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TOGAR: Token-gated generative refinement for high-fidelity spatial transcriptomics and robust spatial domain clustering 用于高保真空间转录组学和鲁棒空间域聚类的令牌门控生成改进。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-19 DOI: 10.1016/j.ygeno.2025.111179
Dachen Liu , Hua Shi , Yihang Lin , Zhen Chen , Quan Zou
Spatial transcriptomics maps gene expression across tissues, yet data sparsity and noise challenge long-range dependency modeling, limiting accurate spatial domain delineation. In this study, we present TOGAR, a token-gated generative refinement model that unifies denoising, spatial enhancement, and clustering for spatial transcriptomics. Firstly, the model combines a graph convolutional network loss with a loss based on the zero-inflated negative binomial distribution to reduce noise and enhance signal clarity in sparse count data. It then employs a UGate-based diffusion backbone, which integrates token gating, gated linear attention, and rotary positional embedding for generative spatial refinement. Finally, similarity-guided averaging along diffusion trajectories provides stable spot-level estimates, and clustering of the refined representations produces spatial domains with sharp boundaries suitable for downstream analyses. We evaluate TOGAR across three spatial transcriptomics platforms. In benchmarks on twelve slices against seven popular methods, TOGAR consistently achieves or exceeds clustering accuracy, demonstrating superior stability. TOGAR effectively recovers coherent cortical layer organization, delineates fine-grained tumor subdomains associated with immune activity and extracellular matrix remodeling, and generates clearer, biologically interpretable domain boundaries. Notably, TOGAR excels in detecting extremely small and rare spatial structures, successfully identifying biologically important regions that other methods completely miss, while maintaining boundary integrity in complex multi-cluster structures and avoiding issues of over-connectivity or incomplete detection.
空间转录组学绘制跨组织的基因表达,但数据稀疏性和噪声挑战了远程依赖建模,限制了准确的空间域描绘。在这项研究中,我们提出了TOGAR,一个统一了去噪、空间增强和空间转录组聚类的标记门控生成细化模型。首先,该模型将图卷积网络损失与基于零膨胀负二项分布的损失相结合,以降低稀疏计数数据中的噪声,提高信号清晰度。然后,它采用基于gate的扩散主干,该主干集成了令牌门控、门控线性注意和旋转位置嵌入,用于生成空间细化。最后,沿着扩散轨迹的相似性引导平均提供了稳定的点水平估计,并且精细表示的聚类产生具有适合下游分析的明确边界的空间域。我们通过三个空间转录组学平台评估TOGAR。在针对7种常用方法的12个切片的基准测试中,TOGAR始终达到或超过聚类精度,显示出优越的稳定性。TOGAR有效地恢复了连贯的皮质层组织,描绘了与免疫活性和细胞外基质重塑相关的细粒度肿瘤亚域,并产生了更清晰、生物学上可解释的区域边界。值得注意的是,TOGAR在检测极小和罕见的空间结构方面表现出色,成功识别了其他方法完全遗漏的重要生物区域,同时保持了复杂多簇结构的边界完整性,避免了过度连接或检测不完整的问题。
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引用次数: 0
Comprehensive small non-coding RNA profiling reveals novel diagnostic biomarkers for primary open-angle glaucoma 全面的小非编码RNA分析揭示了原发性开角型青光眼的新诊断生物标志物。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-25 DOI: 10.1016/j.ygeno.2025.111187
Juntao Zhang , Hengqian He , Fang Wang , Huilei Yu , Bowen Liu , Jingwen Yang , Qinkang Lu
Primary open-angle glaucoma (POAG) is the most prevalent type of glaucoma, and early-stage optic neuropathy may cause visual field defects. As these early defects have minimal effects on vision, they are often overlooked, resulting in the loss of optimal treatment timing. Urgent identification of novel early diagnostic biomarkers is needed. In this study, blood samples from 30 POAG patients and 30 healthy controls were analyzed for Small Non-Coding RNAs (sncRNAs) transcriptomics and validated. We performed PANDORA-seq to profile quantitative sncRNAs signature, and a total of 169 differentially expressed sncRNAs were identified, including 147 PIWI-interacting RNAs, 10 microRNAs, and 12 transfer RNA-derived small RNAs. Functional enrichment analysis of sncRNAs target genes revealed significant involvement in key pathological processes, including apoptosis, inflammation, and intraocular pressure homeostasis. Regulatory network analysis demonstrated substantial functional overlap among different sncRNAs groups, suggesting potential cooperative roles in POAG pathogenesis. The expressions of 6 candidate sncRNAs were validated by quantitative real-time polymerase chain reaction, confirming the downregulation of tsRNA-5009b-ValCAC (p < 0.05), piR-hsa-767,596 (p < 0.05), piR-hsa-731,834 (p < 0.01) and hsa-miR-451a (p < 0.05) in POAG patients. Besides, receiver operating characteristic (ROC) curve analysis demonstrated that individual sncRNAs exhibited moderate diagnostic performance, with hsa-miR-451a showing good performance (AUC = 0.83).Our study provides novel insights into the role of sncRNAs in POAG and highlights their potential as diagnostic biomarkers for early disease detection and monitoring.
