Pub Date : 2025-11-01Epub Date: 2025-09-30DOI: 10.1016/j.ygeno.2025.111126
Hongwei Jin , Bin Feng , Wenxiao Gong, Xiaoliang Chen, Dongli Wang, Yan Li, Weijun Huang, Wenting Peng
•
With the proposal of the concept of “metagenomics” and the development of sequencing technology, 16S rRNA gene profiling has been widely applied in the survey of microbial diversity. This study explored the gut microbiota of children with hand, foot and mouth disease (HFMD). This study investigated the gut microbiota of 24 children with asymptomatic and symptomatic hand, foot, and mouth disease (HFMD) and 19 healthy controls using 16S rRNA sequencing. The gut microbiota, both in asymptomatic and symptomatic HFMD patients, was distinct from the controls, with the composition of gut microbiota in the HFMD cases represented a significant difference. The dysbiosis of gut microbiota of the HFMD cases included a reduction of butyrate-producing bacteria and an up-regulation of inflammation-inducing bacteria. These may have impaired the intestinal biological mucosal barrier and host immune functions, promoting the invasion of the enterovirus.
{"title":"Evaluation of gut microbial diversity and correlation in asymptomatic and symptomatic patients with hand, foot and mouth disease","authors":"Hongwei Jin , Bin Feng , Wenxiao Gong, Xiaoliang Chen, Dongli Wang, Yan Li, Weijun Huang, Wenting Peng","doi":"10.1016/j.ygeno.2025.111126","DOIUrl":"10.1016/j.ygeno.2025.111126","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>With the proposal of the concept of “metagenomics” and the development of sequencing technology, 16S rRNA gene profiling has been widely applied in the survey of microbial diversity. This study explored the gut microbiota of children with hand, foot and mouth disease (HFMD). This study investigated the gut microbiota of 24 children with asymptomatic and symptomatic hand, foot, and mouth disease (HFMD) and 19 healthy controls using 16S rRNA sequencing. The gut microbiota, both in asymptomatic and symptomatic HFMD patients, was distinct from the controls, with the composition of gut microbiota in the HFMD cases represented a significant difference. The dysbiosis of gut microbiota of the HFMD cases included a reduction of butyrate-producing bacteria and an up-regulation of inflammation-inducing bacteria. These may have impaired the intestinal biological mucosal barrier and host immune functions, promoting the invasion of the enterovirus.</div></span></li></ul></div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111126"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Idiopathic congenital nystagmus (ICN) is characterized by involuntary horizontal eye oscillations and is frequently associated with X-linked FRMD7 mutations. Despite over 150 FRMD7 variants have been reported, their pathogenic mechanisms remain poorly understood. In this study, we identified a novel FRMD7 deletion (c.742-211_1050+59del p.Leu249_Val351del) in an ICN-affected family. Minigenes analysis demonstrated that this FRMD7 mutation caused skipping of exon 9– 11. RT-qPCR and western blotting revealed unchanged FRMD7 mRNA levels but a significantly upregulated in protein expression. Structural modeling indicated the loss of a crucial amino acid segment in the mutated FRMD7 protein (FRMD7-m1). These findings suggest that this FRMD7 deletion disrupts protein translation and stability, contributing to ICN pathogenesis, and expand our understanding of FRMD7-related molecular mechanisms.
{"title":"Functional analysis of a novel segment deletion in the FRMD7 gene causing X-linked idiopathic congenital nystagmus","authors":"Xiaoli Zhao , Xinyang Li , Jian Yuan, Xiaolei Wang, Qinxue Meng, Xinwen Zhang","doi":"10.1016/j.ygeno.2025.111138","DOIUrl":"10.1016/j.ygeno.2025.111138","url":null,"abstract":"<div><div>Idiopathic congenital nystagmus (ICN) is characterized by involuntary horizontal eye oscillations and is frequently associated with X-linked <em>FRMD7</em> mutations. Despite over 150 <em>FRMD7</em> variants have been reported, their pathogenic mechanisms remain poorly understood. In this study, we identified a novel <em>FRMD7</em> deletion (c.742-211_1050+59del p.Leu249_Val351del) in an ICN-affected family. Minigenes analysis demonstrated that this <em>FRMD7</em> mutation caused skipping of exon 9– 11. RT-qPCR and western blotting revealed unchanged <em>FRMD7</em> mRNA levels but a significantly upregulated in protein expression. Structural modeling indicated the loss of a crucial amino acid segment in the mutated FRMD7 protein (<em>FRMD7</em>-m1). These findings suggest that this <em>FRMD7</em> deletion disrupts protein translation and stability, contributing to ICN pathogenesis, and expand our understanding of <em>FRMD7</em>-related molecular mechanisms.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111138"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-21DOI: 10.1016/j.ygeno.2025.111115
Zhenzhen Pan , Cengceng He , Xuena Xu , Yuting Jin , Mingyi Xu , Suwan Xiong , Ling Li , Chuangli Hao
Background
Obese asthma is a specific phenotype of childhood asthma characterized by increased severity, decreased quality of life, and reduced treatment response. Herein, we applied transcriptomics to investigate biomarkers of obese asthma.
