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Results for “Comparative transcriptomics”

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PubMed2026

Mechanisms by which carbamoylated high-density lipoprotein (C-HDL) promotes calcific aortic valve disease and exploration of potential targeted therapies.

Calcific aortic valve disease (CAVD) is a progressive fibrocalcific illness for which no effective pharmaceutical treatment exists. This study investigated whether carbamoylated high-density lipoprotein (C-HDL), a defective type of HDL that can develop during inflammation, contributes to CAVD progression and the involved molecular pathways. Male ApoE-/- mice were divided into three groups: CAVD model, cyanate-treated, and inhibitor, and analyzed after 12 weeks. C57BL/6 mice on a regular diet served as blank controls. Serum paraoxonase-1 (PON1), aortic valve calcification, cluster of differentiation 31 (CD31), phosphorylated nuclear factor kappa B p65 (p-p65), NOTCH receptor 1 (NOTCH1), and runt-related transcription factor 2 (RUNX2) were evaluated. In parallel, using RNA sequencing (RNA-seq), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, protein-protein interaction (PPI) network analysis, and quantitative real-time polymerase chain reaction. Cyanate treatment reduced serum PON1 levels, increased von Kossa-positive calcium deposition, and raised CD31, p-p65, NOTCH1, and RUNX2 levels compared with the model group, but Gly partially corrected these effects. Transcriptomic research identified 270 C-HDL-associated differentially expressed genes (DEGs) enriched in pathways associated with inflammatory signaling and NF-κB activity. Five potential hub genes (BIRC6, PIK3R1, ATM, IFIH1, and DDX58) were discovered and verified using qRT-PCR. These data show that C-HDL may accelerate CAVD by disrupting valve endothelial homeostasis and stimulating inflammatory signaling, and they identify potential molecular targets for future functional validation.

bioinformatics↗

PubMed2024

Role of the Pseudomonas plecoglossicida fliL gene in immune response of infected hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

Pseudomonas plecoglossicida, a gram-negative bacterium, is the main pathogen of visceral white-point disease in marine fish, responsible for substantial economic losses in the aquaculture industry. The FliL protein, involved in torque production of the bacterial flagella motor, is essential for the pathogenicity of a variety of bacteria. In the current study, the fliL gene deletion strain (ΔfliL), fliL gene complement strain (C-ΔfliL), and wild-type strain (NZBD9) were compared to explore the influence of the fliL gene on P. plecoglossicida pathogenicity and its role in host immune response. Results showed that fliL gene deletion increased the survival rate (50%) and reduced white spot disease progression in the hybrid groupers. Moreover, compared to the NZBD9 strain, the ΔfliL strain was consistently associated with lower bacterial loads in the grouper spleen, head kidney, liver, and intestine, coupled with reduced tissue damage. Transcriptomic analysis identified 2 238 differentially expressed genes (DEGs) in the spleens of fish infected with the ΔfliL strain compared to the NZBD9 strain. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the DEGs were significantly enriched in seven immune system-associated pathways and three signaling molecule and interaction pathways. Upon infection with the ΔfliL strain, the toll-like receptor (TLR) signaling pathway was activated in the hybrid groupers, leading to the activation of transcription factors (NF-κB and AP1) and cytokines. The expression levels of proinflammatory cytokine-related genes IL-1β, IL-12B, and IL-6 and chemokine-related genes CXCL9, CXCL10, and CCL4 were significantly up-regulated. In conclusion, the fliL gene markedly influenced the pathogenicity of P. plecoglossicida infection in the hybrid groupers. Notably, deletion of fliL gene in P. plecoglossicida induced a robust immune response in the groupers, promoting defense against and elimination of pathogens via an inflammatory response involving multiple cytokines.

Animals↗

PubMed2003

Sputnik: a database platform for comparative plant genomics.

