Genomics最新文献_第2页

Construction of an FSH induced liver organoid model for investigating lipid metabolism abnormalities and study of the regulatory role of key lncRNAs FSH诱导肝类器官模型的构建研究脂质代谢异常及关键lncrna的调控作用

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-26 DOI: 10.1016/j.ygeno.2026.111209

Xue Yu, Congcong Shen, Pingping Huang, Bingwen Li, Bailing Zhou, Lijing Wang, Shuoxuan Wang, Yurui Xu, Meng Li, Jie Qu, Guodong Hu, Jihua Wang

Background

The health problems of the elderly, especially the elderly women, are increasingly concerned. The prevalence of abnormal liver lipid metabolism in women after menopause is increasing, which is highly related to estrogen and follicle stimulating hormone. However, hormone replacement therapy is highly controversial, and will bring risks such as breast cancer and coronary heart disease. Therefore, this study aims to build an effective and convenient in vitro disease model and perform functional verification to analyze the molecular mechanism of candidate lncRNAs participating in FSH-induced liver lipid metabolism.

Result

The results indicated the successful preliminary establishment of an in vitro model for FSH-induced lipid metabolism abnormalities. High-throughput sequencing and bioinformatics analysis revealed a total of 174 differentially expressed lncRNAs. Utilizing a comprehensive database, we screened five candidate lncRNAs and conducted interference tests specifically on the upregulated lncRNA ENSMUST00000244884. The findings demonstrated that knocking down this lncRNA led to an increase in the expression of the LXR and ACOX1 genes, which are crucial for lipid metabolism. Consequently, the lipid metabolism abnormality phenotype was alleviated.

Conclusion

Based on the experimental results, we have determined that bile-derived liver organoids are well-suited for constructing an in vitro disease model of hormone-induced lipid metabolism abnormalities, enabling effective observation of lipid phenotypes. Furthermore, we have screened and identified lncRNAs involved in hormone-regulated lipid metabolism abnormalities at the non-coding regulatory level. These findings offer potential diagnostic markers and therapeutic targets for disorders related to lipid metabolism.

老年人，特别是老年妇女的健康问题日益受到关注。绝经后女性肝脏脂质代谢异常的发生率越来越高，这与雌激素和促卵泡激素密切相关。然而，激素替代疗法备受争议，并会带来乳腺癌和冠心病等风险。因此，本研究旨在建立有效便捷的体外疾病模型并进行功能验证，分析候选lncrna参与fsh诱导的肝脏脂质代谢的分子机制。结果fsh诱导的脂质代谢异常体外模型初步建立成功。高通量测序和生物信息学分析共发现174个差异表达的lncrna。利用一个全面的数据库，我们筛选了5个候选lncRNA，并对上调的lncRNA ENSMUST00000244884进行了干扰测试。研究结果表明，敲除该lncRNA导致LXR和ACOX1基因的表达增加，这两个基因对脂质代谢至关重要。从而减轻脂质代谢异常表型。结论基于实验结果，我们确定胆汁来源的肝类器官非常适合构建激素诱导的脂质代谢异常的体外疾病模型，可以有效地观察脂质表型。此外，我们在非编码调控水平上筛选并鉴定了参与激素调节脂质代谢异常的lncrna。这些发现为脂质代谢相关疾病提供了潜在的诊断标记和治疗靶点。

{"title":"Construction of an FSH induced liver organoid model for investigating lipid metabolism abnormalities and study of the regulatory role of key lncRNAs","authors":"Xue Yu, Congcong Shen, Pingping Huang, Bingwen Li, Bailing Zhou, Lijing Wang, Shuoxuan Wang, Yurui Xu, Meng Li, Jie Qu, Guodong Hu, Jihua Wang","doi":"10.1016/j.ygeno.2026.111209","DOIUrl":"10.1016/j.ygeno.2026.111209","url":null,"abstract":"<div><h3>Background</h3><div>The health problems of the elderly, especially the elderly women, are increasingly concerned. The prevalence of abnormal liver lipid metabolism in women after menopause is increasing, which is highly related to estrogen and follicle stimulating hormone. However, hormone replacement therapy is highly controversial, and will bring risks such as breast cancer and coronary heart disease. Therefore, this study aims to build an effective and convenient in vitro disease model and perform functional verification to analyze the molecular mechanism of candidate lncRNAs participating in FSH-induced liver lipid metabolism.</div></div><div><h3>Result</h3><div>The results indicated the successful preliminary establishment of an in vitro model for FSH-induced lipid metabolism abnormalities. High-throughput sequencing and bioinformatics analysis revealed a total of 174 differentially expressed lncRNAs. Utilizing a comprehensive database, we screened five candidate lncRNAs and conducted interference tests specifically on the upregulated lncRNA ENSMUST00000244884. The findings demonstrated that knocking down this lncRNA led to an increase in the expression of the LXR and ACOX1 genes, which are crucial for lipid metabolism. Consequently, the lipid metabolism abnormality phenotype was alleviated.</div></div><div><h3>Conclusion</h3><div>Based on the experimental results, we have determined that bile-derived liver organoids are well-suited for constructing an in vitro disease model of hormone-induced lipid metabolism abnormalities, enabling effective observation of lipid phenotypes. Furthermore, we have screened and identified lncRNAs involved in hormone-regulated lipid metabolism abnormalities at the non-coding regulatory level. These findings offer potential diagnostic markers and therapeutic targets for disorders related to lipid metabolism.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111209"},"PeriodicalIF":3.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074491","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

Human-mediated dispersal and breeding reshape global genomic patterns in black soldier flies 人类介导的扩散和繁殖重塑了黑兵蝇的全球基因组模式。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-25 DOI: 10.1016/j.ygeno.2026.111208

