Gene最新文献

{"title":"The expression and function of Gpnmb in lymphatic endothelial cells.","authors":"Trinity A Kronk, Ernesto Solorzano, Gabrielle T Robinson, Joshua Castor, Hope C Ball, Fayez F Safadi","doi":"10.1016/j.gene.2024.148993","DOIUrl":"10.1016/j.gene.2024.148993","url":null,"abstract":"<p><p>The lymphatic system functions in fluid homeostasis, lipid absorption and the modulation of the immune response. The role of Gpnmb (osteoactivin), an established osteoinductive molecule with newly identified anti-inflammatory properties, has not been studied in lymphangiogenesis. Here, we demonstrate that Gpnmb increases lymphatic endothelial cell (LEC) migration and lymphangiogenesis marker gene expression in vitro by enhancing pro-autophagic gene expression, while no changes were observed in cell proliferation or viability. In addition, cellular spreading and cytoskeletal reorganization was not altered following Gpnmb treatment. We show that systemic Gpnmb overexpression in vivo leads to increases in lymphatic tubule number per area. Overall, data presented in this study suggest Gpnmb is a positive modulator of lymphangiogenesis.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"148993"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender difference in the association of OSBPL8 polymorphisms with nephrolithiasis within a Chinese cohort.","authors":"Haisong Lin, Suchun Wei, Shengzhu Huang, Zhen Tang, Zengnan Mo","doi":"10.1016/j.gene.2025.149218","DOIUrl":"10.1016/j.gene.2025.149218","url":null,"abstract":"<p><strong>Background: </strong>Kidney stone disease (KSD) is a common disorder of the urinary system and is closely related to genetic polymorphisms. However, the relationship between OSBPL8 polymorphisms and kidney stones has not been thoroughly investigated.</p><p><strong>Methods: </strong>Six OSBPL8 polymorphisms (rs17042391,rs17042409,rs4761431,rs7303892,rs4761434, and rs17042390) were analyzed in a Chinese case-control cohort containing 923 nephrolithiasis patients and 945 healthy controls.The association of these OSBPL8 gene polymorphisms with KSD susceptibility was analyzed using logistic regression, and examined by calculating the odds ratios (ORs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>The OSBPL8 polymorphisms (GG for rs17042391, rs17042409, rs4761431, rs7303892; AA for rs4761434; and G for rs17042390) were significantly associated with a decreased risk of KSD in females.The protected alleles (G allele of rs17042391, G allele of rs17042409, G allele of rs4761431, A allele of rs4761434, and G allele of rs17042390) were related to decreased BMI levels in KSD patients; female patients with these alleles also exhibited lower BMI, HDL, and LDL levels,the G allele of rs7303892 was linked to reduced serum cholesterol levels in these females.Additionally, the haplotype ACAAGA was associated with decreased KSD risk in females, but haplotype GGGGAG presented an opposing effect.</p><p><strong>Conclusion: </strong>Our research shows that the OSBPL8 gene polymorphisms reduced the risk of KSD in females, and were also associated with lipid-related metabolic traits.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"942 ","pages":"149218"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supervised learning approaches for predicting Ebola-Human Protein-Protein interactions.","authors":"Lopamudra Dey, Sanjay Chakraborty","doi":"10.1016/j.gene.2025.149228","DOIUrl":"10.1016/j.gene.2025.149228","url":null,"abstract":"<p><p>The goal of this research work is to predict protein-protein interactions (PPIs) between the Ebola virus and the host who is at risk of infection. Since there are very limited databases available on the Ebola virus; we have prepared a comprehensive database of all the PPIs between the Ebola virus and human proteins (EbolaInt). Our work focuses on the finding of some new protein-protein interactions between humans and the Ebola virus using some state- of-the-arts machine learning techniques. However, it is basically a two-class problem with a positive interacting dataset and a negative non-interacting dataset. These datasets contain various sequence-based human protein features such as structure of amino acid and conjoint