Two million plant ESTs, from 20 different plant species, and totalling more than one 1000 Mbp of DNA sequence, represents a formidable transcriptomic resource. Sputnik uses the potential of this sequence resource to fill some of the information gap in the un-sequenced plant genomes and to serve as the foundation for in silicio comparative plant genomics. The complexity of the individual EST collections has been reduced using optimised EST clustering techniques. Annotation of cluster sequences is performed by exploiting and transferring information from the comprehensive knowledgebase already produced for the completed model plant genome (Arabidopsis thaliana) and by performing additional state of-the-art sequence analyses relevant to today's plant biologist. Functional predictions, comparative analyses and associative annotations for 500 000 plant EST derived peptides make Sputnik (http://mips.gsf.de/proj/sputnik/) a valid platform for contemporary plant genomics.

Databases, Nucleic Acid↗

PubMed2002

Translational machinery of channel catfish: I. A transcriptomic approach to the analysis of 32 40S ribosomal protein genes and their expression.

Ribosomal protein (RP) genes have become widely used as markers for phylogenetic studies and comparative genomics. However, they have not been available for evolutionary studies in fish although teleosts are the largest group of vertebrates with more than 23,000 species. Using a transcriptomic approach, we have cloned and sequenced 32 40S RP complementary DNAs (cDNAs) from channel catfish (Ictalurus punctatus), making them one of the most complete sets of 40S RP gene sequences from a single organism. Most 40S RPs in channel catfish are highly similar to their orthologues in mammalian species, but S19, S21, and S25 are highly divergent. Only one type of cDNA was found for all RP genes except S26 and S27, for which two cDNAs were found in channel catfish. Alternatively spliced transcripts for the S3 and alternatively polyadenylated transcripts for S19 and S21 were found. The 32 40S RP genes are generally highly expressed and together they account for 5.33-11.42% of expression depending on the tissues. Expression levels of the RP genes were highly variable both within a single tissue among different RP genes and among tissues with regard to a single RP gene. Taken together, these data strongly suggest post-transcriptional regulation of RP gene expression, particularly in consideration of the stoichiometry of their representation in ribosomes.

Alternative Splicing↗

PubMed2002

A microarray-assisted screen for potential Hap1 and Rox1 target genes in Saccharomyces cerevisiae.

Saccharomyces cerevisiae adapts to altered oxygen availability by differentially expressing a number of genes. Under aerobic conditions oxygen control of gene expression is exerted through the activator Hap1 and the repressor Rox1. The Hap1 transcription factor senses cellular heme status and increases expression of aerobic genes in response to oxygen. The repression of hypoxic genes under normoxic conditions results from Hap1-mediated activation of ROX1 transcription. To allow the identification of additional Hap1 and Rox1 target genes, genome-wide expression was analysed in aerobically, chemostat-cultivated hap1 and rox1 null mutants. The microarray results show that deletion of HAP1 causes a lower transcript level of 51 genes. Transcription of 40 genes was increased in rox1 mutant cells compared to wild-type cells. Combining these results with our previously described transcriptome data of aerobically and anaerobically grown cells and with computational analysis of the promoters identified 24 genes that are potentially regulated by Hap1, and 38 genes satisfied the criteria of being direct targets of Rox1. In addition, this work provides further evidence that Rox1 controls transcription of anaerobic genes through repression under normoxic conditions.

Anaerobiosis↗

PubMed2026

Experimental evolution of phage K enhances antibacterial activity against USA300 MRSA in lung infection models.

Hypervirulent community-associated MRSA clones such as Staphylococcus aureus (S. aureus) USA300 drive rapidly progressive necrotizing pneumonia with high morbidity and limited therapeutic options. Bacteriophage K (phage K) is a well-characterized lytic phage active against S. aureus, but its efficacy is limited by restricted host range and the emergence of bacterial resistance. Here, we subjected phage K to experimental evolution on S. aureus USA300 to select an adapted variant with enhanced bactericidal properties. Wild-type phage K and the evolved derivative, designated phage KJ25, were compared using growth inhibition assays, time-kill kinetics, genomic differences and transcriptomic analyses of the bacterial response to infection. Efficacy was evaluated in an in vitro A549 lung epithelial cell infection model and ex vivo murine precision-cut lung slices (PCLS). Phage KJ25 exhibited significantly improved killing of USA300, achieving faster bacterial reduction and sustained suppression of regrowth. Genomic analysis identified a function-impairing mutation in gene gp102, encoding a predicted DNA-binding protein implicated in transcriptional regulation. RNA sequencing revealed that KJ25 infection of USA300 induced a slower and less disruptive host transcriptional takeover than wild-type phage K. Importantly, in both A549 cells and PCLS model, phage KJ25 markedly reduced bacterial burden while preserving lung tissue integrity, supporting its therapeutic potential. Collectively, these findings highlight the value of experimental evolution for tailoring therapeutic phages and support phage adaptation as a promising strategy for developing interventions against multidrug-resistant S. aureus.