原发性开角型青光眼(POAG)是最常见的青光眼类型,早期视神经病变可引起视野缺损。由于这些早期缺陷对视力的影响很小,它们经常被忽视,导致失去最佳治疗时机。迫切需要识别新的早期诊断生物标志物。在这项研究中,对30名POAG患者和30名健康对照者的血液样本进行了小分子非编码rna (sncRNAs)转录组学分析和验证。我们通过PANDORA-seq分析了sncRNAs的定量特征,共鉴定了169个差异表达的sncRNAs,包括147个piwi相互作用rna, 10个microRNAs和12个转移rna衍生的小rna。sncRNAs靶基因的功能富集分析显示,sncRNAs靶基因参与细胞凋亡、炎症和眼压稳态等关键病理过程。调控网络分析显示,不同sncRNAs组之间存在大量功能重叠,提示在POAG发病机制中潜在的协同作用。通过实时定量聚合酶链反应验证了6个候选sncrna的表达,证实了tsRNA-5009b-ValCAC的下调(p
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引用次数: 0
OCm7G: An interpretable one-class predictor for m7G methylation sites trained with limit negative samples OCm7G:用极限阴性样本训练的m7G甲基化位点的可解释的一类预测器。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-11 DOI: 10.1016/j.ygeno.2025.111173
Fei Li , Jinbang Qin , Zhaomin Yao , Yiping Xu , Yabing Zhu , Yan Wang , Lan Huang , Wenxuan Luo , Zhiguo Wang , Fengfeng Zhou
N7-methylguanosine (m7G) is a common RNA modification linked to multiple diseases. Accurate detection of m7G sites is vital for elucidating its biological roles, but conventional methods are often laborious and costly. AI-based approaches offer alternatives, yet most rely on balanced datasets, ignoring real-world imbalances where negative samples vastly outnumber positives. This discrepancy may lead to overestimated model performance. To address this, we reconstructed independent test sets with low positive-to-negative ratios and benchmarked various models. We propose OCm7G, an ensemble of one-class classifiers with hierarchical thresholding. OCm7G achieves performance comparable to state-of-the-art methods on balanced sets and surpasses them in highly imbalanced scenarios, despite using only 52.5 % of the training data. Moreover, OCm7G offers interpretable predictions, aiding researchers in understanding model decisions. The source code and datasets are publicly available at: https://github.com/lidaosheng/OCm7G.
