Frontiers in Genetics最新文献

{"title":"Key genes of vitamin D metabolism and their roles in the risk and prognosis of cancer.","authors":"Sijie Zheng, Lizhu Zhu, Yufei Wang, Yixin Hua, Jie Ying, Jianxiang Chen","doi":"10.3389/fgene.2025.1598525","DOIUrl":"10.3389/fgene.2025.1598525","url":null,"abstract":"<p><p>Vitamin D is an essential vitamin for normal human metabolism and plays pivotal roles in various biological processes, such as maintaining calcium and phosphorus balance, regulating immune responses, and promoting cell differentiation while inhibiting proliferation. Vitamin D is obtained through sunlight exposure and diet, and is metabolized into its active form via hydroxylation in liver and kidney. Vitamin D deficiency is linked to various diseases, including skeletal disorders, diabetes, and cardiovascular diseases. Recent epidemiology and oncology research have demonstrated that serum vitamin D level, as well as genetic polymorphisms and expression dysregulation of genes related with vitamin D metabolism, have significantly influences on the incidence and prognosis of various types of cancer, including breast cancer, prostate cancer, liver cancer, gastrointestinal malignancy, and hematologic malignancies. The mechanisms linking vitamin D metabolism dysregulation to malignancy are multifactorial, such as the alteration in cell metabolism, proliferation, differentiation, and tumor microenvironment. These findings suggest potential therapeutic benefits of targeting the vitamin D signaling pathway for the diagnosis and treatment of cancer. However, there is still a lack of clinical applications regarding the knowledge of vitamin D metabolic pathway, and future research is urgently needed to illustrate the underlying mechanisms for the rationale design of clinical trials. Therefore, this review summarizes the metabolic pathways of vitamin D and its association with cancer, highlighting the importance of genetic polymorphisms and expression dysregulation of genes involved in vitamin D metabolism in cancer susceptibility and prognosis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1598525"},"PeriodicalIF":2.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591103","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":"<i>CYLD</i> as a key regulator of myocardial infarction-to-heart failure transition revealed by multi-omics integration.","authors":"Jingya Xu, Zhonghua Dong, Zhaodong Li, Xuan Wang","doi":"10.3389/fgene.2025.1592985","DOIUrl":"10.3389/fgene.2025.1592985","url":null,"abstract":"<p><strong>Introduction: </strong>Heart failure (HF) is the most common complication following myocardial infarction (MI) and frequently occurs during the postinfarction recovery phase. Despite the well-established association between HF and MI, the underlying molecular mechanisms driving their transition remain poorly understood.</p><p><strong>Methods: </strong>The aim of this study was to identify key regulatory genes involved in this transition via advanced computational tools. We conducted a comprehensive analysis of differentially expressed genes (DEGs) via Limma software, leveraging five independent datasets retrieved from the Gene Expression Omnibus (GEO) database: GSE59867, GSE62646, GSE168281, GSE267644, and GSE269269. Our multistep analytical pipeline included weighted gene coexpression network analysis (WGCNA) to map interacting genes, machine learning algorithms for robust classification, functional annotation via Kyoto Encyclopedia of Genes and Genomes (KEGG) to explore biological pathways, CIBERSORT correlation analysis linking hub genes with immune cell states, transcriptional regulation profiling of key hubs, and single-cell sequencing to assess the functional relevance of these hubs.</p><p><strong>Results: </strong>Our findings revealed that 413 DEGs were significantly different between MI and HF. WGCNA identified 98 genes associated with both conditions. Machine learning filtering further prioritized 10 hub genes: <i>GPER1</i>, <i>E2F5</i>, <i>DZIP3, CYLD</i>, <i>ADAMTS2</i>, <i>ZNF366</i>, <i>ST14, SNORD28</i>, <i>LHFPL2</i>, and <i>HIVEP2</i>. These hubs were significantly associated with immune-related processes, suggesting their potential role in the pathogenesis of HF after MI. Single-cell transcriptomic analysis demonstrated that <i>CYLD</i> exhibited the strongest correlation with the transition from MI to HF; using random forest modelling, we validated its predictive value in this context.</p><p><strong>Discussion: </strong>In conclusion, our study identified <i>CYLD</i> as a critical regulator of the transition from MI to HF. Our findings underscore the potential of hub genes as targets for novel therapeutic interventions aimed at mitigating MI-to-HF progression and improving patient outcomes.