Methicillin-Resistant Staphylococcus aureus↗

PubMed2026

Influenza A virus co-infection alters Streptococcus pneumoniae gene expression during upper respiratory tract colonization.

Streptococcus pneumoniae (Spn) asymptomatically colonizes the upper respiratory tract (URT), a niche from which it can transmit to another host or cause invasive disease in the same host. The in vivo transcriptional adaptations that Spn undergoes during nasopharyngeal colonization, particularly during influenza A virus (IAV) co-infection, are poorly understood. Here, we leveraged an established infant mouse model of colonization, shedding, and transmission to perform genome-wide transcriptomic profiling of Spn during mono- and during IAV co-infection. Compared with broth-grown controls, pneumococci isolated from the URT exhibited distinct transcriptional programs, with over 200 genes differentially expressed across time points. Genes involved in carbohydrate uptake and metabolism, glycan degradation, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were consistently enriched during colonization, highlighting metabolic adaptation to the nasopharyngeal niche. In contrast, IAV co-infection induced a markedly distinct transcriptional signature, including upregulation of branched-chain amino acid biosynthesis, bacteriocin production, and phosphate acquisition systems. Notably, the pilus islet-1 locus was upregulated during Spn-IAV co-infection. Functional studies demonstrated that while the pilus was dispensable for colonization under mono- and co-infection conditions, it promoted high-shedding events and enhanced inflammatory responses during IAV co-infection. However, reduced inflammation and reduced high-shedding events from pups inoculated with a pilus-deficient mutant did not alter transmission frequency in the infant mouse model. Collectively, our findings define the in vivo transcriptional landscape of Spn during URT colonization and reveal distinct bacterial adaptations during viral co-infection, providing insight into mechanisms that influence pneumococcal persistence, inflammation, and transmission.

RNA-seq↗

PubMed2026

Multinucleated Giant Cells in Human Pancreatic Cancer Are a Distinct Macrophage Population Undergoing a DNA Damage Response and Associated with an Aggressive Tumor Microenvironment.

Macrophages (Mϕ) constitute a dominant and functionally diverse immune population within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), yet how Mϕ heterogeneity contributes to the tumor remains poorly defined. In an institutional cohort of 145 PDAC specimens, we identified a population of multinucleated giant cells (MGC) of Mϕ origin, an entity previously described in chronic inflammation but rarely in cancer. CD68+ MGCs were present in 28% of tumors, enriched in squamous, nonglandular regions, and more frequent after neoadjuvant chemotherapy. By integrating spatial transcriptomics and quantitative imaging, we defined the features of these cells, which, compared with MGCs in nonneoplastic inflammatory lesions, lacked canonical polarization markers (HLA-DR and CD163) and displayed a distinctive transcriptional program characterized by upregulation of the POLR2K, TUBA8, COX5B, and VDAC1 genes, which encode proteins involved in DNA repair, oxidative stress, and MYC signaling. Spatial analyses revealed activation of hypoxia and extracellular matrix-remodeling pathways in MGC-associated niches, and experimental hypoxia promoted MGC formation in vitro. Consistent with these data, we found that in the The Cancer Genome Atlas (TCGA) Pancreatic Adenocarcinoma (PAAD) dataset a Mϕ MGC gene signature was enriched in the squamous PDAC subtype and correlated with poorer overall survival (P = 0.018). Morphometric and immunofluorescence analyses further showed increased 53BP1+Ki67+ nuclei and nuclear atypia in MGCs, indicating ongoing proliferation despite DNA damage. Together, these data identify MGCs of Mϕ origin as an immune cell state shaped by hypoxia and stress signaling, associated with aggressive tumor phenotypes, and potentially exploitable as an immune classifier in PDAC.

