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ScASplicer: An interactive shiny/R application for alternative splicing analysis of single-cell sequencing ScASplicer:用于单细胞测序的选择性剪接分析的交互式闪亮/R应用程序。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-30 DOI: 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。
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引用次数: 0
Identifying and characterizing a novel APC promoter 1B deletion in a Chinese family with familial adenomatous polyposis 中国家族性腺瘤性息肉病家族中APC启动子1B缺失的鉴定和特征
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-30 DOI: 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.
背景:家族性腺瘤性息肉病(FAP)的典型病例表现为大肠腺瘤性息肉病(APC)基因编码序列的变异。没有检测到APC变异的家庭不能从基因检测中获益。方法:采用外显子组测序、全基因组测序对APC变异阴性的FAP家族进行研究。实时定量PCR、单核苷酸多态性分析、sanger测序和类器官药物敏感性分析。结果:在所有受影响的FAP家族成员中,我们发现了APC转录起始位点上游约100 kb的新缺失,覆盖了整个APC 1B启动子。先证者的血液RNA显示一个APC等位基因沉默,与这种缺失有关。这种缺失抑制了APC基因的转录。此外,该家族表现出独特的结肠外表现,其对FAP治疗药物的反应与典型FAP病例相似。尽管如此,传统的抗癌治疗对患者还是有良好的效果。结论:这些发现表明APC外显子变异阴性的FAP患者可能在启动子区域,特别是1B区域存在缺失。他们的临床特征和治疗反应与其他FAP病例不同,强调了针对其不同情况量身定制个性化管理策略的重要性。
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引用次数: 0
Trem2-dependent Insl3 regulation via Dap12-Syk-PI3K pathway: A new pathogenic mechanism in cryptorchidism 通过Dap12-Syk-PI3K途径调控trem2依赖性Insl3:隐睾的一种新的致病机制
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-30 DOI: 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.
隐睾,影响1 %-9 %的男性新生儿,是最普遍的先天性泌尿生殖系统异常之一。研究强调,间质细胞衍生的胰岛素样3 (Insl3)在睾丸下降的初始阶段起关键作用。然而,Insl3降低的致病机制尚不清楚。在这里,我们发现骨髓细胞上表达的触发受体-2 (Trem2)在巨噬细胞-间质细胞通讯中起中心介质作用,通过Insl3调节影响睾丸下降。在隐睾男孩中,睾丸中的Trem2明显下调。63.16 %的Trem2-/-小鼠出现隐睾、精子运动和形态异常,并伴有间质细胞和Insl3的减少。体外对人睾丸培养物的研究也显示Trem2的表达与Insl3的表达呈正相关。从机制上讲,酮康唑通过抑制Trem2-Dap12-Syk-PI3K轴而升高TNF-α,最终破坏间质细胞总数和Insl3表达。总的来说,这些发现揭示了Trem2作为insl3依赖性睾丸下降的旁分泌前哨,从而减轻了隐睾。
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引用次数: 0
Unmapped reads from whole-genome sequencing data reveal pathogen diversity in European and African cattle breeds 全基因组测序数据的未映射读取揭示了欧洲和非洲牛品种的病原体多样性。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-10 DOI: 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.
气候变化正在影响传染病的全球传播,改变病原体的分布和传播,并威胁人类和动物的健康。本研究调查了来自不同地理区域(包括南非、乌干达、埃及、葡萄牙、荷兰和芬兰)的各种牛品种的全基因组测序数据中未映射读取的血液中潜在病原体的存在。提取未映射的reads,组装成contigs,并在广泛的文献检索的基础上进行分类分析。分析显示,病原体组成存在显著的地理差异,南半球(乌干达、埃及和南非)的品种显示出较高的同源病原体计数,而北部品种(特别是来自芬兰的品种)的多样性和计数较低。葡萄牙是一个过渡区,其寄生虫和蜱传相关病原体的负担比其北部地区更高,而南半球品种如细小芽孢杆菌、扁平无原体、东方芽孢杆菌和双巴贝斯虫也普遍存在,这与这些品种应对当地病原体的已知能力相符。荷兰品种被发现含有大肠杆菌O157,这是一个已知的公共卫生问题。这项研究提供了关于受气候变化和牲畜管理实践影响的新出现疾病风险的关键见解,而且还提供了调查某些品种抗病基础上可能的适应性反应的必要性。该研究强调了气候驱动的疾病生态和传播变化的可能性,强调了整合基因组和环境数据的必要性,并且是迄今为止最全面的研究,调查了从牛种群WGS数据中获得的未定位reads中存在的微生物多样性。
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引用次数: 0
Identification of cross-talk pathways and PANoptosis-related genes in periodontitis and atherosclerosis by bioinformatics analysis and machine learning 通过生物信息学分析和机器学习鉴定牙周炎和动脉粥样硬化的串音通路和panoptosis相关基因
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-10 DOI: 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.