Peter Muchina , Johnson Kinyua , Fathiya Khamis , Chrysantus M. Tanga , Rawlynce Bett , Geoffrey Ssepuuya , Dorothy Nakimbugwe , Mikkel-Holger S. Sinding , Grum Gebreyesus , Goutam Sahana , Zexi Cai

Human activities, either intentional or unintentional, have significantly influenced the global distribution and genetic composition of many species. The black soldier fly (Hermetia illucens; BSF) is a species native to North America that has rapidly gained commercial importance due to its bioconversion efficiency, upcycling organic waste into higher-value products. Through human-mediated dispersal associated with trade and insect farming, BSF has been introduced widely across the Old World, including Africa, where both wild and captive populations are now established. Despite its expanding global distribution, the demographic history and genomic consequences of these introductions remain poorly understood, particularly in Africa. This work integrates whole-genome sequencing of newly sampled East African wild and captive populations with publicly available global datasets to characterize patterns of genetic diversity, population structure, and historical spread. Wild populations displayed high genetic diversity and clear geographic structuring, whereas many captive populations showed markedly reduced diversity, elevated inbreeding, and extensive runs of homozygosity. Our results reveal that a substantial fraction of global captive lines can be traced to a narrow lineage of North American origin, while additional captive colonies reflect more recent, independent derivations from local wild populations. These genomic patterns are consistent with demographic processes such as founder effects, genetic drift, and small effective population sizes, rather than coordinated or directional domestication. By resolving the origins and demographic trajectories of African and global BSF populations, this work clarifies the genetic consequences of unstructured breeding and provides a foundation for managing genetic resources in this rapidly expanding insect-farming industry.

人类活动有意或无意地对许多物种的全球分布和遗传组成产生了重大影响。黑兵蝇（Hermetia illucens； BSF）是一种原产于北美的物种，由于其生物转化效率，将有机废物升级为更高价值的产品，迅速获得了商业重要性。通过与贸易和昆虫养殖相关的人类媒介传播，BSF已在包括非洲在内的旧大陆广泛传播，目前已在那里建立了野生种群和圈养种群。尽管其在全球分布不断扩大，但这些引进的人口历史和基因组后果仍然知之甚少，特别是在非洲。这项工作将新采样的东非野生和圈养种群的全基因组测序与公开可用的全球数据集相结合，以表征遗传多样性、种群结构和历史传播模式。野生种群表现出较高的遗传多样性和明确的地理结构，而许多圈养种群表现出明显的多样性降低、近交增加和广泛的纯合性。我们的研究结果表明，全球圈养系的很大一部分可以追溯到北美起源的狭窄谱系，而额外的圈养殖民地反映了更近的，来自当地野生种群的独立衍生。这些基因组模式与人口统计学过程一致，如奠基人效应、遗传漂变和小的有效种群规模，而不是协调或定向驯化。通过解决非洲和全球BSF种群的起源和人口统计轨迹，这项工作澄清了非结构化育种的遗传后果，并为在这个快速发展的昆虫养殖业中管理遗传资源提供了基础。

{"title":"Human-mediated dispersal and breeding reshape global genomic patterns in black soldier flies","authors":"Peter Muchina , Johnson Kinyua , Fathiya Khamis , Chrysantus M. Tanga , Rawlynce Bett , Geoffrey Ssepuuya , Dorothy Nakimbugwe , Mikkel-Holger S. Sinding , Grum Gebreyesus , Goutam Sahana , Zexi Cai","doi":"10.1016/j.ygeno.2026.111208","DOIUrl":"10.1016/j.ygeno.2026.111208","url":null,"abstract":"<div><div>Human activities, either intentional or unintentional, have significantly influenced the global distribution and genetic composition of many species. The black soldier fly (<em>Hermetia illucens</em>; BSF) is a species native to North America that has rapidly gained commercial importance due to its bioconversion efficiency, upcycling organic waste into higher-value products. Through human-mediated dispersal associated with trade and insect farming, BSF has been introduced widely across the Old World, including Africa, where both wild and captive populations are now established. Despite its expanding global distribution, the demographic history and genomic consequences of these introductions remain poorly understood, particularly in Africa. This work integrates whole-genome sequencing of newly sampled East African wild and captive populations with publicly available global datasets to characterize patterns of genetic diversity, population structure, and historical spread. Wild populations displayed high genetic diversity and clear geographic structuring, whereas many captive populations showed markedly reduced diversity, elevated inbreeding, and extensive runs of homozygosity. Our results reveal that a substantial fraction of global captive lines can be traced to a narrow lineage of North American origin, while additional captive colonies reflect more recent, independent derivations from local wild populations. These genomic patterns are consistent with demographic processes such as founder effects, genetic drift, and small effective population sizes, rather than coordinated or directional domestication. By resolving the origins and demographic trajectories of African and global BSF populations, this work clarifies the genetic consequences of unstructured breeding and provides a foundation for managing genetic resources in this rapidly expanding insect-farming industry.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111208"},"PeriodicalIF":3.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146061792","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

Integrated multi-omics analysis reveals gamma-aminobutyric acid as a key regulator of social genetic effects on residual feed intake in pigs 综合多组学分析显示-氨基丁酸是社会遗传效应对猪剩余采食量的关键调节因子。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-22 DOI: 10.1016/j.ygeno.2026.111207

Patrick Kofi Makafui Tecku , Zhenjian Zhao , Dong Chen , Shengdi Cui , Junge Wang , Shixin Yu , Ziyang Chen , Yaoxi Zhou , Runjie Huang , Wenxuan Zhou , Jia Xue , Guoqing Tang

Residual feed intake (RFI) is an important indicator of feed efficiency influenced by social interactions. However, the molecular mechanisms underlying social genetic effects on RFI (RFI-SGE) remain unclear. This study employed multi-omics analysis to investigate RFI-SGE in pigs, analyzing liver, ileum, and cecum tissues from high and low RFI-SGE groups. Transcriptomic and proteomic analyses revealed significant differences in gene and protein expressions, with liver pathways enriched in oxidative phosphorylation and ileum pathways linked to amino acid metabolism. Metabolomic analysis identified gamma-aminobutyric acid (GABA) as consistently upregulated in high RFI-SGE pigs. Integrated analysis revealed strong associations between GABA and its biosynthetic genes and upstream precursors (MAOB, DAO, ASS1, and OAT). Enhanced GABA signaling may improve social adaptability, metabolic regulation, and feed efficiency in pigs. The identification of GABA as a potential key regulator of RFI-SGE provides valuable insights for improving feed efficiency and animal welfare through targeted breeding strategies.