triad and domain-related features. In this research, we have briefly discussed and used some well-known supervised learning approaches to predict PPIs between human proteins and Ebola virus proteins, including K-nearest neighbours (KNN), random forest (RF), support vector machine (SVM), and deep feed-forward multi-layer perceptron (DMLP) etc. We have validated our prediction results using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Our goal with this prediction is to compare all other models' accuracy, precision, recall, and f1-score for predicting these PPIs. In the result section, DMLP is giving the highest accuracy along with the prediction of 2655 potential human target proteins.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"942 ","pages":"149228"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PWWP2A/B: Prominent players in the proteomic landscape.","authors":"Saravanaraman Ponne, Raj Kumar Chinnadurai, Rajender Kumar, Aman Kumar Mohanty, Raimunda Sâmia Nogueira Brilhante, Trinh Thi Trang Nhung, Sudhakar Baluchamy","doi":"10.1016/j.gene.2025.149245","DOIUrl":"10.1016/j.gene.2025.149245","url":null,"abstract":"<p><p>The PWWP domain is a conserved motif unique to eukaryotes, playing a critical role in various cellular processes. Proteins containing the PWWP domain are typically found in chromatin, where they bind to DNA and histones in nucleosomes, facilitating chromatin-associated functions. Among these proteins, PWWP-domain containing proteins 2A and 2B (PWWP2A and PWWP2B), identified during the H2A interactome analysis, are DNA methyltransferase-related proteins, that are structurally disordered, except for their PWWP domain. While their precise functions remain to be fully elucidated, PWWP2A and PWWP2B have been implicated in essential processes such as embryonic development, mitotic regulation, adipose thermogenesis, transcriptional control, and DNA damage response. Their involvement in disease pathology is an emerging area of research, with PWWP2B downregulation linked to recurrent gastric cancer, promoting cell proliferation and migration. Literature reveals that the circular RNA, cPWWP2A sequesters miR-203, miR-223, and miR-27, to modulate TGF-β signalling by inhibiting key regulators like SMAD3 and SP3. Additionally, PWWP2A/B proteins may interact with P4HA3, a regulator of the TGF-β/SMAD signalling pathway that influences tumour invasiveness, though the precise nature of this interaction is not yet fully understood. The PWWP2-miRNA-TGF-β axis, particularly the PWWP2-P4HA3 association, provides valuable insights into therapeutic strategies, especially under adverse conditions where this pathway is differentially regulated. Overall, given their essential roles in fundamental cellular processes and their involvement in disease mechanisms, PWWP2A and PWWP2B proteins could be ideal targets for therapeutic intervention. Thus, these proteins occupy a prominent position in the human proteome and epigenetic landscape.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149245"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VAMP8 as a biomarker and potential therapeutic target for endothelial cell dysfunction in atherosclerosis.","authors":"Luqun Yang, Xin Guan, Jiangwei Cheng, Lin Ni, Huijing Yao, Yuping Gao, Kaiyi Zhu, Xiushan Shi, Bingjie Li, Yuanyuan Lin","doi":"10.1016/j.gene.2025.149231","DOIUrl":"10.1016/j.gene.2025.149231","url":null,"abstract":"<p><strong>Background: </strong>Endothelial cell dysfunction has a critical role in the pathophysiology of atherosclerosis. This study aims to uncover pivotal genes and pathways linked to endothelial cell dysfunction in atherosclerosis, as well as to ascertain the assumed causal effects and potential mechanisms.</p><p><strong>Methods: </strong>Datasets relevant to endothelial cell dysfunction in atherosclerosis were collected and divided into training and validation sets. Following differential analysis, we constructed a protein-protein interaction (PPI) network and a molecular interaction map of common-differentially expressed genes (co-DEGs) with proteins known to be involved in atherosclerotic endothelial cell dysfunction. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and Gene Set Enrichment Analysis (GSEA) were also conducted. Moreover, human umbilical vein endothelial cells (HUVECs) were cultured in circumstances characterized by elevated glucose levels to establish a cellular injury model simulating atherosclerotic conditions, and quantitative Polymerase Chain Reaction (qPCR) experiments were conducted to validate the differences of co-DEGs. Subsequently, the Summary-data-based Mendelian Randomization (SMR) method was employed. Additionally, we employed the Western Blot (WB) technique to validate the differential expression of VAMP8. Finally, we identified the differential expression of VAMP8 in the validation set and further validated its differential expression by collecting fresh blood samples from 20 patients with atherosclerosis and 20 healthy individuals.</p><p><strong>Results: </strong>14 co-DEGs (FABP5, GULP1, COL4A5, VAMP8, FABP4, PFN2, ANGPT2, TFPI2, NUPR1, SULF1, FGF13, BASP1, EPB41L3, and PBK) were identified. SMR analysis confirmed 10 potential causal effect genes: PSRC1, VAMP8, FES, HNRNPUL1, CFDP1, SAP130, MDN1, OPRL1, UTP11, and HOXC4. The qPCR and WB experiments demonstrated that VAMP8 was significantly upregulated in the injured HUVECs group (p < 0.0001). Compared to the control group, VAMP8 was markedly increased in the blood samples of patients with atherosclerosis (p < 0.0001).</p><p><strong>Conclusions: </strong>VAMP8 may potentially serve as a pathogenic gene in the process of endothelial dysfunction in atherosclerosis.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149231"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell type specific differences in transcriptome profiles of adipose derived stem cells and vaginal fibroblasts in patients with pelvic organ prolapse.","authors":"Yourka D Tchoukalova, Asha A Nair, Xianfeng Chen, Nan Zhang, Cheryl E Myers, Amr Badreldin, Amel Dudakovic, Lott G Lott, Alanna M Rebecca, Johnny Yi, Jeffrey L Cornella, Andre J van Wijnen","doi":"10.1016/j.gene.2025.149230","DOIUrl":"10.1016/j.gene.2025.149230","url":null,"abstract":"<p><p>This study examined the molecular phenotypes of adipose-derived stem cells (ASCs) and vaginal fibroblasts (VFBs) and assessed whether pelvic organ prolapse (POP) affects their biological properties. We performed RNA sequencing of paired ASCs and VFBs from six patients with POP and six controls (CTRL). The transcriptomes of POP and CTRL in either ASCs or VFBs were compared (DESeq2, false discovery rate (FDR) < 0.05) to identify differentially expressed genes (DEGs). The transcriptomes of VFBs were compared between POP and CTRL (non-adjusted p < 0.01) followed by Ingenuity Pathway Analysis on DEGs considering that pathways with FDR < 0.05 could be pathogenic. We also performed a pairwise comparison after combining the gene expression data of POP and CTRL for ASCs and VFBs to identify cell type specific DEGs and analyzed the functional associations among them (STRING platform). We found no DEGs between POP and CTRL in ASCs and VFBs. Less stringent statistical analysis of VFBs transcriptome showed 23 genes with higher and 29 genes with lower expression in POP compared to CTRL. Among the latter were five genes involved in the synaptogenesis pathway found to be significant. We were only able to validate POP related differences for very low density receptor (VLDLR). We found 508 DEGs with 4-fold difference between ASCs and VFBs (both POP and CTRL groups combined for each cell type) which formed cell type distinct functional networks including Homeobox transcription factors, extracellular matrix (ECM) related proteins, and growth factors. In summary, this study showed that the fibroblastic transcriptomes of VFBs and ASCs are different, and this cell type-specific difference is more prominent that the disease related effects of POP.