背景与目的牙周炎(periodontitis, PD)是一种严重威胁口腔健康的慢性炎症性疾病,是动脉粥样硬化(AS)的危险因素之一。越来越多的证据表明这两种疾病密切相关。然而,目前的研究尚未完全了解PD和AS之间的共同基因和共同机制。本研究旨在筛选PD和AS的串联基因,以及串联基因与泛凋亡相关基因之间的潜在关系。通过分析核心基因与免疫细胞的关系,将为临床治疗提供新的靶点。材料和方法从GEO数据库中下载PD和AS数据集,进行差异表达分析,获得deg。从GeneCards数据库下载as相关基因,通过文献查阅获得panoptosis相关基因。将AS相关基因合并为AS deg,重叠deg为PD与AS的串扰基因。利用STRING数据库和Cytoscape软件构建蛋白-蛋白相互作用(PPI)网络。使用Pearson系数计算PD和AS数据集中相声基因与panoptosis相关基因之间的相关性。将相声基因与panoptosis相关基因的交集定义为相声- panoptosis基因。采用ROC分析和XGBoost筛选核心基因。以核心基因为基础构建PPI子网络、基因生物学过程和基因通路网络。此外,使用CIBERSORT算法分析PD和AS数据集上的免疫浸润。结果PD - deg与AS - deg间有285个串音基因重叠。将相声基因与109个panoptosis相关基因的交集定义为相声- panoptosis基因。ROC和XGBoost结果显示,MLKL、ZBP1、CD14和IL6在预测疾病方面比其他串音- paoptosis基因更准确,在整体特征方面也更好。GO和KEGG分析表明,这四个核心基因参与了机体的免疫和炎症反应。免疫浸润结果显示,PD和AS患者单核细胞和肥大细胞静息改变程度更大。最后,从DGIDB数据库中检索到与核心基因相关的24种药物。结论本研究揭示了帕金森病与AS合并PANoptosis的联合机制。分析这四个核心基因和免疫细胞可能为PD合并AS的发病机制提供新的治疗方向。
{"title":"Identification of cross-talk pathways and PANoptosis-related genes in periodontitis and atherosclerosis by bioinformatics analysis and machine learning","authors":"Nan Yang ,&nbsp;Shiqun Sun ,&nbsp;Xiantao Chen ,&nbsp;Tongtong Yan ,&nbsp;Nan Gu ,&nbsp;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}
引用次数: 0
Regulation of alternative splicing of retinol metabolism in lipid abnormality of PCOS liver by Cyp4a32 and Hsd17b6 Cyp4a32和Hsd17b6对PCOS肝脏脂质异常中视黄醇代谢的选择性剪接调控。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-10-11 DOI: 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.