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1592985"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583738","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":"Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction.","authors":"Monica Sciacco, Sabrina Lucchiari, Letizia Bertolasi, Giacomo Pietro Comi, Stefania Corti, Dario Ronchi","doi":"10.3389/fgene.2025.1574381","DOIUrl":"10.3389/fgene.2025.1574381","url":null,"abstract":"<p><p>Glycogen storage disease II or Pompe disease (PD), is a rare autosomal recessive disorder due to biallelic pathogenic variants in <i>GAA</i>, resulting in the enzymatic deficiency of alpha-1,4-glucosidase. Two clinical forms are recognized, namely, early onset (EOPD) and late-onset (LOPD). We present the case of an asymptomatic 33-year-old man who underwent a genetic screening for autosomal recessive disorders (parental prenatal counselling) and was found to carry the homozygous pathogenic <i>GAA</i> substitution NM_000152.5(GAA):c.-32-13T>G (IVS1). Neurological examination, serum CK levels, electromyography, muscle MRI, respiratory and cardiac screening were reported normal. We investigated the effects of the variant at transcript and protein levels in available tissues from the proband and his parents. The IVS1-32-13T>G variant (dbSNP: rs386834236, Clin Var ID: 4,027) occurs in 90% of Caucasian LOPD patients and is associated with a broad range of symptom onset. About 50 subjects have been reported harboring this variant in homozygosis and most of them are asymptomatic, although a subset develops symptoms with time. Residual levels of alpha-1,4-glucosidase activity and protein content do not seem to reflect clinical severity in homozygous IVS1 LOPD patients.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1574381"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583739","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":"Shared pathogenesis in polycystic ovaries and rheumatoid arthritis: an analysis of key genes and pathways.","authors":"Yingying Ji, Pengcheng Xia, Yan Wang, Yang Liu, Feng Wang, Fenggang Sun, Qiang Feng, Qingbin Ni, Yi Li","doi":"10.3389/fgene.2025.1554139","DOIUrl":"10.3389/fgene.2025.1554139","url":null,"abstract":"<p><strong>Objective: </strong>The study aims to explore the potential shared pathogenic processes between PCOS and RA through bioinformatics analysis to identify novel therapeutic targets and biomarkers for disease management.</p><p><strong>Methods: </strong>Microarray datasets for polycystic ovary and RA were obtained from the GEO database. Differential gene expression analysis identified commonly dysregulated genes in both conditions. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed to understand the biological processes and pathways associated with the differentially expressed genes (DEGs). Protein interaction analysis, machine learning algorithms, and validation analyses were employed to identify core genes with potential diagnostic value. Immune cell infiltration analysis and evaluation of hypoxia and angiogenesis scores were conducted to assess the role of the core genes in immune-related disorders.</p><p><strong>Results: </strong>Microarray analysis identified differentially expressed genes (DEGs) commonly dysregulated in PCOS and RA. GO and KEGG enrichment analyses highlighted the involvement of cell death, inflammation, and redox pathways. Ten key genes were identified through protein interaction analysis, and machine learning further narrowed it down to six core genes: CSTA, DPH3, CAPZA2, GLRX, CD58, and IFIT1. The core genes were overexpressed in PCOS and RA tissues, suggesting their potential involvement in disease development. Validation analyses confirmed the diagnostic potential of these genes, especially in RA. Immune cell infiltration analysis correlated the expression of core genes with neutrophil and CD8⁺ T cell infiltration. Hypoxia and angiogenesis scores indicated the significance of these genes in immune-related disorders.</p><p><strong>Conclusion: </strong>The study unveils potential molecular links between PCOS and RA, highlighting the importance of immune dysregulation in their pathogenesis. The identified core genes offer novel therapeutic targets and potential biomarkers for disease management, providing insights into the complex interplay between these two seemingly unrelated conditions.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1554139"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583742","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":"Uncovering genetic contributors to developmental delay and intellectual disability: a focus on CNVs in pediatric patients.","authors":"Yilun Tao, Hongzhi Guo, Dong Han, Miao Yang, Ting Lun, Lihong Wang, Wenxia Song, Haiwei Wang, Xiaoze Li","doi":"10.3389/fgene.2025.1539902","DOIUrl":"10.3389/fgene.2025.1539902","url":null,"abstract":"<p><strong>Background: </strong>Developmental delay (DD) and intellectual disability (ID) are prevalent in children and often have genetic causes, particularly copy number variations (CNVs). Chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) are key diagnostic tools for identifying genetic contributions to these disorders. This study assesses the prevalence and clinical impact of CNVs in pediatric DD and ID patients.