n7 -甲基鸟苷(m7G)是一种与多种疾病相关的常见RNA修饰。准确检测m7G位点对于阐明其生物学作用至关重要,但传统方法往往既费力又昂贵。基于人工智能的方法提供了替代方案,但大多数依赖于平衡的数据集,忽略了现实世界的不平衡,即负样本数量远远超过正样本。这种差异可能导致高估模型性能。为了解决这个问题,我们重建了具有低正负比的独立测试集,并对各种模型进行了基准测试。我们提出了OCm7G,一个具有分层阈值的单类分类器的集合。OCm7G在平衡集上实现了与最先进的方法相当的性能,并在高度不平衡的场景中超越了它们,尽管只使用了52.5 %的训练数据。此外,OCm7G提供了可解释的预测,帮助研究人员理解模型决策。源代码和数据集可以在:https://github.com/lidaosheng/OCm7G上公开获取。
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引用次数: 0
Transcriptomic analysis of distinct mantle regions in yellow- and black-shelled Asian clam (Corbicula fluminea): Identification of genes associated with Shell biomineralization and pigment deposition 亚洲黄壳和黑壳蛤不同地幔区的转录组学分析:壳生物矿化和色素沉积相关基因的鉴定。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-09 DOI: 10.1016/j.ygeno.2025.111172
Xueyan Ma , Lujie Wen , Dongpo Xu , Wu Jin , Haibo Wen , Huaishun Shen
Corbicula fluminea exhibits two distinct shell color morphs: yellow and black. This study reveals molecular mechanisms behind shell color variation in the Asian clam C. fluminea (yellow vs. black morphs) through comparative transcriptomics of edge/central mantle tissues. Transcriptome assembly identified 24, 174 annotated genes and 2, 234 novel genes. Comparative analyses revealed 238 common differentially expressed genes (DEGs) shared between the YC vs YE and BC vs BE comparisons, along with 575 DEGs in BC vs YC and 460 DEGs in BE vs YE. Transcriptomic profiling demonstrated that Biomineralization genes (calcium/organic matrix-related) showed region-specific expression, driving shell formation. Melanogenesis pathway enrichment and pigmentation genes (tyrosinase, calmodulin, sulfotransferase) may play an important role in pigmentation in C. fluminea. This study expands our understanding of shell biomineralization and pigment deposition in C. fluminea, providing important insights into the genetic and biochemical regulation of shell diversity in bivalves.
Corbicula fluminea呈现出两种不同的外壳颜色:黄色和黑色。本研究通过边缘/中心地幔组织的转录组学比较揭示了亚洲蛤(黄色与黑色变种)壳颜色变化背后的分子机制。转录组组装鉴定出24174个注释基因和2234个新基因。比较分析显示,YC与YE和BC与BE比较共有238个共同差异表达基因(DEGs), BC与YC共有575个,BE与YE共有460个。转录组学分析表明,生物矿化基因(钙/有机基质相关)表现出区域特异性表达,驱动壳的形成。黑素生成途径富集和色素沉着基因(酪氨酸酶、钙调素酶、硫转移酶)可能在氟藻色素沉着中起重要作用。本研究扩大了我们对C. fluminea贝壳生物矿化和色素沉积的认识,为双壳类贝壳多样性的遗传和生化调控提供了重要的见解。
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引用次数: 0
Transposable elements as dynamic regulators of skeletal muscle development, regeneration and aging 转座因子作为骨骼肌发育、再生和衰老的动态调节因子。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-31 DOI: 10.1016/j.ygeno.2025.111180
Meijun Song , Wenjie Duan , Duomin Liang , Dinghui Dai , Li Li , Hongping Zhang
Transposable elements (TEs), once considered “junk” DNA, constitute nearly half of the mammalian genome and can replicate and reposition within the host genome. Advances in omics technologies have improved the capture and annotation of TEs, enabling functional studies. Here, we review TEs classification, structure, regulation, and annotation methods. TEs act as regulatory elements or non-coding RNAs, influencing gene networks and cell fate. While once thought inactive in somatic cells, recent evidence suggests that TEs remain transcriptionally active in various tissues, contributing to function. Focusing on skeletal muscle development, pathological regeneration, and aging, we discuss TEs expression patterns and their potential functional. TEs exhibit stage-specific expression during muscle development and are implicated in muscle-related diseases. Building on the transposon theory of aging, we summarize the increased TEs transcription and chromatin accessibility in aging muscle. Understanding TEs in skeletal muscle biology provides insights into muscle development and age-related functional decline.