剩余采食量（RFI）是受社会交往影响的饲料效率的重要指标。然而，社会遗传影响RFI的分子机制（RFI- sge）仍不清楚。本研究采用多组学分析方法研究猪的RFI-SGE，分析了RFI-SGE高组和低组的肝脏、回肠和盲肠组织。转录组学和蛋白质组学分析揭示了基因和蛋白质表达的显著差异，肝脏途径富含氧化磷酸化，回肠途径与氨基酸代谢有关。代谢组学分析发现γ -氨基丁酸（GABA）在高RFI-SGE猪中持续上调。综合分析显示，GABA及其生物合成基因与上游前体（MAOB、DAO、ASS1和OAT）之间存在很强的相关性。GABA信号的增强可能提高猪的社会适应性、代谢调节和饲料效率。确定GABA是RFI-SGE的潜在关键调控因子，为通过有针对性的育种策略提高饲料效率和动物福利提供了有价值的见解。

{"title":"Integrated multi-omics analysis reveals gamma-aminobutyric acid as a key regulator of social genetic effects on residual feed intake in pigs","authors":"Patrick Kofi Makafui Tecku , Zhenjian Zhao , Dong Chen , Shengdi Cui , Junge Wang , Shixin Yu , Ziyang Chen , Yaoxi Zhou , Runjie Huang , Wenxuan Zhou , Jia Xue , Guoqing Tang","doi":"10.1016/j.ygeno.2026.111207","DOIUrl":"10.1016/j.ygeno.2026.111207","url":null,"abstract":"<div><div>Residual feed intake (RFI) is an important indicator of feed efficiency influenced by social interactions. However, the molecular mechanisms underlying social genetic effects on RFI (RFI-SGE) remain unclear. This study employed multi-omics analysis to investigate RFI-SGE in pigs, analyzing liver, ileum, and cecum tissues from high and low RFI-SGE groups. Transcriptomic and proteomic analyses revealed significant differences in gene and protein expressions, with liver pathways enriched in oxidative phosphorylation and ileum pathways linked to amino acid metabolism. Metabolomic analysis identified gamma-aminobutyric acid (GABA) as consistently upregulated in high RFI-SGE pigs. Integrated analysis revealed strong associations between GABA and its biosynthetic genes and upstream precursors (<em>MAOB</em>, <em>DAO</em>, <em>ASS1</em>, and <em>OAT</em>). Enhanced GABA signaling may improve social adaptability, metabolic regulation, and feed efficiency in pigs. The identification of GABA as a potential key regulator of RFI-SGE provides valuable insights for improving feed efficiency and animal welfare through targeted breeding strategies.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111207"},"PeriodicalIF":3.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044015","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

A haplotype reference panel and genotype imputation framework for the black soldier fly (Hermetia illucens) 黑兵蝇（Hermetia illucens）的单倍型参考面板和基因型插入框架。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-20 DOI: 10.1016/j.ygeno.2026.111206

Peter Muchina , Johnson Kinyua , Fathiya Khamis , Chrysantus M. Tanga , Maria Altaf Satti , Grum Gebreyesus , Goutam Sahana , Zexi Cai

Low-coverage whole genome sequencing (lcWGS) combined with genotype imputation provides a cost-efficient alternative to high-coverage sequencing for large-scale genotyping. Although widely implemented in human and livestock genomics, this strategy has not yet been systematically optimized for insects of industrial importance. The black soldier fly (BSF, Hermetia illucens) is increasingly used in global waste bioconversion and sustainable protein production, but genomic resources remain limited. Here, we develop the first BSF haplotype reference panel, containing ∼29.8 million high-quality SNPs from 168 high-coverage genomes, and benchmark imputation performance using a validation experiment in which 33 high-coverage individuals were down-sampled to low coverage and imputed against a reference panel of 135 individuals. We evaluated the performance of three imputation tools, QUILT v1.0.5, GLIMPSE2, and STITCH v1.7.2, across multiple sequencing depths (0.5 × −3×) and allele frequency bins. Based on this validation, QUILT v1.0.5 achieved the highest accuracy overall, particularly for rare variants (MAF < 0.05), whereas GLIMPSE2 delivered comparable accuracy for common variants with approximately twofold faster runtimes. STITCH enabled reference-free imputation but exhibited reduced accuracy relative to reference-based approaches. We then applied the optimized framework to 180 low-coverage (∼1×) BSF genomes, demonstrating the practical utility of the reference panel for large-scale genotyping when true genotypes are unavailable. Together, the reference panel, benchmarking results, and accompanying lcWGS pipeline establish a validated framework for cost-effective BSF genotyping, enabling downstream applications in population monitoring, diversity assessment, and selective breeding.