</p><p><strong>Methods: </strong>Ninety-nine pediatric patients with DD or ID underwent CMA or WES. Of these, 82 received SNP array analysis, while 17 had WES. CNV pathogenicity was assessed using established databases and ACMG guidelines, with inheritance patterns determined where possible.</p><p><strong>Results: </strong>Across the 99 patients, 43 CNVs were identified in 40 individuals, with 32 classified as clinically significant, resulting in a diagnostic rate of 30.3%. These findings included 24 deletions (75%), 7 duplications (22%), and 1 instance of loss of heterozygosity (3%). Of the CNVs with known inheritance, 65.2% were <i>de novo</i>. Recurrent CNVs made up 36.4% of the total, especially in regions 15q11.2-q13.1, 16p11.2, and 22q11.2. Additionally, 11 CNVs were categorized as variants of uncertain significance (VOUS).</p><p><strong>Conclusion: </strong>This study supports CMA as an effective diagnostic tool for DD and ID, highlighting the importance of family-based CNV testing for genetic counseling. The findings emphasize the need for comprehensive genetic testing to improve diagnostic accuracy, with future multi-omics approaches potentially clarifying VOUS mechanisms and CNV variability in neurodevelopmental disorders.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1539902"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583743","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":"Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains.","authors":"Xudong Wu, Tingting Liu","doi":"10.3389/fgene.2025.1544802","DOIUrl":"10.3389/fgene.2025.1544802","url":null,"abstract":"<p><strong>Introduction: </strong>The DNA replication of eukaryotes proceeds in a defined temporal sequence known as the replication timing (RT) program. A recent study revealed that the early- and late-replication temporal domains have different DNA mutation patterns and that the late-replicating sequences have a substitution pattern biased towards A and T. It raises the interesting question of how the miRNAs in the late-replication domain cope with the mutation bias caused by RT.</p><p><strong>Methods: </strong>In this study, we characterized the genomic distribution of pre-miRNAs in relation to DNA replication timing, and identified 362 pre-miRNAs within late-replicating domains (late-miRNAs) and 631 pre-miRNAs within early-replicating domains (early-miRNAs). We comprehensively examined the multiple molecular features including the secondary structural properties, the genomic sequences surrounding the pre-miRNA loci, the Dicer processing motifs, and CAGE tag-based promoters and miRNAs expression profiles. Furthermore, we performed the simulation of miRNA-target regulatory networks to elucidate the co-regulation patterns among late-miRNAs. To advance predictive capabilities, we developed a a support vector machine (SVM) classifier based on RNA-FM embedding, enabling prediction of miRNAs' replication timing domains.</p><p><strong>Results and discussion: </strong>Our study indicated that the late pre-miRNAs maintained their ability to fold into hairpin structures through extending their lengths at both ends under the premise of maintaining a certain GC content of the precursors. The simulation demonstrated that the late-miRNAs tend to synergistically regulate the same genes and are involved in small molecule metabolism, immune responses and so on. The comparative analysis of early- and late- miRNAs confirmed that the information of replication timing domains is inherently encoded in miRNAs' sequence-structure signatures, and suggested that late-replication specific mutation patterns leave direct imprints on miRNA architecture. This study provides insights into the impact of DNA replication timing on miRNA-mediated posttranscriptional regulation and helps us understand the evolutionary mechanism of miRNAs.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1544802"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583741","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":"Directional genomic hybridization (dGH™) identifies small inverted duplications <i>in situ</i>.","authors":"Thomas Liehr, Erin Cross, Stefanie Kankel","doi":"10.3389/fgene.2025.1604822","DOIUrl":"10.3389/fgene.2025.1604822","url":null,"abstract":"<p><p>Although fluorescence <i>in situ</i> hybridization (FISH) is a standard approach for characterizing the chromosomal structure involving a region of interest, FISH targeting single chromatids is not routinely performed. However, this latter approach seems principally well-suited to distinguish small, tandem inverted duplications from