Frontiers in Genetics最新文献

{"title":"Calculating maternal polygenic risk scores from prenatal screening by cell-free DNA data.","authors":"Victoria Corey, Mauro Chavez, Layla Qasim, Tevfik U Dincer, Angela Henry, Salome Bagayan, Sasha Treadup, Mike Mehan, Eileen de Feo, Sung Kim","doi":"10.3389/fgene.2025.1495604","DOIUrl":"10.3389/fgene.2025.1495604","url":null,"abstract":"<p><p>Polygenic Risk Scores (PRS) have enabled quantification of genetic risk for many common and complex traits. Here we developed a novel method to estimate maternal PRS using low-coverage whole genome sequencing data from prenatal screening by cell-free DNA data intended to screen for fetal chromosomal aneuploidies. A prospective study was conducted where 455 consented patients that performed prenatal screening by cell-free DNA as part of their standard of care were randomly selected. Cell-free DNA and genomic DNA were isolated from the plasma and buffy coat of the blood drawn from pregnant women, respectively. Cell-free DNA was sequenced at ∼0.25x coverage while genomic DNA was sequenced at ∼15x coverage. The sequence data was used to impute genotypes which were then used to calculate PRS for paired comparisons. There was a high correlation (average = ∼0.9 across different PRS panels and panel sizes) between PRS from prenatal screening by cfDNA data and PRS from genome sequence data of the buffy coat. This proof-of-concept study illustrates that maternal PRS can be calculated using low-coverage prenatal screening by cfDNA sequence data with high accuracy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1495604"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572758","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":"High-throughput microRNA sequencing in the developing branchial arches suggests miR-92b-3p regulation of a cardiovascular gene network.","authors":"Sian Goldsworthy, Marta Losa, Nicoletta Bobola, Sam Griffiths-Jones","doi":"10.3389/fgene.2025.1514925","DOIUrl":"10.3389/fgene.2025.1514925","url":null,"abstract":"<p><p>Vertebrate branchial arches (BAs) are a developmental paradigm, undergoing coordinated differentiation and morphogenesis to form various adult derivative tissues. MicroRNAs can strengthen gene regulatory networks (GRNs) to promote developmental stability. To investigate microRNA-mediated regulation in BA development, we generated a novel microRNA-sequencing dataset from mouse BAs. We identified 550 expressed microRNAs, of which approximately 20% demonstrate significant differential expression across BA domains. The three most posterior BAs and the connecting outflow tract (PBA/OFT) express genes important for cardiovascular development. We predicted microRNA-target interactions with PBA/OFT-expressed cardiovascular genes and found target sites for miR-92b-3p to be enriched. We used a dual luciferase assay to validate miR-92b-3p interactions with two transcripts encoding the fundamental cardiac transcription factors (TFs), <i>Gata6</i> and <i>Tbx20</i>. Furthermore, we demonstrated that miR-92b-3p mimic can downregulate endogenous <i>GATA6</i> and <i>TBX20</i> in human embryonic stem cells (hESCs) undergoing cardiomyocyte differentiation, confirming microRNA-target binding can occur in a cardiac cell type. miR-92b-3p has previously been shown to target transcripts encoding for two other cardiac TFs, <i>Hand2</i> and <i>Mef2D.</i> Therefore, we hypothesise that miR-92b-3p acts to stabilise cardiovascular GRNs during PBA/OFT development, through multiple microRNA-mediated regulatory networks.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1514925"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572750","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":"Corrigendum: Integrated network analysis to identify key modules and potential hub genes involved in bovine respiratory disease: a systems biology approach.","authors":"Aliakbar Hasankhani, Abolfazl Bahrami, Negin Sheybani, Farhang Fatehi, Roxana Abadeh, Hamid Ghaem Maghami Farahani, Mohammad Reza Bahreini Behzadi, Ghazaleh Javanmard, Sadegh Isapour, Hosein Khadem, Herman W Barkema","doi":"10.3389/fgene.2025.1572285","DOIUrl":"https://doi.org/10.3389/fgene.2025.1572285","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgene.2021.753839.].</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1572285"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572781","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":"Correlation and clinical significance of GSTP1 hypermethylation in hepatocellular carcinoma: a systematic review and meta-analysis.","authors":"Pengfei Li, Lei He, Chunxia Zhang, Xinyao Huang, Rong Sun, Yan Zhang, Yan Wang","doi":"10.3389/fgene.2025.1543261","DOIUrl":"10.3389/fgene.2025.1543261","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the most prevalent and fatal cancers globally, with poor prognosis due to late-stage diagnosis and limited early detection methods. GSTP1 gene hypermethylation has been implicated in various cancers, including HCC, as a potential biomarker for diagnosis, prognosis, and therapeutic strategies. This systematic review and meta-analysis aimed to assess the association between GSTP1 hypermethylation and HCC, and its clinical significance.