低覆盖率全基因组测序（lcWGS）结合基因型插入为大规模基因分型的高覆盖率测序提供了一种经济有效的替代方法。尽管这一策略在人类和牲畜基因组学中得到了广泛应用，但尚未对具有工业重要性的昆虫进行系统优化。黑兵蝇（Hermetia illucens）越来越多地用于全球废物生物转化和可持续蛋白质生产，但基因组资源仍然有限。在这里，我们开发了第一个BSF单倍型参考面板，包含来自168个高覆盖基因组的约2980万个高质量snp，并使用验证实验对基准插补性能进行了验证，其中33个高覆盖个体降采样到低覆盖个体，并与135个个体的参考面板进行了插补。我们在多个测序深度（0.5 × - 3x）和等位基因频率箱中评估了三种插入工具，QUILT v1.0.5， GLIMPSE2和STITCH v1.7.2的性能。基于此验证，QUILT v1.0.5总体上达到了最高的准确性，特别是对于罕见的变体（MAF）

{"title":"A haplotype reference panel and genotype imputation framework for the black soldier fly (Hermetia illucens)","authors":"Peter Muchina , Johnson Kinyua , Fathiya Khamis , Chrysantus M. Tanga , Maria Altaf Satti , Grum Gebreyesus , Goutam Sahana , Zexi Cai","doi":"10.1016/j.ygeno.2026.111206","DOIUrl":"10.1016/j.ygeno.2026.111206","url":null,"abstract":"<div><div>Low-coverage whole genome sequencing (lcWGS) combined with genotype imputation provides a cost-efficient alternative to high-coverage sequencing for large-scale genotyping. Although widely implemented in human and livestock genomics, this strategy has not yet been systematically optimized for insects of industrial importance. The black soldier fly (BSF, <em>Hermetia illucens</em>) is increasingly used in global waste bioconversion and sustainable protein production, but genomic resources remain limited. Here, we develop the first BSF haplotype reference panel, containing ∼29.8 million high-quality SNPs from 168 high-coverage genomes, and benchmark imputation performance using a validation experiment in which 33 high-coverage individuals were down-sampled to low coverage and imputed against a reference panel of 135 individuals. We evaluated the performance of three imputation tools, QUILT v1.0.5, GLIMPSE2, and STITCH v1.7.2, across multiple sequencing depths (0.5 × −3×) and allele frequency bins. Based on this validation, QUILT v1.0.5 achieved the highest accuracy overall, particularly for rare variants (MAF < 0.05), whereas GLIMPSE2 delivered comparable accuracy for common variants with approximately twofold faster runtimes. STITCH enabled reference-free imputation but exhibited reduced accuracy relative to reference-based approaches. We then applied the optimized framework to 180 low-coverage (∼1×) BSF genomes, demonstrating the practical utility of the reference panel for large-scale genotyping when true genotypes are unavailable. Together, the reference panel, benchmarking results, and accompanying lcWGS pipeline establish a validated framework for cost-effective BSF genotyping, enabling downstream applications in population monitoring, diversity assessment, and selective breeding.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111206"},"PeriodicalIF":3.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018040","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

Dbert2_LR: A deep learning-based model for predicting cis-regulatory elements in crops 基于深度学习的作物顺式调控因子预测模型。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-14 DOI: 10.1016/j.ygeno.2026.111201

Huan Liu , Faxu Guo , Longyu Huang , Jian Wang , Guomin Zhou , Jianhua Zhang

Cis-regulatory elements (CREs) are key determinants of gene expression underlying complex agronomic traits. However, accurately identifying CREs in crops with large and highly repetitive genomes (such as upland cotton) remains extremely challenging. To address this, we developed Dbert2_LR, a novel hybrid deep-learning framework that integrates the pretrained genomic foundation model DNABERT-2 with parallel bidirectional RNN and LSTM networks. This architecture efficiently captures both deep contextual dependencies and local sequence patterns in DNA, enabling high-accuracy classification of promoters, enhancers, and non-regulatory sequences. Systematic evaluations on Arabidopsis thaliana and upland cotton show that Dbert2_LR outperforms multiple benchmark models, achieving macro-averaged F1 scores of 0.890 and 0.637, respectively. More importantly, in-silico saturation mutagenesis (ISM) analysis confirmed that the model's decisions strongly depend on known transcription factor binding motifs such as TATA-box, DOF, and E-box, revealing its biological interpretability and helping overcome the “black-box” nature of deep learning. To facilitate broader use, we also developed user-friendly A_cre and C_cre prediction systems. This study provides a powerful new tool for functional annotation of complex crop genomes and lays the foundation for CRE-based molecular breeding design.

顺式调控元件（cre）是复杂农艺性状基因表达的关键决定因素。然而，准确识别具有大量和高度重复基因组的作物（如陆地棉花）的cre仍然极具挑战性。为了解决这个问题，我们开发了一种新的混合深度学习框架，将预训练的基因组基础模型DNABERT-2与并行双向RNN和LSTM网络集成在一起。该体系结构有效地捕获DNA中的深层上下文依赖关系和局部序列模式，从而实现启动子、增强子和非调控序列的高精度分类。对拟南芥和陆地棉的系统评价表明，Dbert2_LR优于多个基准模型，宏观平均F1得分分别为0.890和0.637。更重要的是，硅饱和诱变（ISM）分析证实，该模型的决策强烈依赖于已知的转录因子结合基元，如TATA-box、DOF和E-box，揭示了其生物学可解释性，并有助于克服深度学习的“黑盒子”性质。为了方便更广泛的使用，我们还开发了用户友好的A_cre和C_cre预测系统。该研究为复杂作物基因组的功能标注提供了强有力的新工具，并为基于cre的分子育种设计奠定了基础。

