Frontiers in Genetics最新文献

{"title":"Identification of platelet function-related genes in STEMI patients.","authors":"Jingjing Zhu, Shuangya Yang, Qing Guo, Yifan Yang, Bei Shi","doi":"10.3389/fgene.2025.1651794","DOIUrl":"10.3389/fgene.2025.1651794","url":null,"abstract":"<p><strong>Background: </strong>ST-elevation myocardial infarction (STEMI) is characterized by extensive myocardial necrosis due to acute and severe ischemia, with platelets playing a key role in its pathogenesis. This study aimed to identify platelet function-related biomarkers in STEMI patients.</p><p><strong>Methods: </strong>The GSE59867 dataset, including STEMI patients and controls, was analyzed to identify differentially expressed genes (DEGs) using the limma R package. Platelet function-related DEGs (DEPRGs) were obtained by intersecting DEGs with platelet-related genes. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed using STRING, followed by identification of hub genes via Cytohubba. The diagnostic value of these genes was evaluated through receiver operating characteristic (ROC) analysis, and further expression validation along with ROC validation was conducted in the GSE123342 dataset. Additionally, gene expression was validated by quantitative real-time polymerase chain reaction (RT-qPCR) in peripheral blood from STEMI patients and cardiac tissue from STEMI mouse models.</p><p><strong>Results: </strong>A total of 245 DEPRGs were identified; enrichment analyses revealed their primary involvement in hemostasis, coagulation, and platelet activation (adjusted <i>P</i> < 0.05). The PPI network screening identified 11 hub genes, among which GRB2, MAPK1 (ERK2), MAPK3 (ERK1), PIK3CA, AKT1, and PIK3R1 demonstrated strong diagnostic performance (AUC > 0.7). ROC analysis yielded the following AUC values (95% CI): GRB2 0.759 (0.678-0.835), MAPK1 0.736 (0.650-0.810), MAPK3 0.824 (0.752-0.885), PIK3CA 0.806 (0.735-0.868), AKT1 0.724 (0.633-0.807), and PIK3R1 0.809 (0.732-0.879); all P-values were <0.05 after adjustment for multiple comparisons. Further validation in an independent dataset confirmed that MAPK3 (<i>P</i> = 1.6 × 10^-5) and GRB2 (<i>P</i> = 8.2 × 10^-7) exhibited consistent expression trends with the training set, with ROC analysis showing AUC values greater than 0.7 for both genes (MAPK3: AUC = 0.808 [95% CI: 0.709-0.899]; GRB2: 0.759 AUC = [95% CI: 0.765-0.929]). Thus, MAPK3 and GRB2 were identified as key genes. qPCR validation in peripheral blood from STEMI patients (n = 30) and cardiac tissue from a mouse myocardial infarction model further confirmed the differential expression of GRB2 and MAPK3 (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>This study identified two platelet function-related genes, MAPK3 and GRB2, as potential biomarkers for STEMI, demonstrating high clinical relevance and diagnostic value.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1651794"},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slavs in the closet: computational genomic analysis reveals cryptic slavic signatures in the Avar Khaganate and their contribution to medieval Croatian population formation.","authors":"Todor Chobanov, Svetoslav Stamov","doi":"10.3389/fgene.2025.1610942","DOIUrl":"10.3389/fgene.2025.1610942","url":null,"abstract":"<p><p>Our study applies a systematic computational genomic approach to investigate the complex population dynamics of Southern Slavs in the Hungarian Plain and Avar Khaganate, and their subsequent role in forming the medieval Croatian population. Using a quality-controlled dataset of 1,800 ancient DNA samples, we implemented a comprehensive analytical framework centered on systematic screening of marginal Principal Components to detect cryptic Slavic genetic signatures. This strategic methodological approach addresses the well-documented analytical challenge that Germanic and Slavic populations remain indistinguishable using conventional PC1-2 analysis due to shared Baltic Bronze Age ancestry. Through systematic evaluation of all principal components (PC1-20), we identified PC9 as a reliable indicator of Slavic ancestry within European ancient DNA samples when combined with PC4 and PC3. This approach revealed substantial Baltic genetic components in early Slavic populations (57% in Slovakia/Slovenia) decreasing to 39%-51% in medieval Croatian samples. Statistical modeling demonstrates that contemporary Croatian populations formed through three distinct migration waves, with 50%-60% total Slavic ancestry and 20%-25% pre-Slavic Balkan continuity. Significantly, we identified individuals with Slavic genetic profiles in prestigious Avar burial contexts, questioning established understanding of social hierarchies within the Khaganate. The genomic evidence indicates that key aspects of South Slavic genetic structure emerged through interactions within the Carpathian Basin rather than after Balkan arrival. Our findings demonstrate that Croatian ethnogenesis involved gradual integration rather than population replacement, with the Avar Khaganate serving as a crucial demographic interface where South Slavic genetic structure emerged. Our approach addresses longstanding historical questions regarding Croatian ethnogenesis by identifying specific genetic signatures and quantifying their population-level contributions, demonstrating how application of computational genomics provides unprecedented resolution in studying complex population transformations when traditional historical and archaeological approaches reach interpretive limits.