direct duplications in clinical cases. A commercially available single-chromatid FISH approach, called \"directional genomic hybridization\" (dGH™), was applied in this study to nine cases of small supernumerary marker chromosomes (sSMCs) known to contain inverted duplications. Successful detection of small inverted duplications has been demonstrated for the first time in this study using a custom KromaTiD dGH™ InSite Assay. In all five euchromatic sSMC cases, inversions were detected using the dGH single-chromatid molecular cytogenetic assay. Thus, the dGH method of FISH is a readily applicable, straightforward approach for identifying small inverted duplications that are undetectable by conventional (molecular) cytogenetic methods. This technique may be used to identify the presence of small inversions within regions presenting a copy number gain as detected by chromosome microarray. Distinguishing small inverted duplications from direct duplications may have an impact on topologically associating domains (TADs) and, thus, on clinical outcome.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1604822"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583740","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":"Integrative bioinformatics analysis of pyroptosis-related genes and immune infiltration patterns in childhood asthma.","authors":"Di Lian, Chenye Lin, Meiling Xie, JianXing Wei, Xueling Huang, Ke Lian, Qiuyu Tang","doi":"10.3389/fgene.2025.1557709","DOIUrl":"10.3389/fgene.2025.1557709","url":null,"abstract":"<p><strong>Introduction: </strong>Childhood asthma (CA) is a common chronic respiratory condition that significantly impacts the respiratory function and quality of life of affected children. With a rising global incidence, CA poses substantial physical, psychological, and economic burdens. This study aimed to elucidate the role of pyroptosis-related differentially expressed genes (PRDEGs) in CA by conducting a comprehensive bioinformatics analysis using an integrated dataset from the Gene Expression Omnibus.</p><p><strong>Methods: </strong>Differential expression analysis was performed using the R package limma, identifying 2,069 differentially expressed genes (DEGs), with 1,158 upregulated and 911 downregulated genes in CA compared with the control group. Among these DEGs, 45 PRDEGs were identified, suggesting the potential involvement of pyroptosis in the pathological processes of CA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that PRDEGs were primarily enriched in biological processes related to the immune response, cell disassembly, and inflammatory pathways.</p><p><strong>Results: </strong>Immune cell infiltration analysis using the CIBERSORT algorithm revealed significant differences between the CA and control groups, with increased macrophages M0, activated mast cells, and γδ T cells and decreased resting natural killer cells in the CA group. Among the six hub genes identified, BAX, BECN1, MAVS, and BCL2 exhibited statistically significant expression differences between the groups (p < 0.05 in GEO data; p < 0.0001 or p < 0.001 in quantitative real-time polymerase chain reaction validation), while NOD2 and NFKBIA showed no significant differences. Receiver operating characteristic analysis of BAX, BECN1, MAVS, and BCL2 supported their potential as diagnostic biomarkers for CA, with area under the curve values ranging from 0.602 to 0.621 (95% confidence interval: 0.510-0.712).</p><p><strong>Discussion: </strong>Our findings provide novel insights into the molecular mechanisms underlying CA and highlight the diagnostic potential of BAX, BECN1, MAVS, and BCL2 as biomarkers. Targeting PRDEGs may offer new therapeutic avenues, and further research is warranted to validate these findings and explore the clinical applicability of suggested biomarkers in precision medicine for managing CA.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1557709"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575343","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 neutrophil extracellular trap-related biomarkers in ulcerative colitis based on bioinformatics and machine learning.","authors":"Jiao Li, Yupei Liu, Zhiyi Sun, Suqi Zeng, Caisong Zheng","doi":"10.3389/fgene.2025.1589999","DOIUrl":"10.3389/fgene.2025.1589999","url":null,"abstract":"<p><strong>Background: </strong>The incidence of ulcerative colitis (UC) is rapidly increasing worldwide, but existing therapeutics are limited. Neutrophil extracellular traps (NETs), which have been associated with the development of various autoimmune diseases, may serve as a novel therapeutic target for UC treatment.