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"942 ","pages":"149230"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of alternative splicing associated with sex and opioid effects in the axon guidance pathway.","authors":"Bruce R Southey, Gloria R Sunderland, Andrea N Gomez, Sreelaya Bhamidi, Sandra L Rodriguez-Zas","doi":"10.1016/j.gene.2025.149215","DOIUrl":"10.1016/j.gene.2025.149215","url":null,"abstract":"<p><p>The alternative splicing of a gene results in distinct transcript isoforms that can result in proteins that differ in function. Alternative splicing processes are prevalent in the brain, have varying incidence across brain regions, and can present sexual dimorphism. Exposure to opiates and other substances of abuse can also alter the type and incidence of the splicing process and the relative abundance of the isoforms produced. The disruption of alternative splicing patterns associated with sex differences and morphine exposure in the prefrontal cortex of a pig model was studied. The numbers of genes presenting one or more significant (FDR-adjusted p-value < 0.05) alternative splicing events were 933 and 1,368 genes when comparing females relative to males and morphine- relative to saline-treated animals, respectively. The sex-dependent opioid effect was most extreme in the contrast between morphine- versus saline-treated males with 1,934 significantly differentially spliced genes. The most frequent and significant alternative splicing type was skipped exon (∼56 % event), followed by retained intron (∼15 % events). The pathways encompassing a significant number of differentially spliced genes included axon guidance, glutamatergic synapses, circadian rhythm, and lysine degradation. Genes in these pathways included ROBO1, SEMA6C, GRIN3A, GRM2, ARNTL, CLOCK, HYKK, and DOT1L. Transcription factors ETV7 and DMAP1 presented a significant number of differentially spliced target genes. The distribution of the genes presenting differential alternative splicing in the axon guidance and circadian rhythm pathways indicates that this regulatory mechanism impacts hubs and peripheral genes. The identification of sexual dimorphism in the effect of morphine across multiple pathways confirms the necessity to explore the effects of drugs of abuse within sex. Altogether, our findings advance the understanding of the response to factors that can impact the activity of excitatory synapses by modulating transcriptional mechanisms that support the plasticity of the prefrontal cortex.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149215"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering genomic basis of unique adaptation of Ladakhi cattle to Trans-Himalayan high-altitude region of Leh-Ladakh in India.","authors":"Manish Tiwari, Monika Sodhi, Divya Chanda, Ranjit S Kataria, Saket K Niranjan, Inderpal Singh, Vijay K Bharti, M Iqbal, Stanzin Rabgais, Amarjeet, Prince Vivek, Parvesh Kumari, Manishi Mukesh","doi":"10.1016/j.gene.2025.149251","DOIUrl":"10.1016/j.gene.2025.149251","url":null,"abstract":"<p><p>In this study, whole genome sequence data of Ladakhi cattle from high altitude region of Leh-Ladakh and Sahiwal cattle from arid, semi-arid tropical region were compared. To gain a deeper understanding of the selective footprints in the genomes of Ladakhi and Sahiwal cattle, two strategies namely run of homozygosity (ROH), and fixation index (F_ST) were employed. A total of 975 and 1189 ROH regions were identified in Ladakhi and Sahiwal cattle, respectively. Several genes associated with high-altitude adaptation were enriched in many of the ROH hot spots in genome of Ladakhi cattle such as; HIF1A, VEGFA, VEGFC, EPHB1, ZEB1, CAV3, TEK, SENP2, GATA6, RAD51 and ADAMTSL4 etc.. The F_ST value of 0.32 also indicated strong genetic differentiation between Ladakhi and Sahiwal cattle. A total of 3616 genomic regions were identified to be under selection in the two cattle breeds. The F_ST selection signature analysis led to identification of several genes such as HIF1A, VEGFC, ZEB1, SOD1, EGLN3, EPAS1, ZNF, DYSF, ADAM, SENP2, MMP16, and CDK2 etc., that could be associated with high altitude adaptation in Ladakhi cattle. Additionally, several signalling pathways found in Ladakhi cattle like HIF1A, VEGF, DNA repair, and angiogenesis, which are associated with adaptation to high-altitude hypoxic environments. The phylogenetic, PCA and admixture analysis separated the individuals of Ladakhi and Sahiwal cattle according to their geographic origin. In the present study, the WGS data has helped to identify key genes and genic regions that contribute to high altitude adaptation in Ladakhi cattle.