转座因子(te),曾经被认为是“垃圾”DNA,构成了哺乳动物基因组的近一半,可以在宿主基因组中复制和重新定位。组学技术的进步改善了te的捕获和注释,使功能研究成为可能。本文综述了TEs的分类、结构、规则和标注方法。te作为调控元件或非编码rna,影响基因网络和细胞命运。虽然曾被认为在体细胞中不活跃,但最近的证据表明,te在各种组织中仍保持转录活性,有助于功能。关注骨骼肌发育、病理再生和衰老,我们讨论TEs表达模式及其潜在功能。te在肌肉发育过程中表现出阶段特异性表达,并与肌肉相关疾病有关。基于转座子衰老理论,我们总结了衰老肌肉中TEs转录和染色质可及性的增加。了解骨骼肌生物学中的te有助于了解肌肉发育和与年龄相关的功能衰退。
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引用次数: 0
Genetic mechanisms and population structure of growth and development in black Tibetan sheep revealed by genome-wide association study and whole-genome resequencing 全基因组关联研究和全基因组重测序揭示了黑藏羊生长发育的遗传机制和群体结构。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-24 DOI: 10.1016/j.ygeno.2025.111181
Jiacheng Gan, Qiurong Ji, Wei Gao, Yu Zhang, Xianhua Zhang, Rengeerli Sa, Shengzhen Hou, Linsheng Gui

Background

The black Tibetan sheep is an important local livestock breed. Deciphering the genetic and molecular mechanisms governing their growth and development is crucial for breeding programs. However, research on their serum metabolome and population genetic structure remains limited.

Methods

We performed a genome-wide association study (GWAS) integrating phenotypic growth traits and the serum metabolome in a cohort of 210 black Tibetan sheep, using genomic data from single nucleotide polymorphism (SNP) chip genotyping. Additionally, population genetic structure was analyzed via whole-genome resequencing (WGR).

Results

In this study, metabolome genome-wide association study (mGWAS) at the genome-wide level yielded 3,886,784 SNPs and quantified 3267 metabolites. Among them, 56,366 SNPs and 1008 metabolites were identified as significant, and five candidate genes (ZBTB38, CDK6, ZFP36L1, PRSS53, and FHIT) related to the growth and development traits of black Tibetan sheep were screened out. Notably, two of these genes, ZFP36L1 and PRSS53, were simultaneously detected in both the GWAS of phenotypic traits and mGWAS. These genes are strongly linked to certain organic compounds, including L-leucine, L-tryptophan, and pantothenic acid. Furthermore, these genes are primarily enriched in pathways including the mTOR signaling pathway, protein digestion and absorption, regulation of fat cell differentiation, glucose metabolic process, and pantothenate and coenzyme A (CoA) biosynthesis. Concurrently, WGR-based analysis of population genetic structure revealed a close genetic relationship and low differentiation among black Tibetan sheep, white Tibetan sheep, and Euler sheep.

Conclusions

In conclusion, based on the above analysis, the genetic regions, candidate genes, and enriched pathways that may significantly affect the metabolites of black Tibetan sheep were identified. These findings bridge the gap between the genome and the phenotypic traits, as many of these metabolites are key intermediates or regulators involved in growth and development processes. Combined with the elucidated population genetic structure, this study provides a solid foundation for future research into the mechanisms driving growth and development traits in this breed.