Methods
Mouse models of obesity and asthma were induced through high-fat diet (HFD) feeding and ovalbumin inhalation, respectively. RNA was extracted from lung samples from HFD-fed asthma, HFD-fed control, normal-fat diet (NFD)-fed asthma, and NFD-fed control mice. Transcriptome sequencing data were analyzed for quality control (QC), and differentially expressed genes (DEGs) were identified. From this list, candidate genes were obtained through intersections, followed by the construction of protein-protein interaction (PPI) networks to identify key genes. Subsequently, immune cell infiltration was analyzed across the different subgroups. Key genes were validated using Quantitative Polymerase Chain Reaction (PCR).
Results
Overall, 86 candidate genes were identified from the intersection of different DEG sets. PPI networks were constructed using three algorithms, revealing nine key genes (ITGM, Slc11a1, Nos2, PirB, IL1RN, LCN2, CD33, MSR1, and CXCL2). Immune infiltration analysis revealed distinct responses in immune cells, including naïve B cells and plasma cells. Following verification by qPCR, ITGAM, Nos2, LCN2, CD33, MSR1, and CXCL2 were confirmed to be significantly higher in the HFD-fed asthma group than in the NFD-fed asthma group. Slc11a1 was significantly downregulated, while PirB and IL1RN showed no significant differences. The expression levels of ITGAM, Nos2, and LCN2 demonstrated a consistent trend in human peripheral blood samples. However, to further substantiate their roles in obesity-associated asthma, an expanded sample size is required for confirmation.
Conclusion
This study systematically investigated the molecular mechanisms underlying the associated obesity and metabolic disorders, identified biomarkers, and provided new directions for future therapeutic and clinical studies on obese asthma.
{"title":"Exploration of novel biomarkers of obese asthma using RNA sequencing in high-fat-fed asthmatic model mice","authors":"Zhenzhen Pan , Cengceng He , Xuena Xu , Yuting Jin , Mingyi Xu , Suwan Xiong , Ling Li , Chuangli Hao","doi":"10.1016/j.ygeno.2025.111115","DOIUrl":"10.1016/j.ygeno.2025.111115","url":null,"abstract":"<div><h3>Background</h3><div>Obese asthma is a specific phenotype of childhood asthma characterized by increased severity, decreased quality of life, and reduced treatment response. Herein, we applied transcriptomics to investigate biomarkers of obese asthma.</div></div><div><h3>Methods</h3><div>Mouse models of obesity and asthma were induced through high-fat diet (HFD) feeding and ovalbumin inhalation, respectively. RNA was extracted from lung samples from HFD-fed asthma, HFD-fed control, normal-fat diet (NFD)-fed asthma, and NFD-fed control mice. Transcriptome sequencing data were analyzed for quality control (QC), and differentially expressed genes (DEGs) were identified. From this list, candidate genes were obtained through intersections, followed by the construction of protein-protein interaction (PPI) networks to identify key genes. Subsequently, immune cell infiltration was analyzed across the different subgroups. Key genes were validated using Quantitative Polymerase Chain Reaction (PCR).</div></div><div><h3>Results</h3><div>Overall, 86 candidate genes were identified from the intersection of different DEG sets. PPI networks were constructed using three algorithms, revealing nine key genes (ITGM, Slc11a1, Nos2, PirB, IL1RN, LCN2, CD33, MSR1, and CXCL2). Immune infiltration analysis revealed distinct responses in immune cells, including naïve B cells and plasma cells. Following verification by qPCR, ITGAM, Nos2, LCN2, CD33, MSR1, and CXCL2 were confirmed to be significantly higher in the HFD-fed asthma group than in the NFD-fed asthma group. Slc11a1 was significantly downregulated, while PirB and IL1RN showed no significant differences. The expression levels of ITGAM, Nos2, and LCN2 demonstrated a consistent trend in human peripheral blood samples. However, to further substantiate their roles in obesity-associated asthma, an expanded sample size is required for confirmation.</div></div><div><h3>Conclusion</h3><div>This study systematically investigated the molecular mechanisms underlying the associated obesity and metabolic disorders, identified biomarkers, and provided new directions for future therapeutic and clinical studies on obese asthma.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111115"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-30DOI: 10.1016/j.ygeno.2025.111128