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1610942"},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel <i>COL2A1</i> mutation in a Chinese family with predominantly ocular Stickler syndrome.","authors":"Yanyu Lin, Xin Liu, Shuxian Lin, Jiansheng Lin","doi":"10.3389/fgene.2025.1646923","DOIUrl":"10.3389/fgene.2025.1646923","url":null,"abstract":"<p><strong>Purpose: </strong>The ocular-only variant of Stickler syndrome type I (OSTL1) is an autosomal dominant connective tissue disorder characterized by ocular abnormalities with minimal or absence of systemic involvement. This study aimed to investigate the clinical features and molecular etiology of predominantly ocular Stickler syndrome in a multigenerational pedigree.</p><p><strong>Methods: </strong>Comprehensive ophthalmic, audiological, and physical examinations were conducted on family members with predominantly ocular Stickler syndrome. Whole exome sequencing (WES) was conducted on the proband, and Sanger sequencing was used to confirm co-segregation of the identified mutation within the family.</p><p><strong>Results: </strong>Two affected individuals were identified, both presenting with myopia, megalophthalmos, retinal tears and detachment, vitreous opacification, chorioretinal scars, and early-onset cataracts. The proband's mother had complete vision loss in her right eye. In terms of extraocular findings, the proband presented with scoliosis, and the proband's mother had mild hearing loss in both ears. A novel likely pathogenic (LP) frameshift mutation c.3534dupT (p.Gly1179Trpfs*74) in exon 50 of the <i>COL2A1</i> was identified in both affected individuals and absent in unaffected family members. This mutation was not found in the ESP, 1000 Genomes, or EXAC databases and is predicted to cause protein truncation.</p><p><strong>Conclusion: </strong>This study reports, for the first time, the clinical manifestations associated with a novel <i>COL2A1</i> exon 50 mutation in a family with predominantly ocular Stickler syndrome. Our findings expand the known mutational spectrum of <i>COL2A1</i> and further illustrate the phenotypic variability of an ocular variant of Stickler syndrome type I with minimal systemic manifestations. These results highlight the importance of early screening in individuals at risk to enable timely diagnosis and management.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1646923"},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond single references: pangenome graphs and the future of genomic medicine.","authors":"Denis M Nyaga, Roan E Zaied, Olin K Silander, Michael A Black, Justin M O'Sullivan","doi":"10.3389/fgene.2025.1679660","DOIUrl":"10.3389/fgene.2025.1679660","url":null,"abstract":"<p><p>Genomic medicine relies on single reference genomes that miss crucial genetic diversity, creating diagnostic gaps that disproportionately affect underrepresented populations. Pangenome graphs, collections of diverse genomes represented as interconnected genetic paths, offer a powerful alternative to the standard reference genome approach. Pangenome-based approaches capture the spectrum of human variation, dramatically improving how we detect complex structural variants, reconstruct haplotypes, and reduce bias in genetic studies. Projects like the Human Pangenome Reference Consortium have identified hundreds of megabases of missing genetic diversity, leading to remarkable improvements in variant detection across different populations. Yet, as pangenomes grow larger and computationally complex, they become more challenging to interpret clinically, creating a trade-off between comprehensiveness and usability. This review discusses the technical and conceptual advances enabling clinical applications of pangenomes in rare disease diagnosis. Realizing the future potential of pangenome graphs in genomic medicine will require innovative implementation strategies, thorough clinical testing, and user-friendly approaches.