背景:黑藏羊是当地重要的家畜品种。破译控制它们生长发育的遗传和分子机制对育种计划至关重要。然而,对其血清代谢组学和群体遗传结构的研究仍然有限。方法:利用单核苷酸多态性(SNP)芯片基因分型的基因组数据,对210只黑藏羊进行全基因组关联研究(GWAS),整合表型生长性状和血清代谢组学。此外,通过全基因组重测序(WGR)分析群体遗传结构。结果:在本研究中,代谢组全基因组关联研究(mGWAS)在全基因组水平上获得了3,886,784个snp,并量化了3267种代谢物。其中,鉴定出56,366个snp和1008个代谢物具有显著性,筛选出与黑藏羊生长发育性状相关的5个候选基因(ZBTB38、CDK6、ZFP36L1、PRSS53和FHIT)。值得注意的是,其中两个基因ZFP36L1和PRSS53在表型性状的GWAS和mGWAS中同时检测到。这些基因与某些有机化合物密切相关,包括l -亮氨酸、l -色氨酸和泛酸。此外,这些基因主要富集在mTOR信号通路、蛋白质消化和吸收、脂肪细胞分化调控、葡萄糖代谢过程以及泛酸和辅酶A (CoA)生物合成等途径中。同时,基于wgr的群体遗传结构分析显示,黑藏羊、白藏羊和欧拉羊遗传关系密切,分化程度低。结论:综上所述,在上述分析的基础上,确定了可能显著影响黑藏羊代谢产物的遗传区域、候选基因和富集途径。这些发现弥合了基因组和表型性状之间的差距,因为许多这些代谢物是参与生长和发育过程的关键中间体或调节剂。结合已阐明的群体遗传结构,为进一步研究该品种生长发育性状的驱动机制奠定了基础。
{"title":"Genetic mechanisms and population structure of growth and development in black Tibetan sheep revealed by genome-wide association study and whole-genome resequencing","authors":"Jiacheng Gan,&nbsp;Qiurong Ji,&nbsp;Wei Gao,&nbsp;Yu Zhang,&nbsp;Xianhua Zhang,&nbsp;Rengeerli Sa,&nbsp;Shengzhen Hou,&nbsp;Linsheng Gui","doi":"10.1016/j.ygeno.2025.111181","DOIUrl":"10.1016/j.ygeno.2025.111181","url":null,"abstract":"<div><h3>Background</h3><div>The black Tibetan sheep is an important local livestock breed. Deciphering the genetic and molecular mechanisms governing their growth and development is crucial for breeding programs. However, research on their serum metabolome and population genetic structure remains limited.</div></div><div><h3>Methods</h3><div>We performed a genome-wide association study (GWAS) integrating phenotypic growth traits and the serum metabolome in a cohort of 210 black Tibetan sheep, using genomic data from single nucleotide polymorphism (SNP) chip genotyping. Additionally, population genetic structure was analyzed via whole-genome resequencing (WGR).</div></div><div><h3>Results</h3><div>In this study, metabolome genome-wide association study (mGWAS) at the genome-wide level yielded 3,886,784 SNPs and quantified 3267 metabolites. Among them, 56,366 SNPs and 1008 metabolites were identified as significant, and five candidate genes (<em>ZBTB38, CDK6, ZFP36L1, PRSS53,</em> and <em>FHIT</em>) related to the growth and development traits of black Tibetan sheep were screened out. Notably, two of these genes, <em>ZFP36L1</em> and <em>PRSS53</em>, were simultaneously detected in both the GWAS of phenotypic traits and mGWAS. These genes are strongly linked to certain organic compounds, including L-leucine, L-tryptophan, and pantothenic acid. Furthermore, these genes are primarily enriched in pathways including the mTOR signaling pathway, protein digestion and absorption, regulation of fat cell differentiation, glucose metabolic process, and pantothenate and coenzyme A (CoA) biosynthesis. Concurrently, WGR-based analysis of population genetic structure revealed a close genetic relationship and low differentiation among black Tibetan sheep, white Tibetan sheep, and Euler sheep.</div></div><div><h3>Conclusions</h3><div>In conclusion, based on the above analysis, the genetic regions, candidate genes, and enriched pathways that may significantly affect the metabolites of black Tibetan sheep were identified. These findings bridge the gap between the genome and the phenotypic traits, as many of these metabolites are key intermediates or regulators involved in growth and development processes. Combined with the elucidated population genetic structure, this study provides a solid foundation for future research into the mechanisms driving growth and development traits in this breed.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111181"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843576","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
Fusobacterium nucleatum exacerbates atherosclerosis progression via ceRNA network-mediated epigenetic reprogramming 核梭杆菌通过ceRNA网络介导的表观遗传重编程加剧动脉粥样硬化的进展。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-25 DOI: 10.1016/j.ygeno.2025.111186
Keyi Zhang , Lin Liu , Peiyao Wu , Lei Zhao , Jieyu Zhou , Yafei Wu
Fusobacterium nucleatum (F. nucleatum), a key periodontal pathogen, is increasingly detected in atherosclerotic plaques, yet its epigenetic regulatory mechanisms in atherosclerosis remain enigmatic. This study investigates how F. nucleatum reshapes the non-coding RNA landscape to drive atherosclerosis progression. Periodontal infection with F. nucleatum significantly increased atherosclerotic lesion area (p < 0.001) and necrotic core ratio, while reducing collagen content (p < 0.05) in ApoE−/− mice. Whole transcriptome sequencing of arterial tissues identified 847 differentially expressed mRNAs, 16 miRNAs, 19 circRNAs, and 76 lncRNAs linked to lipid metabolism and plaque instability. Focusing on atherosclerosis-associated signaling pathways, we constructed a competing endogenous RNA (ceRNA) network in F. nucleatum-infected ApoE−/− mice. Notably, we highlighted two key regulatory axes: (circRNA5047/lncRNA Ext1)-miR-18a-3p-Cflar-Autophagy and (circRNA5047/lncRNA Ext1)-miR-669f-3p-Itpr1-Autophagy. These findings provide novel insights into the role of F. nucleatum in atherosclerosis and establish a foundation for further investigation into its underlying mechanisms.
