangenome graph augmentation by nearly 10-fold compared to traditional augmentation strategies. We believe that this novel SVPG method, has the potential to revolutionize SV detection and serve as an effective and essential tool, offering new possibilities for advancing pangenomic research.

bioinformatics↗

bioRxiv2025

Temporal foundation model unveils ancient HepatitisB virus evolution

Since ancient hepatitis B virus (HBV) sequencing data are scarce and incomplete, the evolutionary dynamics of HBV have long remained enigmatic. This data gap hinders a comprehensive understanding of HBV genetic variations, evolutionary trajectories, and host interactions in different historical periods, preventing insight into its long-standing co-evolutionary relationship with humans. In this study, we developed a sequence-based generative foundational model, ViraChron (Viral Chronology Foundation Model), that integrates multi-scale temporal information to compensate for the lack of ancient HBV data. We confirmed the robustness of our model through sequence identity, phylogenetic, and recombination analyses. ViraChron enabled the identification of fixed mutations specific to HBV genotype A, demonstrating that HBV acquires survival advantages through mutations that are ultimately fixed by natural selection. Our model outperforms the original baseline in terms of sequence completion, achieving significantly higher accuracy. The model significantly reduced data acquisition time from 80 hours to 5.4 minutes per HBV genome, providing reliable, high-quality data for 7 new HBV genomes from specific archeological sites. ViraChron overcomes previous limitations, obtaining high-quality genomic data from samples over ten thousand years old, thereby facilitating a systematic understanding of viral evolution and its biological characteristics.

paleontology↗

bioRxiv2025

An efficient beet severe curly top virus-based VIGS vector in Beta vulgaris

Sugar beet (Beta vulgaris L.) is one of the most important sugar crops worldwide. However, studies on sugar beet gene functions are still lagging compared to other crops due to the lack of an effective genetic manipulation. In this study, we generated an infectious clone of beet sever curly top virus (BSCTV) and engineered it into a VIGS vector. BSCTV-BvPDS can induce strong and persistent bleached PDS-silencing phenotype in 8 tested sugar beet varieties. We further efficiently silenced B. vulgaris MYB1 gene that regulating the betalain pathway in sugar beet by BSCTV-based VIGS system. Finally, we used this system to silence the effector CbNip1 of Cercospora beticola through cross-kingdom RNAi, resulting in reduced disease symptoms in sugar beet plants. Therefore, the BSCTV VIGS system can be used to study sugar beet-pathogen interactions. In summary, we have established an easy and efficiency BSCTV-based VIGS vector in sugar beet. This system will be an attractive tool for functional genomic studies for sugar beet.

plant biology↗

bioRxiv2025

A chimeric Ad5-Envp-VLP vaccine platform confers broad-spectrum immunity against emerging and re-emerging pathogens

Integrating complementary vaccine modalities is essential for combating emerging infectious threats. Here, we developed Ad5-Envp-VLP, a chimeric adenoviral platform synergizing adenoviral delivery efficiency with virus-like particle (VLP) structural mimicry. This system stably produces self-assembling VLPs in suspension HEK293 cultures, exhibiting enhanced immunogenicity over soluble antigens. Following intramuscular immunization, the platform induces early B cell expansion and sustains germinal center reactions, driven by the upregulation of B cell cycle-related genes (Cdc6, Cdc45, Cdc20, Cdc25C, Aurka, Aurkb, and Ccnb1/2) and robust T follicular helper (Tfh) cell differentiation, generating durable neutralizing antibodies against both influenza virus and rabies virus. These effects are conserved across mouse, canine, and feline models. Crucially, integrated flow cytometry and scRNA-seq demonstrate that intranasal delivery recruits and functionally reprograms lung innate immune cells (notably alveolar macrophages and dendritic cells), driving mucosal sIgA secretion and CTL responses. A single nasal dose confers lasting protection against homologous and heterologous influenza A strains. The platform also elicits cross-neutralizing antibodies against SARS-CoV-2 variants. Together, Ad5-Envp-VLP thus establishes a modular vaccine platform for antigenically plastic pathogens by combining in vivo self-assembly with dual pulmonary-muscular delivery. One Sentence SummaryNovel mucosal and systemic vaccine delivers self-assembling particles, triggering strong lung immunity and broad virus protection across species.