Shanshan Gao , Mengyi Guo , Enlu Zhang , Zupei Yi , Kui Liu , Shuang Xue , Ruimin Li , Kunpeng Zhang
Aldehyde oxidase in insects participates in the degradation of various aldehyde insecticides and toxic plant-derived aldehydes, increasing the resistance of pests to these agents. However, the specific mechanism underlying this resistance remains unclear. In this study, we examined the differentially expressed genes in Tribolium castaneum, a global stored-grain pest, before and after knockdown of aldehyde oxidase TcAOX3. We found decreased expression levels of chymotrypsin-like proteinase 5B precursor and serine protease P40, which are involved in immunity and digestion, indicating that TcAOX3 may be involved in immune and digestive functions of larvae. Reduction of TcAOX3 expression also significantly decreased the resistance of T. castaneum larvae to benzaldehyde, with an increase of about 20 % in the killing effect of benzaldehyde against T. castaneum. Molecular docking and isothermal titration calorimetry results showed that benzaldehyde bound to TcAOX3 via Val761, Tyr558, Met562, Ile559, Gln557, Arg763, and Arg762, with a binding energy of ΔG = −24.23 kJ/mol. These results provide a theoretical basis for analysis of the detoxification mechanism of aldehyde oxidase in insects and offer a reference for screening of green insecticides targeting aldehyde oxidase.
{"title":"RNA-seq analysis combined with insecticidal efficacy assays reveal the insecticidal molecular mechanism of benzaldehyde against Tribolium castaneum","authors":"Shanshan Gao , Mengyi Guo , Enlu Zhang , Zupei Yi , Kui Liu , Shuang Xue , Ruimin Li , Kunpeng Zhang","doi":"10.1016/j.ygeno.2025.111128","DOIUrl":"10.1016/j.ygeno.2025.111128","url":null,"abstract":"<div><div>Aldehyde oxidase in insects participates in the degradation of various aldehyde insecticides and toxic plant-derived aldehydes, increasing the resistance of pests to these agents. However, the specific mechanism underlying this resistance remains unclear. In this study, we examined the differentially expressed genes in <em>Tribolium castaneum</em>, a global stored-grain pest, before and after knockdown of aldehyde oxidase <em>TcAOX3</em>. We found decreased expression levels of chymotrypsin-like proteinase 5B precursor and serine protease P40, which are involved in immunity and digestion, indicating that <em>TcAOX3</em> may be involved in immune and digestive functions of larvae. Reduction of <em>TcAOX3</em> expression also significantly decreased the resistance of <em>T. castaneum</em> larvae to benzaldehyde, with an increase of about 20 % in the killing effect of benzaldehyde against <em>T. castaneum</em>. Molecular docking and isothermal titration calorimetry results showed that benzaldehyde bound to TcAOX3 via Val761, Tyr558, Met562, Ile559, Gln557, Arg763, and Arg762, with a binding energy of ΔG = −24.23 kJ/mol. These results provide a theoretical basis for analysis of the detoxification mechanism of aldehyde oxidase in insects and offer a reference for screening of green insecticides targeting aldehyde oxidase.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111128"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-30DOI: 10.1016/j.ygeno.2025.111116
Pengwei Hu , Jixiang Xing , Wuritu Yang , Hongxia Chi , Yongqiang Xing , Yongchun Zuo
Alternative splicing (AS) in single cell is crucial for cell heterogeneity, gene expression and transcriptome diversity. However, given the complexity of AS analysis in single-cell RNA sequencing (scRNA-seq), employing a continuous and iterative process to refine data and uncover relevant latent information is crucial. While several tools have been developed to address various aspects of scRNA-seq AS analysis, a versatile and user-friendly web application that can perform all essential steps of AS analysis on scRNA-seq data is still lacking. Here, we made significant advancements in improving the usability and functionality of MARVEL. Firstly, we developed a Python package that can easily and efficiently generate input files, reducing the technical barrier. Secondly, we developed a Shiny-based R package that extends MARVEL's analysis capabilities to multiple cell populations, enabling interactive, code-free ex-ploration of AS and gene expression dynamics at single-cell level. The package, named ScASplicer (Single-Cell Alternative Splicing Shiny Explorer), provides a user-friendly platform for more efficient and comprehensive single-cell AS analysis.