核梭杆菌(F. nucleatum)是一种重要的牙周病原体,越来越多地在动脉粥样硬化斑块中检测到,但其在动脉粥样硬化中的表观遗传调控机制仍然是谜。本研究探讨了核梭菌如何重塑非编码RNA景观以驱动动脉粥样硬化的进展。牙周感染具核梭菌显著增加动脉粥样硬化病变面积(p -/-小鼠)。动脉组织的全转录组测序鉴定出847个差异表达mrna, 16个mirna, 19个circrna和76个lncrna与脂质代谢和斑块不稳定性有关。着眼于动脉粥样硬化相关的信号通路,我们在核核f病毒感染的ApoE-/-小鼠中构建了竞争性内源性RNA (ceRNA)网络。值得注意的是,我们强调了两个关键的调控轴:(circRNA5047/lncRNA Ext1)- mir -18a-3p- clar - autophagy和(circRNA5047/lncRNA Ext1)-miR-669f-3p-Itpr1-Autophagy。这些发现为了解核梭菌在动脉粥样硬化中的作用提供了新的见解,并为进一步研究其潜在机制奠定了基础。
{"title":"Fusobacterium nucleatum exacerbates atherosclerosis progression via ceRNA network-mediated epigenetic reprogramming","authors":"Keyi Zhang ,&nbsp;Lin Liu ,&nbsp;Peiyao Wu ,&nbsp;Lei Zhao ,&nbsp;Jieyu Zhou ,&nbsp;Yafei Wu","doi":"10.1016/j.ygeno.2025.111186","DOIUrl":"10.1016/j.ygeno.2025.111186","url":null,"abstract":"<div><div><em>Fusobacterium nucleatum (F. nucleatum),</em> a key periodontal pathogen, is increasingly detected in atherosclerotic plaques, yet its epigenetic regulatory mechanisms in atherosclerosis remain enigmatic. This study investigates how <em>F. nucleatum</em> reshapes the non-coding RNA landscape to drive atherosclerosis progression. Periodontal infection with <em>F. nucleatum</em> significantly increased atherosclerotic lesion area (<em>p</em> &lt; 0.001) and necrotic core ratio, while reducing collagen content (<em>p</em> &lt; 0.05) in <em>ApoE</em><sup><em>−/−</em></sup> mice. Whole transcriptome sequencing of arterial tissues identified 847 differentially expressed mRNAs, 16 miRNAs, 19 circRNAs, and 76 lncRNAs linked to lipid metabolism and plaque instability. Focusing on atherosclerosis-associated signaling pathways, we constructed a competing endogenous RNA (ceRNA) network in <em>F. nucleatum</em>-infected <em>ApoE</em><sup>−/−</sup> mice. Notably, we highlighted two key regulatory axes: <em>(circRNA5047/lncRNA Ext1)-miR-18a-3p-Cflar-Autophagy</em> and <em>(circRNA5047/lncRNA Ext1)-miR-669f-3p-Itpr1-Autophagy</em>. These findings provide novel insights into the role of <em>F. nucleatum</em> in atherosclerosis and establish a foundation for further investigation into its underlying mechanisms.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111186"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846479","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
RNA-Seq reveals flight-induced changes in cerebellar transcriptomic profiles of racing pigeons RNA-Seq揭示了赛鸽在飞行诱导下的小脑转录组谱变化。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-29 DOI: 10.1016/j.ygeno.2025.111188
Monika Stefaniuk-Szmukier , Tomasz Szmatoła , Anna Steg , Grzegorz Smołucha , Katarzyna Ropka-Molik
The avian cerebellum is pivotal for multisensory integration and motor control during flight, yet its molecular adaptation to prolonged exertion remains incompletely defined. We profiled cerebellar transcriptomes of ten racing pigeons before and after a 300-km homing flight using whole-transcriptome RNA sequencing. Differential expression analysis revealed robust remodeling of metabolic and proteostatic pathways, including upregulation of SLC35D2, consistent with enhanced UDP-GlcNAc flux through the hexosamine biosynthetic pathway aligned with birds' naturally high