{"title":"Dbert2_LR: A deep learning-based model for predicting cis-regulatory elements in crops","authors":"Huan Liu , Faxu Guo , Longyu Huang , Jian Wang , Guomin Zhou , Jianhua Zhang","doi":"10.1016/j.ygeno.2026.111201","DOIUrl":"10.1016/j.ygeno.2026.111201","url":null,"abstract":"<div><div>Cis-regulatory elements (CREs) are key determinants of gene expression underlying complex agronomic traits. However, accurately identifying CREs in crops with large and highly repetitive genomes (such as upland cotton) remains extremely challenging. To address this, we developed Dbert2_LR, a novel hybrid deep-learning framework that integrates the pretrained genomic foundation model DNABERT-2 with parallel bidirectional RNN and LSTM networks. This architecture efficiently captures both deep contextual dependencies and local sequence patterns in DNA, enabling high-accuracy classification of promoters, enhancers, and non-regulatory sequences. Systematic evaluations on Arabidopsis <em>thaliana</em> and upland cotton show that Dbert2_LR outperforms multiple benchmark models, achieving macro-averaged F1 scores of 0.890 and 0.637, respectively. More importantly, in-silico saturation mutagenesis (ISM) analysis confirmed that the model's decisions strongly depend on known transcription factor binding motifs such as TATA-box, DOF, and E-box, revealing its biological interpretability and helping overcome the “black-box” nature of deep learning. To facilitate broader use, we also developed user-friendly A_cre and C_cre prediction systems. This study provides a powerful new tool for functional annotation of complex crop genomes and lays the foundation for CRE-based molecular breeding design.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111201"},"PeriodicalIF":3.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988944","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

Dynamic changes in rumen fermentation, microbial communities, and metabolite profiles of non-pregnant and gestational Ashidan yaks 非妊娠和妊娠阿西丹牦牛瘤胃发酵、微生物菌群及其代谢产物相互作用模式的比较。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-14 DOI: 10.1016/j.ygeno.2026.111205

Xuhui Liu , Junxia Zhang , Yanmei Niu , Yanbin Bai , Xue Jia , Siyi Cai , Yicheng Wang , Xiaolan Zhang , Bingang Shi , Jiang Hu , Chengfu Zhang , Zhidong Zhao

Rumen microbiota and their metabolites in ruminants across reproductive stages benefit the animals' growth, health and offspring's development. However, the impact of rumen fermentation profiles, microbial composition, and metabolite dynamics between non-pregnant and gestating Ashidan yaks remains poorly understood. This study analyzed the rumen fermentation, metagenome and metabolome of five 2–3-year-old Ashidan yaks during the non-pregnant period (NP; 11–30 days pre-mating) and the gestational period (GP; 112–148 days post-conception). Research has found that gestation had higher acetic acid and ammonia nitrogen (NH₃−N) (P < 0.05), increased Ascomycota, Apicomplexa, Rhodococcus, Acinetobacter, Methanosphaera (P < 0.05); differential metabolites enriched in valine, leucine, isoleucine biosynthesis and histidine metabolism (P < 0.05), with L-threonine and urocanic acid as major ones. Additionally, microorganisms, metabolites and fermentation parameters correlated. The study shows Ashidan yaks adapt to reproductive stages via regulating rumen microbiota and metabolism, providing a basis for feeding management.

反刍动物生殖各阶段瘤胃微生物群及其代谢产物对动物的生长、健康和后代的发育都有重要影响。然而，对非妊娠期和妊娠期阿西丹牦牛瘤胃发酵特征、微生物组成和代谢物动力学的影响尚不清楚。本研究分析了5头2-3岁阿西丹牦牛非妊娠期（NP；孕前11-30 d）和妊娠期（GP；受孕后112-148 d）的瘤胃发酵、宏基因组和代谢组。研究发现，妊娠期醋酸和氨氮（NH3-N） (P

{"title":"Dynamic changes in rumen fermentation, microbial communities, and metabolite profiles of non-pregnant and gestational Ashidan yaks","authors":"Xuhui Liu , Junxia Zhang , Yanmei Niu , Yanbin Bai , Xue Jia , Siyi Cai , Yicheng Wang , Xiaolan Zhang , Bingang Shi , Jiang Hu , Chengfu Zhang , Zhidong Zhao","doi":"10.1016/j.ygeno.2026.111205","DOIUrl":"10.1016/j.ygeno.2026.111205","url":null,"abstract":"<div><div>Rumen microbiota and their metabolites in ruminants across reproductive stages benefit the animals' growth, health and offspring's development. However, the impact of rumen fermentation profiles, microbial composition, and metabolite dynamics between non-pregnant and gestating Ashidan yaks remains poorly understood. This study analyzed the rumen fermentation, metagenome and metabolome of five 2–3-year-old Ashidan yaks during the non-pregnant period (NP; 11–30 days pre-mating) and the gestational period (GP; 112–148 days post-conception). Research has found that gestation had higher acetic acid and ammonia nitrogen (NH<sub>3</sub>−N) (<em>P</em> < 0.05), increased Ascomycota, Apicomplexa, <em>Rhodococcus</em>, <em>Acinetobacter</em>, <em>Methanosphaera</em> (<em>P</em> < 0.05); differential metabolites enriched in valine, leucine, isoleucine biosynthesis and histidine metabolism (<em>P</em> < 0.05), with L-threonine and urocanic acid as major ones. Additionally, microorganisms, metabolites and fermentation parameters correlated. The study shows Ashidan yaks adapt to reproductive stages via regulating rumen microbiota and metabolism, providing a basis for feeding management.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111205"},"PeriodicalIF":3.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988936","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

Characteristics of microbial community succession and functional metabolite accumulation during microaerobic fermentation of high-sugar-load fruit and vegetable residues: Potential implications for guiding home production of environmental-friendly bioactive fertilizer 高糖果蔬残渣微氧发酵过程中微生物群落演替和功能代谢物积累特征：对指导家庭生产环保型生物活性肥料的潜在意义

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-13 DOI: 10.1016/j.ygeno.2026.111204

Piao Liu , Guandi He , Zicheng Guo , Yu Tang , Zhengqian Tan , Yulin Song , Tengbing He , Siew Ling Lee