immunology↗

bioRxiv2025

Global analysis of membrane protein S-acylation in the model plant Arabidopsis thaliana

Protein S-acylation is the addition of fatty acids to the cysteine residues in a protein, catalyzed by protein S-acyltransferases (PATs). Despite extensive research on protein S-acylation in animals, our understanding of this process in plants remains limited. In this study, we sought to characterize the S-acylproteome of membrane proteins in Arabidopsis and identify potential substrates for two important plant immunity-related PATs (PAT5 and PAT9). To achieve this, S-acylated membrane proteins were first enriched via our optimized acyl-biotinyl exchange strategies at both the protein-level and peptide-level. The enriched samples were then analyzed by label-free quantitative liquid chromatography-mass spectrometry. The results from the two enrichment methods demonstrated that they were complementary in identifying S-acylated proteins and S-acylation sites. Using these methods, over 2500 S-acylation sites in more than 2000 putative S-acylated proteins were identified. Proteins involved in vesicle trafficking, plant phosphorylation, immune responses, and signal transduction pathways were significantly enriched. Additionally, certain amino acid patterns surrounding the S-acylation sites were identified. Comparisons of the S-acylproteomes between the wild type and the PAT5 and PAT9 mutants revealed over 100 potential substrates for both S-acyltransferases. The high quality of our data was supported by the significant overlap with the previously reported data and successful experimental verification of selected candidate proteins. Overall, our study revealed a well-represented S-acylproteome for Arabidopsis (especially its membrane proteins) and identified potential substrates for PAT5 and PAT9. These findings will facilitate the functional characterization of S-acylated proteins in plants.

plant biology↗

bioRxiv2025

piR-bmo-796514 Facilitates the Proliferation of Exogenous DNA Virus (Baculovirus) by Targeting the Host E3 Ubiquitin Ligase RNF181

PIWI-interacting RNAs (piRNAs), a class of 23-31 nucleotide non-coding RNAs, are known for silencing transposons and endogenous retroviruses that reside in animal genomes. However, the mechanisms by which host piRNAs affect exogenous viral infections, particularly those by DNA viruses, remain poorly understood. Here, we demonstrate that infection by Bombyx mori nucleopolyhedrovirus (BmNPV), a large DNA virus, induces significant upregulation of silkworm host piR-bmo-796514, which facilitates viral proliferation by suppressing the expression of E3 ubiquitin ligase RNF181. We further reveal that RNF181 exerts antiviral activity through ubiquitin-mediated degradation of Integrin 2b-like, a cellular membrane protein that interacts with viral GP64 protein to mediate BmNPV entry. This study unveils a previously unrecognized regulatory axis connecting host derived piRNAs with exogenous DNA virus infection, providing further mechanistic insights into the modulation of exogenous viral pathogenesis through the reprogramming of the piRNA pathway. Our findings not only advance the understanding of the immune escape mechanism of exogenous viruses but also provide new insights for the development of oligonucleotide antiviral drugs that target proviral piRNAs.

immunology↗

bioRxiv2025

PEARL: Integrative multi-omics classification and omics feature discovery via deep graph learning

Integrating multi-omics data provides valuable insights into biological processes by capturing information across multiple molecular layers, enabling a comprehensive understanding of complex diseases and driving advancements in precision medicine. However, existing computational methods for multi-omics integration face significant challenges, such as low reliability and poor generalizability, due to the high dimensionality and low sample size nature of omics data. To address these challenges, we present PEARL (Pearson-Enhanced spectrAl gRaph convoLutional networks), a novel deep graph learning method for biomedical classification and functional important omics features identification. PEARL leverages a simple yet effective learning architecture to achieve superior and robust performance in high-dimensional, low-sample-size multi-omics settings. Our results demonstrate that PEARL significantly outperforms existing state-of-the-art methods on both synthetic and real biomedical datasets. Furthermore, applied to Alzheimers disease (AD) brain multi-omics data, features prioritized by PEARL lead to functionally important genes that demonstrate significant enrichment in AD-related pathways. These findings highlight PEARLs practical utility in biomedical research and its potential to enhance biological interpretability in multi-omics studies.

bioinformatics↗