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed to investigate UC-related datasets downloaded from the GEO database, including GSE87466, GSE75214, and GSE206285. Differentially expressed genes (DEGs) related to NETs in UC patients and healthy controls were identified using Limma R package and WGCNA, followed by functional enrichment analysis. To identify potential diagnostic biomarkers, we applied the Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE) model, and Random Forest (RF) algorithm, and constructed Receiver Operating Characteristic (ROC) curves to evaluate accuracy. Additionally, immune infiltration analysis was conducted to identify immune cells potentially involved in the regulation of NETs. Finally, the expression of core genes in patients was validated using Quantitative real-time PCR (qRT-PCR), and potential therapeutic drugs for UC were explored through drug target databases.</p><p><strong>Result: </strong>Differential analysis of transcriptomic sequencing data from UC samples identified 29 DEGs related to NETs. Enrichment analysis showed that these genes primarily mediate UC-related damage through biological functions such as leukocyte activation, migration, immune receptor activity, and the IL-17 signaling pathway. Three machine learning algorithms successfully identified core NETs-related genes in UC (IL1B, MMP9 and DYSF). According to ROC analysis, all three demonstrated excellent diagnostic efficacy. Additionally, Immune infiltration analysis revealed that the expression of these core genes was closely associated with neutrophils infiltration and CD4⁺ memory T cell activation, and negatively associated with M2 macrophage infiltration. qRT-PCR showed that the core genes were significantly overexpressed in UC patients. Gevokizumab, canakinumab and carboxylated glucosamine were predicted as potential therapeutic drugs for UC.</p><p><strong>Conclusion: </strong>By combining three machine learning algorithms and bioinformatics, this research identified three hub genes that could serve as novel targets for the diagnosis and therapy of UC, which may provide valuable insights into the mechanism of NETs in UC and potential related therapies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1589999"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575329","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":"Diagnostic yield of 1000 trio analyses with exome and genome sequencing in a clinical setting.","authors":"Helena Malmgren, Malin Kvarnung, Peter Gustafsson, Britt-Marie Anderlid, Cecilia Arthur, Jonas Carlsten, Karl De Geer, Emma Ehn, Giedre Grigelioniené, Anna Hammarsjö, Hafdis T Helgadottir, Maritta Hellström-Pigg, Erik Iwarsson, Ekaterina Kuchinskaya, Hillevi Lindelöf, Maria Mannila, Daniel Nilsson, Maria Pettersson, Eva Rudd, Ellika Sahlin, Bianca Tesi, Emma Tham, Håkan Thonberg, Eini Westenius, Johanna Winberg, Max Winerdal, Magnus Nordenskjöld, Maria Johansson-Soller, Valtteri Wirta, Ann Nordgren, Anna Lindstrand, Kristina Lagerstedt-Robinson","doi":"10.3389/fgene.2025.1580879","DOIUrl":"10.3389/fgene.2025.1580879","url":null,"abstract":"<p><strong>Introduction: </strong>A trio analysis refers to the strategy of exome or genome sequencing of DNA from a patient, as well as parents, in order to identify the genetic cause of a disorder or syndrome.</p><p><strong>Methods: </strong>During the last 10 years, we have successfully applied exome or genome sequencing and performed trio analysis for 1,000 patients.</p><p><strong>Results: </strong>Overall, 39% of the patients were diagnosed, with the detection of causative variant(s). The variants were located in 308 different genes. Autosomal dominant <i>de novo</i> variants were detected in 46% of the solved cases. Detection rates were highest in patients with a syndromic neurodevelopmental disorder (46%) and in patients with known consanguinity (59%). Even for patients previously analyzed as singletons, using a pre-defined gene panel, a consecutive trio analysis resulted in the detection of a causative variant in 30%.</p><p><strong>Discussion: </strong>A major advantage of trio analysis is the immediate identification of <i>de novo</i> variants as well as confirmation of compound heterozygosity. Additionally, inherited variants from a healthy parent can be dismissed as non-disease causing. The trio strategy enables analysis of a high number of genes-or even the whole genome-simultaneously. The strengths of a trio analysis, in combination with analysis of genome sequence data, allows for the detection of a wide range of genetic aberrations. This enables a high diagnostic yield, even in previously analyzed patients. Our current protocol for trio analysis is based on genome sequencing data, which allows for simultaneous detection of single nucleotide variants, insertion/deletions, structural variants, expanded short tandem repeats, as well as a copy number analysis corresponding to an array-CGH, and analysis regarding <i>SMN1</i> gene copies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1580879"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575327","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}