Household fermentation tanks offer simple, low-cost solutions for fruit and vegetable waste utilization, yet staged metabolite formation during sugar-mediated fermentation remains understudied. Using metagenomic and metabolomic approaches, we characterized microbial succession and metabolite dynamics over 28 days. Three phases emerged: substrate activation (1-7d) with Enterobacter/Escherichia dominance producing organic acids; metabolic transition (8-21d) with Lactiplantibacillus proliferation (312.5% increase) accumulating phytohormones 3-hydroxycinnamic acid (2.84-fold) and adenine (1.38-fold); functional stability (21-28d) establishing Lactiplantibacillus-Acetobacter synergy enriching antioxidants and antimicrobial peptides. Multi-omics analysis revealed strong correlations between amino acid metabolism and functional metabolites (r = 0.78, p < 0.01). Fermentation broth (1:500 dilution) enhanced lettuce germination to 92.22% (p < 0.05).Although the potential of household agriculture is demonstrated through staged microbial community development and the formation of bioactive products, functional characteristics still need to be verified in the soil-plant system beyond seed germination assays.

家用发酵罐为果蔬废弃物的利用提供了简单、低成本的解决方案，但糖介导的发酵过程中代谢物的分期形成仍有待研究。利用宏基因组学和代谢组学方法，我们对28天内的微生物演替和代谢物动态进行了表征。出现了三个阶段：底物激活（1-7d），肠杆菌/埃希氏菌优势产生有机酸；代谢转变（8-21d）与乳酸杆菌增殖（增加312.5%）积累植物激素3-羟基肉桂酸（2.84倍）和腺嘌呤（1.38倍）；功能稳定（21-28d）建立乳酸杆菌-醋酸杆菌协同作用，丰富抗氧化剂和抗菌肽。多组学分析显示，氨基酸代谢与功能代谢物之间存在很强的相关性（r = 0.78, p < 0.01）。发酵液（1:500稀释）使生菜发芽率提高到92.22% （p < 0.05）。虽然家庭农业的潜力是通过分阶段的微生物群落发展和生物活性产品的形成来证明的，但除了种子发芽试验之外，还需要在土壤-植物系统中验证功能特征。

{"title":"Characteristics of microbial community succession and functional metabolite accumulation during microaerobic fermentation of high-sugar-load fruit and vegetable residues: Potential implications for guiding home production of environmental-friendly bioactive fertilizer","authors":"Piao Liu , Guandi He , Zicheng Guo , Yu Tang , Zhengqian Tan , Yulin Song , Tengbing He , Siew Ling Lee","doi":"10.1016/j.ygeno.2026.111204","DOIUrl":"10.1016/j.ygeno.2026.111204","url":null,"abstract":"<div><div>Household fermentation tanks offer simple, low-cost solutions for fruit and vegetable waste utilization, yet staged metabolite formation during sugar-mediated fermentation remains understudied. Using metagenomic and metabolomic approaches, we characterized microbial succession and metabolite dynamics over 28 days. Three phases emerged: substrate activation (1-7d) with <em>Enterobacter</em>/<em>Escherichia</em> dominance producing organic acids; metabolic transition (8-21d) with <em>Lactiplantibacillus</em> proliferation (312.5% increase) accumulating phytohormones 3-hydroxycinnamic acid (2.84-fold) and adenine (1.38-fold); functional stability (21-28d) establishing <em>Lactiplantibacillus-Acetobacter</em> synergy enriching antioxidants and antimicrobial peptides. Multi-omics analysis revealed strong correlations between amino acid metabolism and functional metabolites (<em>r</em> = 0.78, <em>p</em> < 0.01). Fermentation broth (1:500 dilution) enhanced lettuce germination to 92.22% (<em>p</em> < 0.05).Although the potential of household agriculture is demonstrated through staged microbial community development and the formation of bioactive products, functional characteristics still need to be verified in the soil-plant system beyond seed germination assays.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111204"},"PeriodicalIF":3.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975340","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

Dynamics of deleterious mutation and selection at seven nuclear genes during barley domestication and de-domestication 大麦驯化和去驯化过程中7个核基因的有害突变和选择动态。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-11 DOI: 10.1016/j.ygeno.2026.111203

Yu Zhou , Yuxi Tong , Yonggang Wang , Xiaoqin Fu , Chen Zhang , Genlou Sun , Qifei Wang , Sisi Huang , Xifeng Ren

Understanding how barley domestication affects deleterious mutations is crucial for breeding and germplasm conservation. This study analyzed seven single-copy nuclear genes (Alcohol dehydrogenase 2 (ADH2), Alcohol dehydrogenase 3 (ADH3), Dehydrin9 (DHN9), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Phosphoenolpyruvate carboxylase (PEPC), Photoperiod response gene (PPD-H1), and Granule-bound starch synthase (WAXY)) in 179 wild, 185 domesticated, and 21 de-domesticated barley accessions. Results showed that wild barley has the highest genetic diversity and the most private haplotypes. Deleterious SNPs were identified, with fewer in domesticated and de-domesticated groups compared to wild. Deleterious mutation load decreased from wild to domesticated barley as nucleotide diversity decreased (R = 0.78; p < 0.05), suggesting that domestication bottlenecks may purge these mutations. In wild barley, Nonsynonymous-to-synonymous substitution rate (dN/dS) ratios were ∼ 1 or > 1, indicating neutral or weak positive selection. These findings highlight how domestication shapes deleterious mutation patterns and provide insights for breeding and germplasm management.