Humans↗

PubMed2026

Influenza A Virus Coinfection Alters Streptococcus pneumoniae Gene Expression during Upper Respiratory Tract Colonization.

Streptococcus pneumoniae (Spn) asymptomatically colonizes the upper respiratory tract (URT), a niche from which it can transmit to another host or cause invasive disease in the same host. The in vivo transcriptional adaptations that Spn undergoes during nasopharyngeal colonization, particularly during influenza A virus (IAV) coinfection, are poorly understood. Here, we leveraged an established infant mouse model of colonization, shedding, and transmission to perform genome-wide transcriptomic profiling of Spn during mono- and during IAV co-infection. Compared with broth-grown controls, pneumococci isolated from the URT exhibited distinct transcriptional programs, with over 200 genes differentially expressed across time points. Genes involved in carbohydrate uptake and metabolism, glycan degradation, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were consistently enriched during colonization, highlighting metabolic adaptation to the nasopharyngeal niche. In contrast, IAV coinfection induced a markedly distinct transcriptional signature, including upregulation of branched-chain amino acid biosynthesis, bacteriocin production, and phosphate acquisition systems. Notably, the pilus islet-1 locus was upregulated during Spn-IAV coinfection. Functional studies demonstrated that while the pilus was dispensable for colonization under mono- and coinfection conditions, it promoted high-shedding events and enhanced inflammatory responses during IAV coinfection. However, reduced inflammation and reduced high shedding events from pups inoculated with a pilus-deficient mutant did not alter transmission frequency in the infant mouse model. Collectively, our findings define the in vivo transcriptional landscape of Spn during URT colonization and reveal distinct bacterial adaptations during viral coinfection, providing insight into mechanisms that influence pneumococcal persistence, inflammation, and transmission.

Journal Article↗

PubMed2025

Multi-Omics Analysis of the Potential Mechanisms of Skin Albinism in Edangered Percocypris pingi: Abnormal Ubiquitination and Calcium Signal Inhibition.

Percocypris pingi is an endangered protected fish species in China. Its albino variants exhibit growth retardation and physiological abnormalities. Understanding its albinism mechanism holds significant scientific importance for molecular breeding programs and disease model development. This study integrated transcriptomic and proteomic analyses, combined with histopathological and molecular biological techniques, to systematically compare molecular differences in skin tissues between albino and wild-type P. pingi, with a focus on elucidating the multidimensional regulatory mechanisms underlying skin albinism. Our findings suggest that albinism in P. pingi is synergistically driven by hyperactivation of ubiquitin-mediated proteolysis (which suppressed TYR/TYRP1 enzymatic activity and disrupted the pH homeostasis of melanosomes), and inhibition of calcium signaling (which impeded melanin transport). This discovery provides novel insights into the mechanisms of pigment loss in fish species and offers a valuable reference for molecular breeding of endangered species as well as research on pigmentation-related disorders.

Animals↗

PubMed2026

Integrated Transcriptomic and Proteomic Analysis Elucidates the Mechanisms of Huperzine A Injection Against Cerebral Ischemia/Reperfusion Injury.