glycaemia. Increased VLDLR expression links lipid handling to the reelin signalling cascade, suggesting contributions to navigation and synaptic plasticity, whereas downregulation of HTR1F indicates region-specific serotonergic modulation with exercise. Co-expression network analysis (WGCNA) identified modules enriched for endoplasmic reticulum protein processing and stress responses (PLAA, RAD23, ERN1), alongside intensified ribosome and RNA biogenesis, reflecting an elevated demand for protein synthesis and quality control. Functional enrichment (WebGestalt,) highlighted among others ribosome biogenesis, core metabolic pathways, RNA transport. These insights contribute to understanding the genetic and molecular mechanisms underpinning avian navigation and performance, providing a foundation for further research into flight-related neurophysiology.
鸟类小脑是飞行过程中多感觉整合和运动控制的关键,但其对长时间运动的分子适应尚不完全清楚。我们使用全转录组RNA测序分析了10只赛鸽在300公里归航前后的小脑转录组。差异表达分析显示代谢和蛋白抑制途径的强大重塑,包括SLC35D2的上调,这与通过己糖胺生物合成途径增强的UDP-GlcNAc通量一致,与鸟类的天然高血糖一致。VLDLR表达的增加将脂质处理与reelin信号级联联系起来,表明对导航和突触可塑性有贡献,而HTR1F的下调表明运动对区域特异性血清素能进行调节。共表达网络分析(WGCNA)发现了内质网蛋白加工和应激反应富集的模块(PLAA, RAD23, ERN1),以及核糖体和RNA生物发生的增强,反映了对蛋白质合成和质量控制的更高需求。功能富集(WebGestalt)在其他核糖体生物发生,核心代谢途径,RNA运输中突出。这些见解有助于理解鸟类导航和行为的遗传和分子机制,为进一步研究飞行相关的神经生理学奠定基础。
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引用次数: 0
Benchmarking of single nuclei RNA-seq methods on human post-mortem brain tissue 人死后脑组织单核RNA-seq方法的标杆分析。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-24 DOI: 10.1016/j.ygeno.2025.111184
Kasra Nikouei , Elin Gruyters , Fatima Memic , Craig A. Stockmeier , Jens Hjerling-Leffler
Molecular analysis of human post-mortem brain tissue holds the promise to identify disease associated mechanisms. Single nuclei RNA-sequencing (snRNA-seq) is a powerful tool for molecular-level investigations of human brain tissue with cell type resolution. In the fast-developing field of post-mortem snRNA-seq, the samples sizes of case/control studies have drastically increased over the last years. Still, to overcome genetic variability across individuals and to investigate the many relevant brain regions that have not yet been sampled, even larger cohorts are necessary. It is thus important to benchmark snRNA-seq methods against each other on relevant tissue. We compared five such methods, 10× Genomics v3.1, 10× Genomics Flex Gene Expression, Parse Biosciences Evercode v2, PIPseq v5.0 from Fluent Biosciences (now acquired by Illumina) and Smart-seq3xpress, using fresh frozen post-mortem human forebrain tissue samples. Using tissue samples from the same three donors for all methods, our investigation revealed comparable overall technical performance among the five methods but suggests that biological variability was better captured with Smart-seq3xpress. We could not model the effect of sample quality, which limits the generalizability of our results. Thus, our study suggests that the selection of snRNA-seq method should mainly be informed by the need of specific data and practical experimental considerations such as hardware requirements, ability to multiplex, tissue quantity input requirements, and transportation of samples/tissues.