肝脏脂质紊乱在多囊卵巢综合征(PCOS)患者中很常见。dhea诱导的PCOS小鼠模型显示肝脏甘油三酯(TG)和总胆固醇(TC)升高,加强了肝脏脂质与PCOS之间的联系。肝脏转录组测序显示,168个差异表达基因和285个选择性剪接(AS)事件基因显著丰富视黄醇代谢。进一步的联合分析显示,Cyp4a32和Hsd17b6基因在PCOS小鼠肝脏中异常表达。AS分析显示Cyp4a32的外显子跳变(SE)上调,包括SE和互斥外显子(MXE),而在SE、MXE和3'剪接位点(A3SS)模式中,Hsd17b6的MXE下调。这些发现表明Cyp4a32和Hsd17b6可能通过调节AS模式改变视黄醇代谢,从而失调PCOS的肝脂质代谢。这项研究强调了pcos相关肝脏脂质紊乱的潜在治疗靶点。
{"title":"Regulation of alternative splicing of retinol metabolism in lipid abnormality of PCOS liver by Cyp4a32 and Hsd17b6","authors":"Guangyi Chen ,&nbsp;Junhui Zhang ,&nbsp;Jiayi Wang ,&nbsp;Wenxiu Chen ,&nbsp;Haoran Li ,&nbsp;Haoran Su ,&nbsp;Shaoyi Dai ,&nbsp;Yumei Tao ,&nbsp;Yunxia Cao ,&nbsp;Qiang Hong ,&nbsp;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}
引用次数: 0
Construction of a genome-wide linkage map and QTL mapping for growth and hypoxia tolerance traits in Chinese longsnout catfish (Leiocassis longirostris) 中国长鼻鲶鱼生长和耐缺氧性状全基因组连锁图谱的构建及QTL定位
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-11-19 DOI: 10.1016/j.ygeno.2025.111157
Fenfei Liang , Zhiru Yang , Wei Liu , Faling Zhang , Xia Liang , Cheng Zhao , Guosong Zhang
The Chinese longsnout catfish (Leiocassis longirostris) is an important freshwater aquaculture species, and the selective breeding of fast-growth and hypoxia tolerance population will have a positive impact on its industry. In order to promote the breeding process of Chinese longsnout catfish, construction of the genetic linkage map and identification of molecular markers associated with fast-growth and hypoxia tolerance is critical for the marker-assisted selection (MAS) of Chinese longsnout catfish. In the present study, whole-genome resequencing was used to construct a high-density genetic linkage map of the Chinese longsnout catfish. The map containing 2946 bin markers was distributed over 26 linkage groups (LGs) with a total genetic coverage of 1980.76 cM and an average density of 0.67 cM. Based on the genetic map, quantitative trait locus (QTL) mapping results suggested that 17 QTLs associated with growth traits and 1 QTL associated with hypoxia tolerance were identified in eight LGs with the phenotypic variability explained (PVE) ranged from 5.1 % to 9.3 %. Four SNP loci from these QTLs were associated with the phenotypic traits validated by Kompetitive Allele Specific PCR or Sanger sequencing. In addition, the expression of three candidate genes for growth traits and five candidate genes for hypoxia tolerance was examined in different growth speed populations and the process of hypoxia exposure and reoxygenation, respectively. The high-density genetic linkage map and QTLs for growth traits and hypoxia tolerance obtained in the present study could further provide the basis for genetic breeding and molecular marker-assisted breeding of Chinese longsnout catfish.
中国长鼻鲶鱼(Leiocassis longirostris)是一种重要的淡水养殖品种,对其快速生长和耐缺氧种群的选育将对其产业产生积极影响。为了促进中国长鼻鲶鱼的育种进程,构建遗传连锁图谱和鉴定与快速生长和耐缺氧相关的分子标记是中国长鼻鲶鱼标记辅助选择(MAS)的关键。本研究采用全基因组重测序技术构建了中国长鼻鲶鱼高密度遗传连锁图谱。该图谱包含2946个标记,分布在26个连锁群(LGs)上,总遗传盖度为1980.76 cM,平均密度为0.67 cM。基于遗传图谱,数量性状位点(QTL)定位结果表明,8个LGs中鉴定出17个与生长性状相关的QTL和1个与耐缺氧相关的QTL,表型变异解释(PVE)范围为5.1% ~ 9.3%。这些qtl中的4个SNP位点与竞争性等位基因特异性PCR或Sanger测序验证的表型性状相关。此外,还检测了3个生长性状候选基因和5个耐缺氧候选基因在不同生长速度群体以及缺氧暴露和再氧化过程中的表达情况。本研究获得的生长性状和耐缺氧性状的高密度遗传连锁图谱和qtl可进一步为中国长鼻鲶鱼的遗传育种和分子标记辅助育种提供依据。
{"title":"Construction of a genome-wide linkage map and QTL mapping for growth and hypoxia tolerance traits in Chinese longsnout catfish (Leiocassis longirostris)","authors":"Fenfei Liang ,&nbsp;Zhiru Yang ,&nbsp;Wei Liu ,&nbsp;Faling Zhang ,&nbsp;Xia Liang ,&nbsp;Cheng Zhao ,&nbsp;Guosong Zhang","doi":"10.1016/j.ygeno.2025.111157","DOIUrl":"10.1016/j.ygeno.2025.111157","url":null,"abstract":"<div><div>The Chinese longsnout catfish (<em>Leiocassis longirostris</em>) is an important freshwater aquaculture species, and the selective breeding of fast-growth and hypoxia tolerance population will have a positive impact on its industry. In order to promote the breeding process of Chinese longsnout catfish, construction of the genetic linkage map and identification of molecular markers associated with fast-growth and hypoxia tolerance is critical for the marker-assisted selection (MAS) of Chinese longsnout catfish. In the present