BACKGROUND: After recanalization in acute ischemic stroke, cerebral ischemia/reperfusion injury (CI/RI) drives a cascade of pathophysiological events that worsen clinical outcomes, yet effective therapeutic options remain limited. Given the neuroprotective potential of Huperzine A (HupA), the efficacy of HupA injection (HAI, a major clinical formulation of HupA) against CI/RI and its underlying molecular basis warrant investigation. METHODS: In a mouse model of CI/RI, neurological performance, locomotor ability, cerebral infarction, histopathological alterations, and apoptotic neurons were jointly used to assess the anti-CI/RI effect of HAI at two different doses. An integrated transcriptomic and proteomic strategy was adopted to decipher the key anti-CI/RI mechanisms of HAI and then validated experimentally. RESULTS: Compared with vehicle‑treated CI/RI mice, HAI intervention significantly alleviated neurobehavioral deficits, decreased infarct size, mitigated histopathological damage, and suppressed neuronal apoptosis (P < 0.01). Both separate and combined transcriptomic and proteomic analyses highlighted that the complement and coagulation cascades, together with inflammation, were strongly correlated with HAI's beneficial action in preventing CI/RI. Indeed, HAI treatment effectively normalized the dysregulated mRNA and protein levels of pivotal targets within the complement and coagulation cascades, including C3, C5, C9, CFB, MASP2, F7, F10, F12, and SERPINE1, in the damaged cortical tissues of CI/RI mice (P < 0.05). Moreover, this intervention markedly attenuated the abnormally elevated expression of multiple inflammatory mediators, including TLR2, TLR4, TNF-α, IL-1β, IL-6, CCL2, CCL5, CXCL1, ICAM1, S100A9, LCN2, MMP8, and MMP9, at both the mRNA and protein levels (P < 0.01). CONCLUSION: Collectively, our data suggest that HAI may confer efficacy against CI/RI by modulating the complement and coagulation cascades and orchestrating the inflammatory response. Although further investigation is warranted, these preliminary findings provide a foundation for accelerating the clinical translation of HAI as a novel neuroprotectant against CI/RI in ischemic stroke.

Animals↗

PubMed2026

Beyond ion channel dysfunction: Integration of the transcriptome and proteome from patient-specific re-engineered cardiac cells, and population-level QT genome-wide association study reveals broad cellular dysfunction.

BACKGROUND: Congenital long QT syndrome (LQTS) is a cardiac channelopathy with increased risk of cardiac-triggered syncope/seizures, sudden cardiac arrest, and sudden cardiac death. OBJECTIVE: This study aimed to describe the transcriptomic and proteomic profiles in patient-derived inducible pluripotent stem cell-derived cardiomyocyte (iPSC-CM) models of the 3 canonical genotypes of congenital LQTS: LQT1, LQT2, and LQT3 and integrate these omics-level findings with each other and with population/clinical level QT-genome-wide association study (GWAS) data. METHODS: LQT1, LQT2, LQT3 and respective isogenic control iPSC-CMs were cultured, and RNA and protein samples were collected. RNA sequencing and mass spectrometry-enabled proteomic analysis was performed. PrediXcan analysis was performed using QT GWAS summary statistics and transcriptome expression data. Differential gene and protein expression and ingenuity pathway analysis (IPA) was performed comparing each LQT genotype with its respective isogenic control. RESULTS: 1645 differentially expressed genes (DEGs) were identified; 13 were altered in all 3 LQTS genotypes. IPA analysis of DEGs revealed 301 altered pathways; 47 were altered in all LQTS genotypes. Proteomic analysis identified 2561 differentially expressed proteins (DEPs); 30 were altered in all 3 genotypes. IPA analysis of DEPs identified 646 altered pathways. 306 genes/proteins were identified as significantly altered in both the transcriptome and proteome; pathway analysis of these 301 genes identified 201 altered pathways. 7 pathways were altered in all 3 LQTS genotypes in both the transcriptome and proteome. Integration of the population-level PrediXcan results and the cardiomyocyte-derived omics results identified multiple shared pathways. CONCLUSION: Multi-omics analysis of LQTS and integration of omics results with QT GWAS data reveals that primary LQTS-causative ion channel defects precipitate secondary alterations in a wide range of cellular pathways. Our findings suggest more broad molecular level changes throughout the cell. This study lays the foundation for further exploration of broad cellular changes resulting from ion channel disturbances and how they contribute to disease mechanism.

Humans↗

PubMed2025

Genomic and Transcriptomic Landscape of Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma: A Multicenter Study.