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1679660"},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential impact of GLS and PDHA1 on tumor immunity and immunotherapy response in LUSC.","authors":"Tianhe Ling, Jiahui Wu, Ling Xiaohao","doi":"10.3389/fgene.2025.1606111","DOIUrl":"10.3389/fgene.2025.1606111","url":null,"abstract":"<p><strong>Background: </strong>Lung squamous cell carcinoma (LUSC), a therapeutically challenging non-small cell lung cancer (NSCLC) subtype with a poor prognosis, exhibits heterogeneous responses to immunotherapy. Cuproptosis, a recently discovered regulated cell death pathway, has been hypothesised to modulate the tumour immune microenvironment (TIME). Despite the well-established role of PDHA1 as a metabolic regulator, the specific mechanisms by which it interacts with GLS in cuproptosis-mediated immune-metabolic crosstalk remain to be elucidated in LUSC. The present study investigates the manner in which GLS/PDHA1 expression patterns influence TIME composition and contribute to the stratification of immunotherapy responsiveness.</p><p><strong>Methods: </strong>It was determined that GLS and PDHA1 were the most significant copper oxidation-related genes, due to their highest absolute correlation with the ESTIMATE immune score. A consensus clustering analysis was conducted on a cohort of 501 TCGA-LUSC patients, with the objective of stratifying patients based on GLS/PDHA1 expression levels. Quantitative analysis of immune infiltration was performed using ESTIMATE, CIBERSORT, and ssGSEA methods. The pathway enrichment analysis was conducted using GSEA and WGCNA. A detailed analysis of 17,050 single-cell RNA sequencing (scRNA-seq) data from two LUSC patients was conducted, which revealed unique gene expression patterns. The validity of these findings was confirmed through the integration of four independent GEO cohorts (GSE181043/37745/43580/115457; n = 278).</p><p><strong>Results: </strong>Consensus clustering delineated two subtypes:Cluster 1 (low GLS/high PDHA1) and Cluster 2 (high GLS/low PDHA1). Cluster two showed enhanced immune infiltration, characterized by: Elevated immune checkpoint expression and Enriched T-cell activation pathways. Validation across four GEO cohorts confirmed Cluster two conserved immune-hot phenotypewith elevated ESTIMATE stromal scores, reduced tumor purity, and activated immune subsets. scRNA-seq identified malignant epithelial cells as the hub of divergent GLS/PDHA1 expression (high GLS/low PDHA1), orchestrating cuproptosis-immunometabolic crosstalk.</p><p><strong>Conclusion: </strong>GLS and PDHA1 have been proposed as potential prognostic markers for immunotherapy. Targeting cuproptosis has the potential to convert immunologically cold to hot tumours, thereby advancing precision immunotherapy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1606111"},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the shared genetic structure between hip osteoarthritis and femoral neck bone mineral density.","authors":"Jianguo Zhou, Junfu Na, Zongkun Jiang, Xiaoyan Dou, Shixuan Wang, Hongtao Li, Jian Kang","doi":"10.3389/fgene.2025.1597005","DOIUrl":"10.3389/fgene.2025.1597005","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;While the association between hip osteoarthritis (HOA) and femoral neck bone mineral density (FN-BMD) is established, their shared genetic architecture remains elusive. This study aims to explore the genetic correlation and underlying mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The present study applied bidirectional Mendelian randomisation (MR) to investigate causal relationships between HOA and FN-BMD. The quantification of genetic correlations was achieved by employing linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) inference. Multi-trait analysis of genome-wide association studies (MTAG) have been shown to enhance statistical resolution, thereby unveiling hitherto unreported genetic associations. Independent MTAG-HOA risk loci were identified through conditional joint analysis (GCTA-COJO), complemented by functional mapping and annotation (FUMA) functional annotation. The application of both MAGMA and GCTA-fastBAT has revealed pleiotropic genes linked to MTAG-HOA susceptibility. Integration of fine-mapped genes from these loci with risk-associated candidates has enabled the identification of 13 key HOA-related genes. Functional annotation of these 13 key genes was performed using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses. Multi-tissue transcriptome-wide association studies (TWAS) explored the expression of key genes across different tissues and their association with HOA. SMR analysis evaluated the causal relationship between key gene expressions in various tissues and HOA. Proteomic profiling is conducted via proteome-wide association studies (PWAS) and biomarker level imputation from summary statistics (BLISS). The application of stratified LDSC-SEG has revealed a genetic enrichment profile in cell types.