study, whole-genome resequencing was used to construct a high-density genetic linkage map of the Chinese longsnout catfish. The map containing 2946 bin markers was distributed over 26 linkage groups (LGs) with a total genetic coverage of 1980.76 cM and an average density of 0.67 cM. Based on the genetic map, quantitative trait locus (QTL) mapping results suggested that 17 QTLs associated with growth traits and 1 QTL associated with hypoxia tolerance were identified in eight LGs with the phenotypic variability explained (PVE) ranged from 5.1 % to 9.3 %. Four SNP loci from these QTLs were associated with the phenotypic traits validated by Kompetitive Allele Specific PCR or Sanger sequencing. In addition, the expression of three candidate genes for growth traits and five candidate genes for hypoxia tolerance was examined in different growth speed populations and the process of hypoxia exposure and reoxygenation, respectively. The high-density genetic linkage map and QTLs for growth traits and hypoxia tolerance obtained in the present study could further provide the basis for genetic breeding and molecular marker-assisted breeding of Chinese longsnout catfish.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111157"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568304","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}
引用次数: 0
TIMP1: A novel immune-related signature associated with invasiveness and inhibition of pituitary adenoma TIMP1:一种新的与垂体腺瘤侵袭性和抑制相关的免疫相关信号。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-10-17 DOI: 10.1016/j.ygeno.2025.111140
Hongyu Wu , Yu Zhang , Xin Ma , Zenghua Mi , Zhijun Yang
The invasiveness of pituitary adenomas is closely related to the tumour immune microenvironment. This study aimed to identify immune-related genes associated with IPAs. Transcriptomic data from 32 patient-derived samples were analysed to screen immune-related differentially expressed genes between IPAs and non-invasive pituitary adenomas. Weighted gene co-expression network analysis of merged datasets (GSE26966 and GSE51618) was performed to identify hub genes, which were then intersected with immune-related DEGs. Least absolute shrinkage and selection operator regression and support vector machine algorithms consistently identified tissue inhibitor of metalloproteinases 1 (TIMP1) as a key immune-associated invasive gene. Multi-omics validation confirmed significant downregulation of TIMP1 in IPAs. Functional enrichment, single-sample gene set enrichment analysis, CIBERSORT, and immune checkpoint profiling linked TIMP1 to macrophage infiltration and immune regulation. Immunohistochemistry and in vitro experiments further demonstrated that TIMP1 overexpression inhibited tumour-cell proliferation, invasion, and migration. Collectively, these findings suggest that TIMP1 downregulation may promote IPA progression through immune dysregulation.
垂体腺瘤的侵袭性与肿瘤免疫微环境密切相关。本研究旨在鉴定与IPAs相关的免疫相关基因。我们分析了来自32例患者样本的转录组学数据,以筛选IPAs和非侵袭性垂体腺瘤之间的免疫相关差异表达基因。对合并的数据集(GSE26966和GSE51618)进行加权基因共表达网络分析,以确定中心基因,然后将其与免疫相关的deg相交。最小绝对收缩、选择算子回归和支持向量机算法一致确定组织金属蛋白酶抑制剂1 (TIMP1)是一个关键的免疫相关侵袭基因。多组学验证证实了IPAs中TIMP1的显著下调。功能富集、单样本基因集富集分析、CIBERSORT和免疫检查点分析将TIMP1与巨噬细胞浸润和免疫调节联系起来。免疫组织化学和体外实验进一步证实TIMP1过表达抑制肿瘤细胞的增殖、侵袭和迁移。总的来说,这些发现表明TIMP1下调可能通过免疫失调促进IPA的进展。
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引用次数: 0
High-fat diet promotes kidney lipid droplet deposition contributing to the pathogenesis of obesity-related glomerulopathy in mice through gut microbial metabolism 高脂肪饮食通过肠道微生物代谢促进肾脏脂滴沉积,参与小鼠肥胖相关性肾小球病变的发病机制。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-11-03 DOI: 10.1016/j.ygeno.2025.111151
Kai-Wen Cai , Ying-Ying Xie , Zi-Yan Deng , Zong-Chao Yu , Hong-Wei Wu , Zhuang-Feng Weng , Zhen-Chuan Lin , Bin Xia , Xiao-Hua Wang , Zhi-Hua Zheng , Chun Tang , Ting Zhu , Yong-Ping Lu

Background

Obesity-related glomerulopathy (ORG) is a kidney disorder associated with obesity, where dysbiosis of the gut microbiota and disturbances in lipid metabolism play crucial roles in its development. However, the exact mechanisms by which imbalances in gut microbiota influence lipid metabolism and contribute to the pathogenesis of ORG are still not fully understood.