单细胞的选择性剪接（AS）对细胞异质性、基因表达和转录组多样性至关重要。然而，考虑到单细胞RNA测序（scRNA-seq）中AS分析的复杂性，采用连续迭代的过程来完善数据并发现相关的潜在信息至关重要。虽然已经开发了一些工具来解决scRNA-seq AS分析的各个方面，但仍然缺乏一个通用的、用户友好的web应用程序，可以在scRNA-seq数据上执行AS分析的所有基本步骤。在这里，我们在提高MARVEL的可用性和功能方面取得了重大进展。首先，我们开发了一个Python包，它可以轻松有效地生成输入文件，减少了技术障碍。其次，我们开发了一个基于shine的R包，将MARVEL的分析能力扩展到多个细胞群体，从而实现了在单细胞水平上对AS和基因表达动态的交互式、无代码探索。该软件包名为ScASplicer (Single-Cell Alternative Splicing Shiny Explorer)，为更高效和全面的单细胞AS分析提供了一个用户友好的平台。
{"title":"ScASplicer: An interactive shiny/R application for alternative splicing analysis of single-cell sequencing","authors":"Pengwei Hu , Jixiang Xing , Wuritu Yang , Hongxia Chi , Yongqiang Xing , Yongchun Zuo","doi":"10.1016/j.ygeno.2025.111116","DOIUrl":"10.1016/j.ygeno.2025.111116","url":null,"abstract":"<div><div>Alternative splicing (AS) in single cell is crucial for cell heterogeneity, gene expression and transcriptome diversity. However, given the complexity of AS analysis in single-cell RNA sequencing (scRNA-seq), employing a continuous and iterative process to refine data and uncover relevant latent information is crucial. While several tools have been developed to address various aspects of scRNA-seq AS analysis, a versatile and user-friendly web application that can perform all essential steps of AS analysis on scRNA-seq data is still lacking. Here, we made significant advancements in improving the usability and functionality of MARVEL. Firstly, we developed a Python package that can easily and efficiently generate input files, reducing the technical barrier. Secondly, we developed a Shiny-based R package that extends MARVEL's analysis capabilities to multiple cell populations, enabling interactive, code-free ex-ploration of AS and gene expression dynamics at single-cell level. The package, named ScASplicer (Single-Cell Alternative Splicing Shiny Explorer), provides a user-friendly platform for more efficient and comprehensive single-cell AS analysis.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111116"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-30DOI: 10.1016/j.ygeno.2025.111119
Huihan Ai , Hang Yang , Chai Luv , Guanglong Chen , Weijie Zhao , Zikun Wu , Shijun Xu , Jie Ma , Kangdong Liu , Zhi Li
Background
Typical cases of familial adenomatous polyposis (FAP) exhibit variants in the coding sequence of adenomatous polyposis coli (APC) gene coding sequence. Families without detectable APC variants can't benefit from genetic testing.
Methods
We investigated a FAP family with APC variant negativity using exome sequencing, genome sequencing. Quantitative real-time PCR, single nucleotide polymorphism analysis, sanger sequencing, and organoid drug sensitivity assays.
Results
We discovered a novel deletion spanning about 100 kb upstream of the APC transcription start site, covering the entire APC 1B promoter, in all affected members of the FAP family. The proband's blood RNA revealed the silencing of one APC allele, linked to this deletion. This deletion suppressed APC gene transcription. Additionally, this family exhibited unique extracolonic manifestations, and their response to FAP treatment drugs was similar to that of typical FAP cases. Despite this, conventional anticancer treatments led to favorable outcomes for the patients.