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Bidirectional MR analysis revealed a significant negative causal effect of FN-BMD on HOA (β = -2.17, P &lt; 0.01), whereas the reverse MR analysis did not identify a causal effect. LDSC and HDL analyses revealed genetic correlations between HOA and FN-BMD of rg = 0.132 and rg = 0.1697, respectively. GCTA-COJO and FUMA collectively identified 28 independent risk SNPs associated with HOA. MAGMA and GCTA-fastBAT identified 48 pleiotropic genes. Integrating independent risk loci and pleiotropic genes culminated in the identification of 13 key genes associated with HOA. An enrichment analysis revealed that 13 key genes were significantly associated with biological processes integral to cartilage development, osteogenesis, cell proliferation, apoptosis, and stem cell differentiation. Multi-tissue TWAS and SMR analyses indicated that seven genes were associated with HOA across 22 tissues, with brain tissues accounting for 28.6%. Furthermore, PWAS and BLISS methods were utilized to analyze the proteomic features of these key genes. LDSC-SEG analysis revealed enrichment of HOA heritability in Carti","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1597005"},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hypergraph neural network for prioritizing Alzheimer's disease risk genes.","authors":"Meng Ma, Chao Deng, Yan Liu, Qingqing Cao, Fang Liu, Yan Zhang","doi":"10.3389/fgene.2025.1668200","DOIUrl":"10.3389/fgene.2025.1668200","url":null,"abstract":"<p><p>Identifying the complex genetic architecture of Alzheimer's disease (AD) is critical for understanding its pathophysiology. While network-based computational methods assist in this task, they primarily model simple pairwise gene interactions and fail to capture the higher-order associations of genes that drive complex diseases. To address this limitation, we introduce HyperAD, a novel hypergraph neural network framework designed to predict AD risk genes by explicitly modeling these higher-order associations of genes. HyperAD constructs a hypergraph in which functional gene sets from databases such as MSigDB form hyperedges, and uses a two-stage hypergraph message passing neural network to extract high-order association information from the hypergraph. Comprehensive evaluations demonstrate that HyperAD significantly outperforms state-of-the-art methods. We validate the prediction results of HyperAD through multiple lines of evidence. HyperAD-predicted genes are enriched in AD-related biological processes and have significant associations with known related genes in terms of sequence similarity, protein interaction, and miRNA. In addition, their protein expression levels are significantly altered in the brains of AD patients, and they contain both known risk sites and new, high-confidence candidate genes. HyperAD provides a more accurate and biologically insightful tool for prioritizing genes and unraveling the complex genetic landscape of AD.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1668200"},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of prognostic and cellular senescence gene E2F1 of papillary thyroid carcinoma through bioinformatics analyses and experimental verification.","authors":"Bin Yu, Shu-Yan Zhao, Yun-Hua Zhu, Jun-Jie Luo, Ke Zheng, Bin-Jie Shen, Yi-Lin Shen, Huan-Xin Zhong","doi":"10.3389/fgene.2025.1605385","DOIUrl":"10.3389/fgene.2025.1605385","url":null,"abstract":"<p><strong>Objective: </strong>This work aimed to find a new prognostic cell senescence gene to predict the prognosis of patients with papillary thyroid carcinoma (PTC).</p><p><strong>Methods: </strong>The data of the patients with PTC were collected from the Cancer Genome Atlas (TCGA) database. The gene set of cellular senescence was collected from the website of CellAge. The function of hub genes was analyzed by various bioinformatics methods including expression analysis, survival analysis, and nomogram analyses. Real-time quantitative PCR, cell transfection, colony formation assay, Western blot, wound healing assay, transwell assay, cell counting Kit-8, flow cytometry, and immunohistochemistry staining were performed to verify the function of hub gene.</p><p><strong>Results: </strong>E2F1 was finally screened as the key senescence gene, and its expression was higher in PTC tumors than in normal. KM curve indicated that PTC patients with higher expression of the E2F1 had longer survival times. The GSEA showed that the high expression group of E2F1 was enriched in DNA replication and so on. Cell experiments showed that overexpression of E2F1 significantly increased relative protein expression of senescence related markers, including p21, p53, γ-H2AX, and p16INK4a. Cell experiments also showed that overexpression of E2F1 inhibited the invasion, proliferation, and migration of tumor cells. While knockdown of E2F1 reversed these results.</p><p><strong>Conclusion: </strong>E2F1 was found to be upregulated in PTC, with its high expression significantly correlated to a favorable patient prognosis. E2F1 suppresses malignant tumor phenotypes by modulating cellular senescence. A predictive model integrating E2F1 and clinical features accurately forecasts poor prognosis, indicating E2F1's potential as a therapeutic target for PTC.