Methods

A high-fat diet (HFD)-induced ORG model was established using 6-week-old male C57BL/6 J mice to investigate the role of gut microbiota and gut-derived metabolites in ORG progression. 16S rRNA sequencing was employed to profile the gut microbiota, while liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied for metabolite analysis in fecal, serum, and kidney samples.

Results

Compared to age-matched normal diet (ND) mice, ORG mice exhibited significant increases in triglycerides (TG), cholesterol (CHO), and urinary albumin-to-creatinine ratio (UACR), alongside enhanced lipid droplet accumulation in renal tubules and glomerular hypertrophy. Metabolomic analysis revealed altered metabolic profiles in ORG mice, particularly the reprogramming of glycerophospholipid metabolism. Additionally, 16S rRNA sequencing demonstrated reduced gut microbiota diversity in ORG mice relative to the ND group. Further investigation revealed that the shift in renal glycerophospholipid metabolism and elevated blood lipid levels in ORG mice were closely linked to gut microbiota dysbiosis, specifically increased abundance of Lachnospiraceae and decreased abundance of Muribaculaceae.

Conclusion

The dysbiosis of gut microbiota induced by a HFD leads to glycerophospholipid metabolic reprogramming, promoting lipid droplet deposition in the kidneys and contributing to ORG progression. Our study highlights the contribution of gut microbial metabolism to the development of ORG, offering new perspectives for potential therapeutic strategies targeting the gut in ORG treatment.
背景:肥胖相关性肾小球病(obesity -related glomerullopathy, ORG)是一种与肥胖相关的肾脏疾病,其中肠道菌群失调和脂质代谢紊乱在其发展中起着至关重要的作用。然而,肠道菌群失衡影响脂质代谢并导致ORG发病的确切机制尚不完全清楚。方法:以6周龄雄性C57BL/6 J小鼠为实验对象,建立高脂饮食(HFD)诱导的ORG模型,研究肠道菌群和肠道源性代谢物在ORG进展中的作用。采用16S rRNA测序分析肠道微生物群,采用液相色谱-串联质谱(LC-MS/MS)分析粪便、血清和肾脏样品的代谢物。结果:与年龄匹配的正常饮食(ND)小鼠相比,ORG小鼠表现出甘油三酯(TG)、胆固醇(CHO)和尿白蛋白与肌酐比率(UACR)的显著增加,同时肾小管脂滴积聚增强,肾小球肥大。代谢组学分析显示,ORG小鼠的代谢谱发生了改变,尤其是甘油磷脂代谢的重编程。此外,16S rRNA测序显示,相对于ND组,ORG小鼠的肠道微生物群多样性减少。进一步的研究表明,ORG小鼠肾脏甘油磷脂代谢的改变和血脂水平的升高与肠道菌群失调密切相关,特别是Lachnospiraceae的丰度增加和Muribaculaceae的丰度减少。结论:HFD诱导的肠道菌群失调导致甘油磷脂代谢重编程,促进肾脏脂滴沉积,促进ORG进展。我们的研究强调了肠道微生物代谢对ORG发展的贡献,为ORG治疗中针对肠道的潜在治疗策略提供了新的视角。
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引用次数: 0
Organelle genomes of progeny of Tripidium arundinaceum × Saccharum spontaneum and sugarcane cultivar revealed their inheritance and characterization after hybridization 杂交后的三叶草(Tripidium arundinaceum × Saccharum spontanum)与甘蔗品种后代细胞器基因组揭示了它们的遗传和特性。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-17 DOI: 10.1016/j.ygeno.2025.111107
Sicheng Li , Shan Zhou , Fengzhen Wu , Yuxin Huang , Yang Zhao , Baoqing Zhang , Gemin Zhang , Weixing Duan , Xiping Yang