Conclusion
These findings indicated that APC exon variant-negative FAP patients may have deletions in the promoter region, particularly the 1B region. Their clinical features and treatment responses differ from other FAP cases, emphasizing the importance of personalized management strategies tailored to their variant profile.
{"title":"Identifying and characterizing a novel APC promoter 1B deletion in a Chinese family with familial adenomatous polyposis","authors":"Huihan Ai , Hang Yang , Chai Luv , Guanglong Chen , Weijie Zhao , Zikun Wu , Shijun Xu , Jie Ma , Kangdong Liu , Zhi Li","doi":"10.1016/j.ygeno.2025.111119","DOIUrl":"10.1016/j.ygeno.2025.111119","url":null,"abstract":"<div><h3>Background</h3><div>Typical cases of familial adenomatous polyposis (FAP) exhibit variants in the coding sequence of adenomatous polyposis coli (<em>APC</em>) gene coding sequence. Families without detectable APC variants can't benefit from genetic testing.</div></div><div><h3>Methods</h3><div>We investigated a FAP family with APC variant negativity using exome sequencing, genome sequencing. Quantitative real-time PCR, single nucleotide polymorphism analysis, sanger sequencing, and organoid drug sensitivity assays.</div></div><div><h3>Results</h3><div>We discovered a novel deletion spanning about 100 kb upstream of the APC transcription start site, covering the entire <em>APC</em> 1B promoter, in all affected members of the FAP family. The proband's blood RNA revealed the silencing of one APC allele, linked to this deletion. This deletion suppressed <em>APC</em> gene transcription. Additionally, this family exhibited unique extracolonic manifestations, and their response to FAP treatment drugs was similar to that of typical FAP cases. Despite this, conventional anticancer treatments led to favorable outcomes for the patients.</div></div><div><h3>Conclusion</h3><div>These findings indicated that <em>APC</em> exon variant-negative FAP patients may have deletions in the promoter region, particularly the 1B region. Their clinical features and treatment responses differ from other FAP cases, emphasizing the importance of personalized management strategies tailored to their variant profile.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111119"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-30DOI: 10.1016/j.ygeno.2025.111120
Songyi Ye , Chenyu Wu , Shuaijing Huang , Haowen Fan , Zhiqing Zhang , Jinling Chen , Wenliang Ge
Cryptorchidism, affecting 1 %–9 % of male neonates, represents one of the most prevalent congenital genitourinary anomalies. Studies highlighted Leydig cell derived insulin-like 3 (Insl3) as pivotal in the initial phase of testicular descent. However, the pathogenic mechanisms underlying decreased Insl3 remain poorly elucidated. Here, we showed that triggering receptor expressed on myeloid cells-2 (Trem2) acted as a central mediator in macrophage-Leydig cell communication, influencing testicular descent via Insl3 regulation. In boys with cryptorchidism, Trem2 in testes was markedly downregulated. 63.16 % of Trem2−/− mice exhibited cryptorchidism and abnormal sperm motility and morphology, concomitant with decreased Leydig cells and Insl3. In vitro studies using human testicular cultures also revealed that Trem2 expression positively correlated with Insl3 expression. Mechanistically, ketoconazole elevated TNF-α due to suppression of the Trem2-Dap12-Syk-PI3K axis, ultimately disrupting total Leydig cell number and Insl3 expression. Collectively, these findings unveil Trem2 as a paracrine sentinel for Insl3-dependent testicular descent, thereby mitigating cryptorchidism.