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1605385"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association analysis of resistance to bacterial cold-water disease in an important rainbow trout aquaculture breeding population.","authors":"Bruna Santana, Yniv Palti, Guangtu Gao, Vibha Tripathi, Kyle E Martin, Breno O Fragomeni","doi":"10.3389/fgene.2025.1582138","DOIUrl":"10.3389/fgene.2025.1582138","url":null,"abstract":"<p><p>Bacterial cold-water disease (BCWD) outbreaks in salmonid aquaculture have resulted in significant losses in commercial populations. Currently, there is no commercially available vaccine for the disease caused by <i>Flavobacterium psychrophilum</i>. BCWD resistance in rainbow trout exhibits moderate heritability and has been the focus of selection efforts. The understanding of key genomic regions associated with BCWD resistance has advanced since the integration of genomic information into genetic evaluations, proving successful in enhancing BCWD resistance in some commercial lines. Here, we report the results of a genome-wide association study for BCWD resistance in an important commercial rainbow trout line to further our understanding of the genetic architecture of the trait and infer a selective breeding strategy for this line. Different scenarios were tested, including the use of all single-nucleotide polymorphisms (SNPs) passing quality control, removal of SNPs with major effect, elimination of consistent \"major SNPs\" in subgroups of the population, and exclusion of SNPs within haplotypes with major effect. Prediction accuracy was evaluated with different SNP weighting strategies, utilizing cross-validation groups formed either randomly or based on principal components and cluster analyses of genotypic data. Comparative analysis of cross-validation methods suggested that partitioning of the dataset using K-means clustering reduced overfitting. The incorporation of SNP weighting further confirmed the oligogenic nature of the trait under investigation. Prediction accuracy with pedigree-based best linear unbiased prediction (PBLUP) was 0.27 and increased to 0.36 with genomic information. The accuracy obtained with a single largest effect haplotype was 0.23. Moreover, a decrease in accuracy was observed upon excluding major SNPs and haplotypes, providing supplementary evidence of their importance on phenotypes. The two largest association peaks on OmyA31/Omy25 and Omy8 were consistent with previous reports.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1582138"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics-based identification of differentially expressed genes in endometrial carcinoma: implications for early diagnosis and prognostic stratification.","authors":"Liang Gao, Donglan Yuan, Aihua Huang, Hua Qian","doi":"10.3389/fgene.2025.1631060","DOIUrl":"10.3389/fgene.2025.1631060","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to identify differentially expressed genes (DEGs) in endometrial carcinoma (EC) through bioinformatics analysis and investigate their roles in early diagnosis and prognosis.</p><p><strong>Methods: </strong>EC-related gene datasets were retrieved from the NCBI and analyzed using R packages to screen for DEGs. Primers were designed for selected DEGs, and their expression levels were validated via qPCR. Logistic regression, survival analysis, Cox proportional hazards models, and random forest models were employed to evaluate associations between DEGs and clinical outcomes.</p><p><strong>Results: </strong>Bioinformatics analysis identified significantly upregulated genes (<i>Erb-B2</i>, <i>PIK3CA</i>, <i>CCND1</i>, <i>VEGF</i>, <i>KIT</i>) and downregulated genes (<i>PTEN</i>, <i>E-cadherin</i>, <i>p53</i>). Logistic regression revealed <i>Erb-B2</i> as a protective factor against poor prognosis, whereas <i>E-cadherin</i> and <i>P53</i> were risk genes. Clinical markers CA125, CA199, and IL-9 also emerged as prognostic risk factors. Survival analysis demonstrated significant divergence between good and poor prognosis groups (<i>P</i> < 0.05), with HR < 1 for <i>Erb-B2</i> and <i>p53</i> (protective effects) and HR > 1 for <i>E-cadherin</i>, CA125, CA199, and IL-9 (risk effects). The random forest model highlighted CA199 as a pivotal prognostic biomarker, while decision tree analysis enabled effective patient stratification based on CA125 and CA199 thresholds.</p><p><strong>Conclusion: </strong>The identified DEGs and clinical indicators hold significant potential for improving early diagnosis and prognostic evaluation in EC. These findings provide novel biomarkers and theoretical foundations for precision medicine, guiding risk stratification and personalized therapeutic strategies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1631060"},"PeriodicalIF":2.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}