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149251"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic and phenotypic characteristics of ADGRV1 mutations in four children and functional validation in a zebrafish model.","authors":"Xiao Xiao, Hao Zheng, Miao Xiong, Xiaoqi Chen, Li Jiang, Yue Hu","doi":"10.1016/j.gene.2025.149246","DOIUrl":"10.1016/j.gene.2025.149246","url":null,"abstract":"<p><p>Mutations in ADGRV1 can cause seizures, but the mechanism remains unclear. The zebrafish model can be used to assess the functions of human ADGRV1 and its variant alleles during embryonic development. In this study, we summarized the phenotypic and genotypic characteristics of four children with ADGRV1 variation and based on this, we validated the ADGRV1 loss phenotype in an adgrv1-knockout zebrafish model. We retrospectively analyzed the clinical and genotypic characteristics of four pediatric patients diagnosed as having ADGRV1 mutations at Children's Hospital Affiliated to Chongqing Medical University from April 2019 to February 2022. Moreover, we used the adgrv1-knockout zebrafish larvae model and performed morphological, behavioral, and neuroelectrophysiological testing. We found that of the four included children, two had epilepsy, one had paroxysmal kinesigenic dyskinesia, and one had febrile seizure plus. Three children had a history of febrile seizures, whereas two had a family history of febrile seizures. Three children had well-controlled clinical epilepsy seizures or motor disorders. Finally, one child with spontaneous mutation had epigenetic abnormalities and comprehensive developmental delay, one had language developmental delay, and two (paternal or maternal) had a good prognosis. Regarding the zebrafish model, the cas9-control and adgrv1-edited groups demonstrated significant differences in the interocular areas of the zebrafish observed in the open field and the maximum swimming velocity under light stimulus. In neuroelectrophysiological testing, epilepsy-related signals were observed in 2 of 26 adgrv1-edited group fish. We believe that, mutations in the ADGRV1 may lead to epileptic seizures and movement disorders. The patients usually have a history of febrile seizures or a family history. Through research using the zebrafish model, it has been found that ADGRV1 mutations can affect the expression of eye and the neuromotor development of zebrafish larvae. This might be one of the reasons for epileptic seizures caused by ADGRV1 gene mutations.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149246"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identify and analyze ferroptosis-related molecular modules and immune signatures in epilepsy using microarray-based transcriptome profiling and single-cell sequencing.","authors":"Cong Huang, Fan Wei, Zhipeng You, Jiran Li, Yang Liu, Xingan Liu, Zhijie Fan, Yunmin He, Xiaoying Gao, Jiahang Sun","doi":"10.1016/j.gene.2025.149227","DOIUrl":"10.1016/j.gene.2025.149227","url":null,"abstract":"<p><p>Currently, the pathogenesis of epilepsy remains poorly understood. Although there is evidence indicating that iron death might play a significant role, its molecular immunological mechanisms are largely unknown. This study was designed to analyze and explore the molecular mechanisms and immunological characteristics of iron death-related genes in epilepsy. We obtained datasets of blood and brain tissues for epilepsy from the GEO database and the set of iron death-related genes from FerrDb. Through two machine learning algorithms, we identified three Hub genes, namely RELA, TFRC, and QSOX1. Unsupervised clustering revealed two distinct clusters. Immune infiltration analysis demonstrated that one cluster had significantly higher immune infiltration. We established an epilepsy diagnostic model and nomogram. The results were confirmed by RT-qPCR and Western Blot. Single-cell analysis showed that the SPP1 signalling pathway was overly activated in astrocytes and microglia. This study offers new perspectives and a theoretical foundation for the diagnosis of epilepsy.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149227"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}