{"title":"Trem2-dependent Insl3 regulation via Dap12-Syk-PI3K pathway: A new pathogenic mechanism in cryptorchidism","authors":"Songyi Ye , Chenyu Wu , Shuaijing Huang , Haowen Fan , Zhiqing Zhang , Jinling Chen , Wenliang Ge","doi":"10.1016/j.ygeno.2025.111120","DOIUrl":"10.1016/j.ygeno.2025.111120","url":null,"abstract":"<div><div>Cryptorchidism, affecting 1 %–9 % of male neonates, represents one of the most prevalent congenital genitourinary anomalies. Studies highlighted Leydig cell derived insulin-like 3 (Insl3) as pivotal in the initial phase of testicular descent. However, the pathogenic mechanisms underlying decreased Insl3 remain poorly elucidated. Here, we showed that triggering receptor expressed on myeloid cells-2 (Trem2) acted as a central mediator in macrophage-Leydig cell communication, influencing testicular descent <em>via</em> Insl3 regulation. In boys with cryptorchidism, Trem2 in testes was markedly downregulated. 63.16 % of <em>Trem2</em><sup>−/−</sup> mice exhibited cryptorchidism and abnormal sperm motility and morphology, concomitant with decreased Leydig cells and Insl3. <em>In vitro</em> studies using human testicular cultures also revealed that Trem2 expression positively correlated with Insl3 expression. Mechanistically, ketoconazole elevated TNF-α due to suppression of the Trem2-Dap12-Syk-PI3K axis, ultimately disrupting total Leydig cell number and Insl3 expression. Collectively, these findings unveil Trem2 as a paracrine sentinel for Insl3-dependent testicular descent, thereby mitigating cryptorchidism.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111120"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-10DOI: 10.1016/j.ygeno.2025.111108
Daniil Ruvinskiy , Kisun Pokharel , Rodney Okwasiimire , Rayner Gonzalez-Prendes , Catarina Ginja , Nasser Ghanem , Donald R. Kugonza , Mahlako L. Makgahlela , Heli Lindeberg , Melak Weldenegodguad , Juha Kantanen , Martijn Derks , Richard P.M.A. Crooijmans
Climate change is impacting the global spread of infectious diseases, altering pathogen distribution and transmission, and threatening human and animal health. This study investigates the presence of potential pathogens in blood within unmapped reads obtained from whole-genome sequencing (WGS) data of various cattle breeds across geographically diverse regions, including South Africa, Uganda, Egypt, Portugal, The Netherlands, and Finland. Unmapped reads were extracted, assembled into contigs, and subjected to taxonomic analysis based on an extensive literature search. The analysis revealed significant geographic variation in pathogen composition, with breeds in the Southern Hemisphere (Uganda, Egypt, and South Africa) showing higher pathogen alignment counts while Northern breeds (particularly from Finland) exhibited lower diversity and counts. Portugal, representing a transition zone, exhibited a higher burden of parasites and tick-borne related pathogens than their Northern counterparts, which were also prevalent in Southern Hemisphere breeds such as Theileria parva, Anaplasma platys, Theileria orientalis, and Babesia bigemina, which is in line with the known capacity of these breeds to cope with local pathogens. Dutch breeds were found to harbor Escherichia coli O157, a known public health concern. The study provided key insights into emerging disease risks influenced by climate change and livestock management practices, but also on the need to investigate possible adaptive responses underlying disease resistance in some breeds. This study highlights the potential for climate-driven variations in disease ecology and transmission, emphasizing the need for integrating genomic and environmental data, and is currently the most comprehensive study to date investigating the microbial diversity present in unmapped reads obtained from WGS data of cattle populations.