了解大麦驯化如何影响有害突变对育种和种质资源保护至关重要。本研究分析了179份野生、185份驯化和21份去驯化大麦材料的7个单拷贝核基因（酒精脱氢酶2 （ADH2）、酒精脱氢酶3 （ADH3）、脱氢酶9 （DHN9）、甘油醛-3-磷酸脱氢酶（GAPDH）、磷酸烯醇丙酮酸羧化酶（PEPC）、光周期反应基因（PPD-H1）和颗粒结合淀粉合成酶（WAXY））。结果表明，野生大麦具有最高的遗传多样性和最多的私有单倍型。在驯化和去驯化群体中，与野生群体相比，有害的snp较少。随着核苷酸多样性的降低，从野生大麦到驯化大麦的有害突变负荷降低（R = 0.78;p  1），表明中性或弱正向选择。这些发现突出了驯化如何形成有害的突变模式，并为育种和种质资源管理提供了见解。

{"title":"Dynamics of deleterious mutation and selection at seven nuclear genes during barley domestication and de-domestication","authors":"Yu Zhou , Yuxi Tong , Yonggang Wang , Xiaoqin Fu , Chen Zhang , Genlou Sun , Qifei Wang , Sisi Huang , Xifeng Ren","doi":"10.1016/j.ygeno.2026.111203","DOIUrl":"10.1016/j.ygeno.2026.111203","url":null,"abstract":"<div><div>Understanding how barley domestication affects deleterious mutations is crucial for breeding and germplasm conservation. This study analyzed seven single-copy nuclear genes (<em>Alcohol dehydrogenase 2</em> (<em>ADH2</em>), <em>Alcohol dehydrogenase 3</em> (<em>ADH3</em>), <em>Dehydrin9</em> (<em>DHN9</em>), <em>Glyceraldehyde-3-phosphate dehydrogenase</em> (<em>GAPDH</em>), <em>Phosphoenolpyruvate carboxylase</em> (<em>PEPC</em>), <em>Photoperiod response gene</em> (<em>PPD-H1</em>), and <em>Granule-bound starch synthase</em> (<em>WAXY</em>)) in 179 wild, 185 domesticated, and 21 de-domesticated barley accessions. Results showed that wild barley has the highest genetic diversity and the most private haplotypes. Deleterious SNPs were identified, with fewer in domesticated and de-domesticated groups compared to wild. Deleterious mutation load decreased from wild to domesticated barley as nucleotide diversity decreased (<em>R</em> = 0.78; <em>p</em> < 0.05), suggesting that domestication bottlenecks may purge these mutations. In wild barley, Nonsynonymous-to-synonymous substitution rate (dN/dS) ratios were ∼ 1 or > 1, indicating neutral or weak positive selection. These findings highlight how domestication shapes deleterious mutation patterns and provide insights for breeding and germplasm management.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111203"},"PeriodicalIF":3.0,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965882","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

Microbial community differences between healthy and Ustilago-infected oats 健康燕麦与黑穗病菌感染燕麦的微生物群落差异

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-10 DOI: 10.1016/j.ygeno.2026.111202

Chao Cheng , Songhe Xu , Zhiguo Liu , Hui Zhang , Yuening Yang , Yiheng Zhang , Ermeng Ge , Jiaming Xu , Qingze Zhu , Xinru Li , Bo Yu , Mengqi Liu , Yan Guo

Ustilago, a pathogenic fungus, poses a serious threat to oat growth and yield. However, the species composition, abundance, and distribution of microbial communities in Ustilago-infected oats remain poorly characterized. In this study, we conducted 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing and biochemical assays to compare microbial profiles and physiological traits between healthy (n = 60) and Ustilago-infected oats (n = 60). Our analyses revealed higher bacterial diversity in healthy oats, particularly in the spikes and stems. Significant shifts in microbial community structure were observed across all tissues in diseased plants. While the microbiome of healthy oats predominantly comprised beneficial bacteria, including Exiguobacterium indicum, infected plants were largely colonized by pathogens, including Ustilago hordei, Pyrenophora chaetomioides, and Curtobacterium flaccumfaciens pv. flaccumfaciens, suggesting the occurrence of disease-driven microbial restructuring. Functional predictions indicated that enriched pathways were primarily associated with metabolism, followed by genetic information processing and environmental signal transduction. Malondialdehyde content was significantly lower in most healthy oat tissues compared to Ustilago-infected oats, whereas the activities of the antioxidant enzymes superoxide dismutase and peroxidase were markedly higher. These results implied that Ustilago infection induced severe oxidative damage to membrane systems, likely compromising the plant's ability to scavenge superoxide ions and hydrogen peroxide, thereby reducing overall plant health.

黑穗病菌是一种严重威胁燕麦生长和产量的病原菌。然而，在黑穗病感染的燕麦中，微生物群落的种类组成、丰度和分布特征仍然很差。在这项研究中，我们通过16S rRNA和ITS扩增子测序和生化分析来比较健康燕麦（n = 60）和ustilago感染燕麦（n = 60）的微生物特征和生理性状。我们的分析显示，健康燕麦的细菌多样性更高，尤其是在穗和茎中。在患病植物的所有组织中都观察到微生物群落结构的显著变化。虽然健康燕麦的微生物组主要由有益细菌组成，包括肠外革杆菌，但受感染的植物主要由病原体定殖，包括黑穗病菌、毛状芽孢杆菌和flaccumfaciens pv。flacfaciens，提示发生了疾病驱动的微生物重组。功能预测表明，富集的通路主要与代谢相关，其次是遗传信息处理和环境信号转导。与黑穗病菌感染的燕麦相比，大多数健康燕麦组织中丙二醛含量显著降低，而抗氧化酶超氧化物歧化酶和过氧化物酶活性显著升高。这些结果表明，黑穗病菌感染对膜系统造成了严重的氧化损伤，可能损害了植物清除超氧离子和过氧化氢的能力，从而降低了植物的整体健康。