人类死后脑组织的分子分析有望确定疾病相关机制。单核rna测序(snRNA-seq)是一种具有细胞类型分辨率的人类脑组织分子水平研究的有力工具。在快速发展的死后snRNA-seq领域,病例/对照研究的样本量在过去几年中急剧增加。然而,为了克服个体间的遗传变异,并调查许多尚未采样的相关大脑区域,更大的队列是必要的。因此,在相关组织上对snRNA-seq方法进行基准测试是很重要的。我们比较了五种方法,10x Genomics v3.1, 10x Genomics Flex Gene Expression, Parse Biosciences Evercode v2, Fluent Biosciences(现已被Illumina收购)的PIPseq v5.0和smartseq3express,使用新鲜冷冻的人死后前脑组织样本。在所有方法中使用来自相同三个供体的组织样本,我们的调查显示五种方法的总体技术性能相当,但表明使用Smart-seq3xpress可以更好地捕获生物变异性。我们不能模拟样本质量的影响,这限制了我们结果的普遍性。因此,我们的研究表明,snRNA-seq方法的选择应主要考虑特定数据的需要和实际实验的考虑,如硬件要求、多路复用能力、组织数量输入要求以及样品/组织的运输。
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引用次数: 0
Single-cell RNA sequencing reveals a cellular atlas of the sheep testis 单细胞RNA测序揭示了绵羊睾丸的细胞图谱。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-29 DOI: 10.1016/j.ygeno.2025.111159
Yi Wu , Lina Zhu , Xuejiao An , Yaojing Yue
Spermatogenesis is a highly regulated biological process involving various cell types, making the accurate identification and classification of different cell populations challenging. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving cellular heterogeneity at high resolution. In this study, 10× Genomics Chromium™ scRNA-seq was employed to analyze 15,826 testicular cells from three 6-month-old sexually mature Hu sheep, and a high-resolution single-cell transcriptomic atlas was generated. Specifically, six somatic cell subtypes and five germ cell subtypes were identified, which revealed the differentiation trajectory of spermatogenesis. Notably, pseudo-time analysis suggested that Leydig cells and peritubular myoid cells may originate from a common progenitor lineage in sheep. Highly expressed genes were enriched in pathways such as cAMP signaling, PI3K-Akt, and ECM–receptor interaction. Furthermore, immunohistochemical analysis validated specific marker proteins for certain cell types. Collectively, these findings provide novel insights into spermatogenesis and serve as a valuable reference for the in vitro culture of male germ cells.
精子发生是一个高度调控的生物学过程,涉及多种细胞类型,这使得准确识别和分类不同的细胞群具有挑战性。单细胞RNA测序(scRNA-seq)已成为高分辨率解决细胞异质性的有力工具。本研究采用10x Genomics Chromium™scRNA-seq技术,对3只6月龄性成熟的湖羊的15826个睾丸细胞进行了分析,获得了高分辨率的单细胞转录组图谱。具体而言,鉴定出6种体细胞亚型和5种生殖细胞亚型,揭示了精子发生的分化轨迹。值得注意的是,伪时间分析表明,绵羊的间质细胞和小管周围肌样细胞可能起源于一个共同的祖系。高表达基因在cAMP信号、PI3K-Akt和ecm受体相互作用等通路中富集。此外,免疫组织化学分析证实了某些细胞类型的特异性标记蛋白。总的来说,这些发现为精子发生提供了新的见解,并为男性生殖细胞的体外培养提供了有价值的参考。
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引用次数: 0
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Genomics
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