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is a rare indolent malignant neoplasm, which occurs almost exclusively in the liver or spleen and may arise from a common EBV-infected mesenchymal cell that differentiates along the follicular or fibroblastic dendritic cell pathway. Despite its rarity, it presents a pressing need for an improved understanding of its genetic underpinnings and potential treatment strategies for recurrent or disseminated cases. To address this, we conducted comprehensive whole-exome sequencing and transcriptome sequencing (mRNA-seq) analyses on 31 and 6 cases of EBV+ IFDCS, respectively, collected from multiple centers in China. We also compared the genetic features of EBV+ IFDCS with those of other EBV-associated malignancies. Our analyses revealed a relatively high somatic mutation rate and widespread copy number variations affecting the major histocompatibility complex-I/II in EBV+ IFDCS. Integrated mutational profiling identified key signaling pathways involved in epigenetic regulation, NF-κB signaling, RTK/RAS/PI(3)K, and the Hippo pathway. Furthermore, we identified several frequently altered genes that could serve as potential therapeutic targets in EBV+ IFDCS. Transcriptomic analysis unveiled significant upregulation of pathways related to virus infection, immune responses, and multiple immune checkpoint genes in EBV+ IFDCS. Comparative analysis demonstrated clear genetic distinctions between EBV+ IFDCS and other EBV-associated tumors. In conclusion, our study provides comprehensive insights into the unique genomic and transcriptomic landscape of EBV+ IFDCS. We have identified multiple genetic alterations that likely contribute to the development and progression of this malignancy. Our results suggest that targeted therapy and immune checkpoint inhibitors may hold promise as potential therapeutic approaches for patients with recurrent or disseminated EBV+ IFDCS.

Humans↗

PubMed2026

Comparative phylogenomics and transcriptional regulatory networks of AQPs, HSPs, and LEA proteins in salt-stressed Portulaca oleracea.

Soil salinization severely threatens global food security, necessitating systematic investigations of halophytes like Portulaca oleracea to decode the molecular mechanisms of environmental resilience. Utilizing an integrated framework of deep learning-based genome annotation (58,817 predicted genes; 96.5% BUSCO completeness), multi-tissue RNA-Seq, phylogenomics, and gene regulatory network (GRN) inference, the synergistic orchestration of 78 aquaporins (AQPs), 525 heat shock proteins (HSPs), and 119 late embryogenesis abundant (LEA) proteins was elucidated. The active transcriptome, encompassing 39,065 expressed loci, revealed a systemic growth-defense trade-off. Tissues displayed distinct adaptive mechanisms: leaves modulated intracellular water balance via specialized AQPs, whereas adult roots maintained proteostasis through robust HSP20/HSP70 induction. Phylogenomic clustering across 154 species demonstrated that salinity tolerance constitutes an evolutionary mosaic, identifying 81 halophyte-exclusive orthogroups and 1129 species-specific clusters. Comparative topology across six independent GRNs (4.2M-5.3 M edges) unmasked a highly modular transcriptional reprogramming strategy governed by a core apparatus of 22 stress-exclusive regulators, with functional enrichment heavily prioritizing protein dimerization and chromatin remodeling. Theoretically, the distinct convergence of Trihelix transcription factors with guard cell differentiation pathways offers a candidate transcriptomic framework to explain the plant's characteristic C4-CAM photosynthetic plasticity under severe osmotic pressure. Practically, these evolutionary blueprints and specific master switches transcend single-gene transgenic limitations. Utilizing these root-sustained and stress-inducible targets under localized promoters provides a naturally optimized, network-level precision engineering roadmap to transfer robust, compartmentalized halotolerance to sensitive glycophytic crops.

Gene Regulatory Networks↗

PubMed2025

Personalizing chemotherapy drug selection using a novel transcriptomic chemogram.

Gene signatures predictive of chemotherapeutic response have the potential to extend the reach of precision medicine by allowing oncologists to optimize treatment for individuals. Most published predictive signatures are only capable of predicting response for individual drugs, but most chemotherapy regimens utilize combinations of different agents. We propose a unified framework, called the chemogram, that uses predictive signatures to rank the relative predicted sensitivity of different drugs for individual tumors. Using this approach, providers could efficiently screen against many therapeutics to optimize chemotherapy at any time, whether it be for a treatment-naive tumor or a chemo-resistant tumor requiring a new treatment strategy. To demonstrate the utility of the chemogram, we used predictive signatures (extracted from a previously established method) in our framework to rank predicted sensitivity among drugs within cell lines. We then compared the rank order of predicted and observed response against each drug. Across most cancer types, chemogram-generated predictions were more accurate than predictions made by randomly generated gene signatures, signatures extracted from differential expression alone, and was comparable to another established method of drug response prediction. Our framework demonstrates the ability of transcriptomic signatures to not only predict chemotherapeutic response, but also correctly assign rankings of drug sensitivity on an individual basis. Additionally, scaling the chemogram to include more drugs does not compromise accuracy.