{"title":"Unmapped reads from whole-genome sequencing data reveal pathogen diversity in European and African cattle breeds","authors":"Daniil Ruvinskiy , Kisun Pokharel , Rodney Okwasiimire , Rayner Gonzalez-Prendes , Catarina Ginja , Nasser Ghanem , Donald R. Kugonza , Mahlako L. Makgahlela , Heli Lindeberg , Melak Weldenegodguad , Juha Kantanen , Martijn Derks , Richard P.M.A. Crooijmans","doi":"10.1016/j.ygeno.2025.111108","DOIUrl":"10.1016/j.ygeno.2025.111108","url":null,"abstract":"<div><div>Climate change is impacting the global spread of infectious diseases, altering pathogen distribution and transmission, and threatening human and animal health. This study investigates the presence of potential pathogens in blood within unmapped reads obtained from whole-genome sequencing (WGS) data of various cattle breeds across geographically diverse regions, including South Africa, Uganda, Egypt, Portugal, The Netherlands, and Finland. Unmapped reads were extracted, assembled into contigs, and subjected to taxonomic analysis based on an extensive literature search. The analysis revealed significant geographic variation in pathogen composition, with breeds in the Southern Hemisphere (Uganda, Egypt, and South Africa) showing higher pathogen alignment counts while Northern breeds (particularly from Finland) exhibited lower diversity and counts. Portugal, representing a transition zone, exhibited a higher burden of parasites and tick-borne related pathogens than their Northern counterparts, which were also prevalent in Southern Hemisphere breeds such as <em>Theileria parva</em>, <em>Anaplasma platys</em>, <em>Theileria orientalis</em>, and <em>Babesia bigemina,</em> which is in line with the known capacity of these breeds to cope with local pathogens. Dutch breeds were found to harbor <em>Escherichia coli O157</em>, a known public health concern. The study provided key insights into emerging disease risks influenced by climate change and livestock management practices, but also on the need to investigate possible adaptive responses underlying disease resistance in some breeds. This study highlights the potential for climate-driven variations in disease ecology and transmission, emphasizing the need for integrating genomic and environmental data, and is currently the most comprehensive study to date investigating the microbial diversity present in unmapped reads obtained from WGS data of cattle populations.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111108"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-10DOI: 10.1016/j.ygeno.2025.111106
Nan Yang , Shiqun Sun , Xiantao Chen , Tongtong Yan , Nan Gu , Zhihui Liu
Background and objectives
Periodontitis(PD) is a chronic inflammatory disease that poses a serious threat to oral health and is one of the risk factors for atherosclerosis(AS). A growing body of evidence suggests that the two diseases are closely related. However, current studies have yet to fully understand the common genes and common mechanisms between PD and AS. This study aimed to screen the tandem genes of PD and AS and the potential relationship between the tandem genes and pan-apoptosis-related genes. By analyzing the relationship between the core genes and immune cells, it will provide new targets for clinical treatment.
Materials and methods
The PD and AS datasets were downloaded from the GEO database and differential expression analysis was performed to obtain DEGs. AS-related genes were downloaded from the GeneCards database, and PANoptosis-related genes were obtained through literature review. AS-related genes were merged into AS DEGs, and overlapping DEGs were cross-talk genes for PD and AS. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Pearson coefficients were used to calculate the correlation between cross-talk genes and PANoptosis-related genes in the PD and AS datasets. The intersection of cross-talk genes and PANoptosis-related genes was defined as cross-talk-PANoptosis genes. Core genes were screened using ROC analysis and XGBoost. PPI sub-network, gene-biological processes and gene-pathway networks were constructed based on the core genes. In addition, immune infiltration on the PD and AS datasets was analyzed using the CIBERSORT algorithm.
Results
285 cross-talk genes overlapped between PD DEGs and AS DEGs. The intersection of cross-talk genes with 109 PANoptosis-related genes was defined as cross-talk-PAoptosis genes. ROC and XGBoost showed that MLKL, ZBP1, CD14, and IL6 were more accurate than the other cross-talk-PAoptosis genes in predicting the diseases, and were better in terms of the overall characteristics. GO and KEGG analyses showed that these four core genes were involved in the immune and inflammatory response of the organism. The results of immune infiltration showed that Monocytes and Mast cells resting were altered to a greater extent in PD and AS patients. Finally, 24 drugs related to the core genes were retrieved from the DGIDB database.
Conclusions
This study reveals the joint mechanism between PD and AS associated with PANoptosis. Analyzing the four core genes and immune cells may provide new therapeutic directions for the pathogenesis of PD combined with AS.