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library to identify studies examining GSTP1 hypermethylation in HCC. Studies included in the meta-analysis were observational (case-control, cohort) or experimental studies (clinical trials) that reported on the correlation between GSTP1 hypermethylation and clinical outcomes in HCC patients. Pooled odds ratios (ORs) and weighted mean differences (WMDs) were calculated using random or fixed-effects models based on heterogeneity.</p><p><strong>Results: </strong>A total of 10 case-control studies were included, comprising 1,133 participants. The analysis revealed a significant association between GSTP1 hypermethylation and the presence of HCC (OR = 6.64, 95% CI: 2.17-20.38). GSTP1 hypermethylation was more frequently observed in liver cancer tissue compared to liver tissue from patients with other diseases (P < 0.00001). Additionally, a significant correlation between GSTP1 hypermethylation and poor clinical outcomes, such as advanced tumor stage, recurrence, and reduced overall survival, was observed (OR = 2.56, 95% CI: 1.80-3.64). Subgroup analyses based on study design, sample type, and detection method showed no significant heterogeneity in most comparisons.</p><p><strong>Conclusion: </strong>GSTP1 hypermethylation is significantly associated with the presence of HCC and poorer clinical outcomes, making it a promising biomarker for early diagnosis and prognosis. These findings highlight the potential for GSTP1 methylation as a diagnostic and prognostic tool in HCC management. Further large-scale, multicenter studies are required to standardize detection methods and evaluate the therapeutic potential of epigenetic reactivation of GSTP1 in HCC patients.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1543261"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572777","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 role of CNIH4 in pan-cancer landscapes and its significance in breast cancer progression.","authors":"Yao Xu, Zengzhen Lai, Chaolin Li","doi":"10.3389/fgene.2025.1536620","DOIUrl":"10.3389/fgene.2025.1536620","url":null,"abstract":"<p><strong>Background: </strong>The escalating global cancer burden necessitates the development of biomarkers with enhanced specificity and sensitivity for early diagnosis and therapeutic efficacy monitoring. The CNIH4 gene, an emerging biomarker, is increasingly recognized for its role in the malignant progression across various cancers.</p><p><strong>Methods: </strong>We conducted a comprehensive multi-omics analysis of CNIH4, including pan-cancer expression profiles, epigenetic alterations, immune microenvironment characteristics, and therapeutic response patterns. Our focus was on clinical features, molecular underpinnings, and drug sensitivity in breast cancer (BRCA) associated with CNIH4. <i>In vitro</i> studies were also performed to assess the effects of CNIH4 knockdown on cell proliferation and cell cycle in the MDA-MB-231 cell line.</p><p><strong>Results: </strong>CNIH4 upregulation was observed in multiple cancers, significantly correlating with genomic instability. High CNIH4 expression levels were linked to poor prognosis across cancers and associated with key cancer-related pathways, particularly those in cell cycle regulation and DNA repair. Correlation analyses suggest a role for CNIH4 in the tumor immune microenvironment, as evidenced by its association with immune subtypes, immune-related genes, and immune cell infiltration. Single-cell and spatial transcriptome analyses confirmed that CNIH4 expression in BRCA predicts tumor malignancy. Drug sensitivity analysis revealed a significant correlation between CNIH4 and responsiveness to various kinase inhibitors and chemotherapeutic agents. <i>In vitro</i> experiments demonstrated that CNIH4 knockdown significantly impacts the proliferation and cell cycle of MDA-MB-231 cells.</p><p><strong>Conclusion: </strong>Our study highlights CNIH4 as a promising pan-cancer biomarker with significant implications for tumor progression and a critical role in cell cycle regulation in BRCA.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1536620"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572785","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":"EDN1 and NTF3 in keloid pathogenesis: computational and experimental evidence as novel diagnostic biomarkers for fibrosis and inflammation.","authors":"Hui Gong, Jing Liu, Nanji Chen, Hengguang Zhao, Bailin He, Hongpei Zhang, Wenping Wang, Yi Tian","doi":"10.3389/fgene.2025.1516451","DOIUrl":"10.3389/fgene.2025.1516451","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the roles of oxidative stress-related differentially expressed genes (OSRDEGs) in keloid formation and explore their potential value in diagnosis and treatment.</p><p><strong>Methods: </strong>Gene expression data from the GEO database, including GSE145725 and GSE44270 as training sets and GSE7890 as a validation set, were utilized. OSRDEGs were identified, followed by Weighted Gene Co-expression Network Analysis (WGCNA), GO/KEGG enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Key genes were further screened through protein-protein interaction (PPI) network analysis and receiver operating characteristic (ROC) curve analysis. miRNA targets, transcription factors (TF), and potential drug targets of these genes were predicted. Immune cell infiltration analysis was performed to assess the association between OSRDEGs and immune cells, which was validated using GSE7890. Finally, the expression of key genes was experimentally validated using quantitative PCR (qPCR), immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining.</p><p><strong>Results: </strong>A total of 13 OSRDEGs were identified. WGCNA and functional enrichment analyses revealed that these genes were primarily involved in fibrosis and inflammatory processes in keloids, such as the MAPK signaling pathway, lymphocyte and monocyte proliferation, and inflammatory pathways involving IL-18 and IL-23. PPI network analysis, ROC analysis, and immune infiltration results identified Endothelin-1 (EDN1) and Neurotrophin-3(NTF3) as key genes with high sensitivity and specificity. These genes were positively and negatively correlated with activated mast cells, respectively, suggesting their dual regulatory roles in fibrosis and inflammation. External dataset validation, qPCR, correlation analysis, HE staining, and IHC results demonstrated that EDN1 and NTF3 were highly expressed in keloid tissues and were associated with excessive collagen deposition and immune cell infiltration.</p><p><strong>Conclusion: </strong>EDN1 and NTF3, as OSRDEGs, play critical roles in the pathogenesis and progression of keloids. They may contribute to fibrosis and inflammation through the regulation of oxidative stress, the MAPK signaling pathway, and mast cell activation. These findings highlight EDN1 and NTF3 as potential diagnostic biomarkers and therapeutic targets, providing novel insights into the pathogenesis and treatment strategies for keloids.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1516451"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572749","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":"Editorial: Advancements and prospects of genome-wide association studies.","authors":"Ayo P Doumatey, Yafang Li, Juan Carlos Fernandez-Lopez","doi":"10.3389/fgene.2025.1564006","DOIUrl":"10.3389/fgene.2025.1564006","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1564006"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566565","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 cancer-associated fibroblast signature genes for prognostic prediction in colorectal cancer.","authors":"Wei Jin, Yuchang Lu, Jingen Lu, Zhenyi Wang, Yixin Yan, Biao Liang, Shiwei Qian, Jiachun Ni, Yiheng Yang, Shuo Huang, Changpeng Han, Haojie Yang","doi":"10.3389/fgene.2025.1476092","DOIUrl":"10.3389/fgene.2025.1476092","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblasts are an essential part of the tumor immunoenvironment, playing key roles in malignancy progression and treatment response. This study was to characterize cancer-associated fibroblasts-related genes (CAFs) in colorectal cancer (CRC) and establish signature genes associated with CAF for prognosis prediction.</p><p><strong>Methods: </strong>We downloaded single-cell RNA sequencing (scRNA-seq) data from the GEO database and bulk RNA-seq data from TCGA database to identify differentially expressed genes related to fibroblasts. In the TCGA set, DEGs were identified from tumor samples, and the WGCNA method was utilized to identify module genes. By comparing the WGCNA module genes with tumor fibroblast-related DEGs, we took the overlapped cohorts as crucial CAFs. Moreover, the prognostic CAFs were identified using univariate analysis. A CAFs risk model was established using the LASSO algorithm and then validated using external datasets. Ultimately, the expression of prognostic CAFs in CRC was confirmed using qRT-PCR.</p><p><strong>Results: </strong>A large cohort of DEGs were identified as CAFs, with eight demonstrating prognostic significance. These CAFs were primarily related to seven pathways, including peroxisome function, B cell receptor signal, and cell adhesion molecule. The CAFs risk model exhibited high accuracy for predicting prognosis, as confirmed through validation using external independent cohorts. Additionally, the risk signature showed significant correlations with immune-related scores, tumor purity, estimate, and stromal scores. qRT-PCR validated that the expression level of RAB36 was significantly downregulated in the HCT116 and HT29 cell lines compared to the NCM460 cells. Conversely, CD177, PBX4 and CCDC78 were upregulated in the HCT116 and HT29 cell lines, and ACSL6 and KCNJ14 only in HCT116 cells (<i>P</i> < 0.05). The expression trends of CD177 and CCDC78 were consistent with our predicted results.</p><p><strong>Conclusion: </strong>The CAFs risk model accurately predicted prognosis, immune cell infiltration, and stromal estimates. The prognostic CAFs (CD177 and CCDC78) may be potential therapeutic targets for CRC.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1476092"},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556650","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":"Editorial: Challenges and prospects for conservation genetics at XXI century.","authors":"Patricia Amavet, Gabriela P Fernández, Viviana Solís Neffa","doi":"10.3389/fgene.2025.1554590","DOIUrl":"10.3389/fgene.2025.1554590","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1554590"},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556639","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":"Editorial: Recent advances in causes, diagnosis, and therapeutics for congenital heart defects.","authors":"Xinxiu Xu, Cecilia W Lo, Lisa J Martin, Lu Han, Dongzhu Xu","doi":"10.3389/fgene.2025.1564492","DOIUrl":"10.3389/fgene.2025.1564492","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1564492"},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556641","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}