Humans↗

PubMed2025

Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.

Parkinson's disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated αSyn accelerates changes associated with normal aging. Unexpectedly, single-cell analysis at a mid-disease stage revealed that neurons upregulate protein synthesis and nonsense-mediated decay, while glia drive their overall downregulation. Longitudinal multi-omics approaches in animal models can thus help elucidate the molecular cascades underlying neurodegeneration vs. aging and co-pathologies.

Journal Article↗

PubMed2025

ANXA3 hypomethylation as a prognostic biomarker in hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a poor prognosis. This research aimed to characterize the expression pattern and clinical value of Annexin A3 (ANXA3) in HBV-ACLF patients. METHODS: First of all, ACLF-related datasets were downloaded from the Gene Expression Omnibus (GEO) database to carry out bioinformatics analyses. RT-qPCR, ELISA, and Methylight were used to measure ANXA3 gene expression and promoter methylation levels. A validation cohort was leveraged to further validate the results. RESULTS: Transcriptome analysis showed that ANXA3 was among the most differentially expressed genes when comparing dead patients with HBV-ACLF to those with survivors. The mRNA and serum levels of ANXA3 were elevated, and methylation levels were decreased in HBV-ACLF patients. The PMR value of ANXA3 in patients with HBV-ACLF was negatively correlated with inflammation-related cytokines IL-6, TNF-α, and IL-1β, as well as quantitative clinical parameters AST, TBIL, PT, INR, NEUT%, and MELD score, and positively correlated with PTA (all p < 0.05). In HBV-ACLF patients, ANXA3 was considered to be an independent influence factor for the 90-day mortality. It was also found that ANXA3, especially hypomethylation, was associated with 28- and 90-day overall survival in patients with HBV-ACLF based on receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and Kaplan-Meier curves. CONCLUSIONS: ANXA3 hypomethylation has a prominent predictive value for short-term mortality in patients with HBV-ACLF and may serve as a promising biomarker of HBV-ACLF prognosis.

Humans↗

PubMed2025

Transcriptional regulation reveals potent drought tolerance mechanisms in contrasting genotypes of Cajanus cajan (L.) Millspaugh.

Global warming severely impacts crop productivity, particularly in the Global South. Tropical pulse crops are nutritious staples and tolerant to harsh conditions, such as pigeonpea (Cajanus cajan). Two pigeonpea varieties have superior qualities, also with respect to abiotic stress tolerance: drought-tolerant Pusa Arhar 16 (PA16) and moderately drought-sensitive Pusa 992 (PA99). However, both are understudied at the molecular level. This study investigates molecular mechanisms of drought tolerance by investigating their responses to polyethylene glycol-induced drought. Superior drought tolerance in PA16 was characterized by enhanced shoot growth, photosynthetic characteristics and reduced oxidative stress as compared to PA992, while root length showed no significant difference between the varieties. Transcriptomic analysis identified differentially expressed genes among treatments and varieties, significantly upregulated under drought in PA16 versus PA992 with distinct patterns. For example, genes encoding terpenoid biosynthesis were up-regulated only in PA16, while those encoding LATE EMBRYOGENESIS ABUNDANT (LEA) proteins were drought-induced in both, PA16 and PA992. Functional enrichment analyses coupled with Weighted Correlation Network Analysis uncovered co-expression networks regulating drought-related pathways. Hence, the genotype and environment-specific gene regulation patterns suggest molecular and physiological mechanisms related to secondary metabolisms and LEA proteins underlying drought resilience in pigeonpea. This research offers potential targets for breeding drought-tolerant varieties of this important legume crop.

Cajanus↗