{"title":"Identification of cross-talk pathways and PANoptosis-related genes in periodontitis and atherosclerosis by bioinformatics analysis and machine learning","authors":"Nan Yang , Shiqun Sun , Xiantao Chen , Tongtong Yan , Nan Gu , Zhihui Liu","doi":"10.1016/j.ygeno.2025.111106","DOIUrl":"10.1016/j.ygeno.2025.111106","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Periodontitis(PD) is a chronic inflammatory disease that poses a serious threat to oral health and is one of the risk factors for atherosclerosis(AS). A growing body of evidence suggests that the two diseases are closely related. However, current studies have yet to fully understand the common genes and common mechanisms between PD and AS. This study aimed to screen the tandem genes of PD and AS and the potential relationship between the tandem genes and pan-apoptosis-related genes. By analyzing the relationship between the core genes and immune cells, it will provide new targets for clinical treatment.</div></div><div><h3>Materials and methods</h3><div>The PD and AS datasets were downloaded from the GEO database and differential expression analysis was performed to obtain DEGs. AS-related genes were downloaded from the GeneCards database, and PANoptosis-related genes were obtained through literature review. AS-related genes were merged into AS DEGs, and overlapping DEGs were cross-talk genes for PD and AS. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Pearson coefficients were used to calculate the correlation between cross-talk genes and PANoptosis-related genes in the PD and AS datasets. The intersection of cross-talk genes and PANoptosis-related genes was defined as cross-talk-PANoptosis genes. Core genes were screened using ROC analysis and XGBoost. PPI sub-network, gene-biological processes and gene-pathway networks were constructed based on the core genes. In addition, immune infiltration on the PD and AS datasets was analyzed using the CIBERSORT algorithm.</div></div><div><h3>Results</h3><div>285 cross-talk genes overlapped between PD DEGs and AS DEGs. The intersection of cross-talk genes with 109 PANoptosis-related genes was defined as cross-talk-PAoptosis genes. ROC and XGBoost showed that MLKL, ZBP1, CD14, and IL6 were more accurate than the other cross-talk-PAoptosis genes in predicting the diseases, and were better in terms of the overall characteristics. GO and KEGG analyses showed that these four core genes were involved in the immune and inflammatory response of the organism. The results of immune infiltration showed that Monocytes and Mast cells resting were altered to a greater extent in PD and AS patients. Finally, 24 drugs related to the core genes were retrieved from the DGIDB database.</div></div><div><h3>Conclusions</h3><div>This study reveals the joint mechanism between PD and AS associated with PANoptosis. Analyzing the four core genes and immune cells may provide new therapeutic directions for the pathogenesis of PD combined with AS.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111106"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-10-11DOI: 10.1016/j.ygeno.2025.111136
Guangyi Chen , Junhui Zhang , Jiayi Wang , Wenxiu Chen , Haoran Li , Haoran Su , Shaoyi Dai , Yumei Tao , Yunxia Cao , Qiang Hong , Fenfen Xie
Liver lipid disorders are common in polycystic ovary syndrome (PCOS) patients. A DHEA-induced PCOS mouse model exhibited elevated liver triglyceride (TG) and total cholesterol (TC), reinforcing this association between liver lipids and PCOS. Liver transcriptomic sequencing revealed that 168 differentially expressed genes and 285 alternative splicing (AS) event genes, significantly enriching retinol metabolism. Further combined analyses showed the Cyp4a32 and Hsd17b6 genes were abnormally expressed in the livers of PCOS mice. AS analysis revealed that Cyp4a32 had upregulated exon skipping (SE), including SE and mutually exclusive exons (MXE), while among the modes of SE, MXE, and alternative 3′ splice site (A3SS), Hsd17b6 showed downregulated MXE. These findings suggest that Cyp4a32 and Hsd17b6 may change the retinol metabolism by modulating AS patterns, which then dysregulate hepatic lipid metabolism in PCOS. This study highlights potential therapeutic targets for PCOS-associated liver lipid disorders.
{"title":"Regulation of alternative splicing of retinol metabolism in lipid abnormality of PCOS liver by Cyp4a32 and Hsd17b6","authors":"Guangyi Chen , Junhui Zhang , Jiayi Wang , Wenxiu Chen , Haoran Li , Haoran Su , Shaoyi Dai , Yumei Tao , Yunxia Cao , Qiang Hong , Fenfen Xie","doi":"10.1016/j.ygeno.2025.111136","DOIUrl":"10.1016/j.ygeno.2025.111136","url":null,"abstract":"<div><div>Liver lipid disorders are common in polycystic ovary syndrome (PCOS) patients. A DHEA-induced PCOS mouse model exhibited elevated liver triglyceride (TG) and total cholesterol (TC), reinforcing this association between liver lipids and PCOS. Liver transcriptomic sequencing revealed that 168 differentially expressed genes and 285 alternative splicing (AS) event genes, significantly enriching retinol metabolism. Further combined analyses showed the Cyp4a32 and Hsd17b6 genes were abnormally expressed in the livers of PCOS mice. AS analysis revealed that Cyp4a32 had upregulated exon skipping (SE), including SE and mutually exclusive exons (MXE), while among the modes of SE, MXE, and alternative 3′ splice site (A3SS), Hsd17b6 showed downregulated MXE. These findings suggest that Cyp4a32 and Hsd17b6 may change the retinol metabolism by modulating AS patterns, which then dysregulate hepatic lipid metabolism in PCOS. This study highlights potential therapeutic targets for PCOS-associated liver lipid disorders.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111136"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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