Sugarcane (Saccharum spp.) breeding often involves hybridization with distantly related wild species (such as Tripidium arundinaceum) to improve stress resistance, but mitochondrial and chloroplast inheritance across multiple backcross generations remains poorly understood. In this study, we employed PacBio and Illumina sequencing to assemble and compare the mitochondrial genomes (mitogenomes) and chloroplast genome of four genotypes: an distant hybrid F₁ GXAS 07–6-1 (Tripidium arundinaceum × Saccharum spontaneum), a subsequent hybrid F₁ GXASF1 08–2-28, a first-generation backcross GXASBC1 12-A6–3, and a second-generation backcross GXASBC2 15–114. Maternal inheritance preserves key co-linear gene clusters, whereas MTPT content varies, indicating post-hybridization structural adjustments. Our study confirms strict maternal inheritance of mitochondrial and chloroplast genomes across hybrid and backcross generations and validates mitochondrial transmission using organelle-specific markers, providing insights into organellar inheritance and references for sugarcane breeding.
甘蔗(Saccharum spp)的育种通常涉及与远亲野生物种(如Tripidium arundinaceum)杂交以提高抗逆性,但线粒体和叶绿体在多个回交代之间的遗传仍然知之甚少。在本研究中,我们采用PacBio和Illumina测序技术,对远缘杂交品种F₁GXAS 07-6-1 (Tripidium arundinaceum × Saccharum spontanum)、后续杂交品种F₁GXASF1 08-2-28、第一代回交品种GXASBC1 12-A6-3和第二代回交品种GXASBC2 15-114四种基因型的线粒体基因组(有线粒体基因组)和叶绿体基因组进行了组装和比较。母系遗传保留了关键的共线性基因簇,而MTPT含量发生了变化,表明杂交后结构发生了调整。本研究证实了线粒体和叶绿体基因组在杂交代和回交代之间的严格母系遗传,并利用细胞器特异性标记验证了线粒体遗传,为甘蔗细胞器遗传研究提供了新的思路和参考。
{"title":"Organelle genomes of progeny of Tripidium arundinaceum × Saccharum spontaneum and sugarcane cultivar revealed their inheritance and characterization after hybridization","authors":"Sicheng Li ,&nbsp;Shan Zhou ,&nbsp;Fengzhen Wu ,&nbsp;Yuxin Huang ,&nbsp;Yang Zhao ,&nbsp;Baoqing Zhang ,&nbsp;Gemin Zhang ,&nbsp;Weixing Duan ,&nbsp;Xiping Yang","doi":"10.1016/j.ygeno.2025.111107","DOIUrl":"10.1016/j.ygeno.2025.111107","url":null,"abstract":"<div><div>Sugarcane (<em>Saccharum</em> spp.) breeding often involves hybridization with distantly related wild species (such as <em>Tripidium arundinaceum</em>) to improve stress resistance, but mitochondrial and chloroplast inheritance across multiple backcross generations remains poorly understood. In this study, we employed PacBio and Illumina sequencing to assemble and compare the mitochondrial genomes (mitogenomes) and chloroplast genome of four genotypes: an distant hybrid F₁ GXAS 07–6-1 (<em>Tripidium arundinaceum</em> × <em>Saccharum spontaneum</em>), a subsequent hybrid F₁ GXASF<sub>1</sub> 08–2-28, a first-generation backcross GXASBC<sub>1</sub> 12-A6–3, and a second-generation backcross GXASBC<sub>2</sub> 15–114. Maternal inheritance preserves key co-linear gene clusters, whereas MTPT content varies, indicating post-hybridization structural adjustments. Our study confirms strict maternal inheritance of mitochondrial and chloroplast genomes across hybrid and backcross generations and validates mitochondrial transmission using organelle-specific markers, providing insights into organellar inheritance and references for sugarcane breeding.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111107"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091662","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}
引用次数: 0
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Genomics
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