{"title":"Microbial community differences between healthy and Ustilago-infected oats","authors":"Chao Cheng , Songhe Xu , Zhiguo Liu , Hui Zhang , Yuening Yang , Yiheng Zhang , Ermeng Ge , Jiaming Xu , Qingze Zhu , Xinru Li , Bo Yu , Mengqi Liu , Yan Guo","doi":"10.1016/j.ygeno.2026.111202","DOIUrl":"10.1016/j.ygeno.2026.111202","url":null,"abstract":"<div><div><em>Ustilago</em>, a pathogenic fungus, poses a serious threat to oat growth and yield. However, the species composition, abundance, and distribution of microbial communities in <em>Ustilago</em>-infected oats remain poorly characterized. In this study, we conducted 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing and biochemical assays to compare microbial profiles and physiological traits between healthy (<em>n</em> = 60) and <em>Ustilago</em>-infected oats (n = 60). Our analyses revealed higher bacterial diversity in healthy oats, particularly in the spikes and stems. Significant shifts in microbial community structure were observed across all tissues in diseased plants. While the microbiome of healthy oats predominantly comprised beneficial bacteria, including <em>Exiguobacterium indicum</em>, infected plants were largely colonized by pathogens, including <em>Ustilago hordei</em>, <em>Pyrenophora chaetomioides</em>, and <em>Curtobacterium flaccumfaciens pv</em>. <em>flaccumfaciens</em>, suggesting the occurrence of disease-driven microbial restructuring. Functional predictions indicated that enriched pathways were primarily associated with metabolism, followed by genetic information processing and environmental signal transduction. Malondialdehyde content was significantly lower in most healthy oat tissues compared to <em>Ustilago</em>-infected oats, whereas the activities of the antioxidant enzymes superoxide dismutase and peroxidase were markedly higher. These results implied that <em>Ustilago</em> infection induced severe oxidative damage to membrane systems, likely compromising the plant's ability to scavenge superoxide ions and hydrogen peroxide, thereby reducing overall plant health.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111202"},"PeriodicalIF":3.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959145","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

Comprehensive epigenetic analysis on 5-methylcytosine modification of circRNAs in the mouse cerebral ischemia model 小鼠脑缺血模型中5-甲基胞嘧啶修饰环状rna的综合表观遗传学分析。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-09 DOI: 10.1016/j.ygeno.2026.111199

Dan Xiong , Chao Zhang , Jian Xia

A growing body of research suggests that circular RNAs (circRNAs) and 5-methylcytosine (m⁵C) play crucial roles in the onset and progression of stroke. This includes their potential regulation of neuronal damage and repair under cerebral ischemic conditions. However, the specific features of m⁵C modification in circRNAs associated with stroke remain unclear. In this study, we established a mouse model of cerebral ischemia (MCAO) and utilized methylated RNA immunoprecipitation sequencing (MeRIP-Seq) to identify m⁵C peaks. In comparison to the control group, MCAO exhibited significant changes in 1982 m5C peaks, with 1096 peaks upregulated and 886 peaks downregulated. Differentially expressed genes in m5C were identified to have significant involvement in the MAPK signaling pathway, GABAergic synapse, and foxO signaling pathway. Additionally, through integrated analysis of MeRIP-Seq and RNA-Seq data, we identified 24 circRNAs that underwent significant changes in both methylation and expression. This suggests a potential association between stroke and circRNA m⁵C modification, providing insights into the prognosis of stroke patients and the identification of novel intervention targets.

越来越多的研究表明，环状rna （circRNAs）和5-甲基胞嘧啶（m5C）在中风的发生和发展中起着至关重要的作用。这包括它们在脑缺血条件下对神经元损伤和修复的潜在调节。然而，与卒中相关的circrna中m5C修饰的具体特征仍不清楚。在这项研究中，我们建立了脑缺血（MCAO）小鼠模型，并利用甲基化RNA免疫沉淀测序（MeRIP-Seq）鉴定m5C峰。与对照组相比，MCAO在1982个m5C峰发生了显著变化，其中1096个峰上调，886个峰下调。m5C中差异表达的基因与MAPK信号通路、gaba能突触和foxO信号通路相关。此外，通过MeRIP-Seq和RNA-Seq数据的综合分析，我们确定了24个circrna在甲基化和表达方面都发生了显著变化。这表明卒中与circRNA m5C修饰之间存在潜在关联，为卒中患者的预后和确定新的干预靶点提供了见解。

{"title":"Comprehensive epigenetic analysis on 5-methylcytosine modification of circRNAs in the mouse cerebral ischemia model","authors":"Dan Xiong , Chao Zhang , Jian Xia","doi":"10.1016/j.ygeno.2026.111199","DOIUrl":"10.1016/j.ygeno.2026.111199","url":null,"abstract":"<div><div>A growing body of research suggests that circular RNAs (circRNAs) and 5-methylcytosine (m<sup>5</sup>C) play crucial roles in the onset and progression of stroke. This includes their potential regulation of neuronal damage and repair under cerebral ischemic conditions. However, the specific features of m<sup>5</sup>C modification in circRNAs associated with stroke remain unclear. In this study, we established a mouse model of cerebral ischemia (MCAO) and utilized methylated RNA immunoprecipitation sequencing (MeRIP-Seq) to identify m<sup>5</sup>C peaks. In comparison to the control group, MCAO exhibited significant changes in 1982 m5C peaks, with 1096 peaks upregulated and 886 peaks downregulated. Differentially expressed genes in m5C were identified to have significant involvement in the MAPK signaling pathway, GABAergic synapse, and foxO signaling pathway. Additionally, through integrated analysis of MeRIP-Seq and RNA-Seq data, we identified 24 circRNAs that underwent significant changes in both methylation and expression. This suggests a potential association between stroke and circRNA m<sup>5</sup>C modification, providing insights into the prognosis of stroke patients and the identification of novel intervention targets.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111199"},"PeriodicalIF":3.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951219","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