RNA, Circular

RNA, 环状
  • 文章类型: Journal Article
    背景:环状RNA(circularRNAs)已被证实在疾病的发生和发展中起着至关重要的作用。探索circRNAs与疾病之间的关系对于研究病因和治疗疾病具有深远的意义。为此,基于我们以前的工作GMNN2CD中构造的图马尔可夫神经网络算法(GMNN),我们进一步考虑了影响circRNA与疾病之间关联的多源生物学数据,并基于人类肝细胞癌(HCC)组织数据开发了一个更新的网络服务器CircDA,以验证CircDA的预测结果.
    结果:CircDA建立在基于Tumarkov的深度学习框架之上。该算法将生物分子视为节点,将分子之间的相互作用视为边缘,合理地抽象多组学数据,并将它们建模为异质生物分子缔合网络,可以反映不同生物分子之间的复杂关系。使用HCC的文献资料进行案例研究,子宫颈,和胃癌表明CircDA预测因子可以识别已知的circRNAs和疾病之间缺失的关联,并采用实时荧光定量PCR(RT-qPCR)实验,发现五个circRNAs显著差异表达,这证明CircDA可以预测与新的circRNAs相关的疾病。
    结论:这种具有足够反馈的有效计算预测和案例分析使我们能够识别circRNA相关疾病和疾病相关circRNAs。我们的工作提供了一种预测circRNA相关疾病的方法,并且可以为疾病与某些circRNA的关联提供指导。为了便于使用,在线预测服务器(http://server。malab.cn/CircDA)提供,代码是开源的(https://github.com/nmt315320/CircDA。git)以方便算法改进。
    BACKGROUND: Circular RNAs (circRNAs) have been confirmed to play a vital role in the occurrence and development of diseases. Exploring the relationship between circRNAs and diseases is of far-reaching significance for studying etiopathogenesis and treating diseases. To this end, based on the graph Markov neural network algorithm (GMNN) constructed in our previous work GMNN2CD, we further considered the multisource biological data that affects the association between circRNA and disease and developed an updated web server CircDA and based on the human hepatocellular carcinoma (HCC) tissue data to verify the prediction results of CircDA.
    RESULTS: CircDA is built on a Tumarkov-based deep learning framework. The algorithm regards biomolecules as nodes and the interactions between molecules as edges, reasonably abstracts multiomics data, and models them as a heterogeneous biomolecular association network, which can reflect the complex relationship between different biomolecules. Case studies using literature data from HCC, cervical, and gastric cancers demonstrate that the CircDA predictor can identify missing associations between known circRNAs and diseases, and using the quantitative real-time PCR (RT-qPCR) experiment of HCC in human tissue samples, it was found that five circRNAs were significantly differentially expressed, which proved that CircDA can predict diseases related to new circRNAs.
    CONCLUSIONS: This efficient computational prediction and case analysis with sufficient feedback allows us to identify circRNA-associated diseases and disease-associated circRNAs. Our work provides a method to predict circRNA-associated diseases and can provide guidance for the association of diseases with certain circRNAs. For ease of use, an online prediction server ( http://server.malab.cn/CircDA ) is provided, and the code is open-sourced ( https://github.com/nmt315320/CircDA.git ) for the convenience of algorithm improvement.
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  • 文章类型: Review
    目的:我们本研究利用病例对照研究,通过文献综述和生物信息学研究来探索特定circRNAs与儿童肥胖之间的关系,并预测其可能的生物学功能。为儿童肥胖的表观遗传机制研究提供思路。
    方法:通过文献综述和qRT-PCR初步筛选与儿童肥胖相关的CircRNA。在病例对照研究中,用qRT-PCR证实了肥胖儿童(n=75)和对照个体(n=75)中的CircRNA表达。接下来是生物信息学分析,如GO分析,KEGG通路分析,和ceRNA网络构建。利用多因素logistic回归分析circRNAs对肥胖的影响。还绘制了受试者工作特征(ROC)曲线,以探讨circRNAs在小儿肥胖中的临床应用价值。
    结果:分别验证了Has_circ_0046367和hsa_circ_0000284在统计学上下调和上调,分别,在肥胖儿童的外周血单核细胞中,并显示为冠心病风险增加的独立指标[hsa_circ_0046367(OR=0.681,95%CI:0.480〜0.967)和hsa_circ_0000284(OR=1.218,95%CI:1.041〜1.424)]。hsa_circ_0046367和hsa_circ_0000284联合分析的ROC曲线下面积为0.706(95%CI:0.323~0.789)。富集分析显示,这些circRNAs积极参与神经可塑性机制,细胞分泌和信号调节。
    结论:本研究显示hsa_circ_0046367的低表达和hsa_circ_0000284的高表达是儿童肥胖的危险因素,神经可塑性机制与肥胖密切相关。
    Our present study utilized case-control research to explore the relationship between specific circRNAs and pediatric obesity through a literature review and bioinformatics and to predict their possible biological functions, providing ideas for epigenetic mechanism studies of pediatric obesity.
    CircRNAs related to pediatric obesity were preliminarily screened by a literature review and qRT-PCR. CircRNA expression in children with obesity (n = 75) and control individuals (n = 75) was confirmed with qRT-PCR in a case-control study. This was followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and ceRNA network construction. Multivariate logistic regression was utilized to analyze the effects of circRNAs on obesity. A receiver operating characteristic (ROC) curve was also drawn to explore the clinical application value of circRNAs in pediatric obesity.
    Has_circ_0046367 and hsa_circ_0000284 were separately validated to be statistically downregulated and upregulated, respectively, in the peripheral blood mononuclear cells of children with obesity and revealed as independent indicators of increased CHD risk [hsa_circ_0046367 (OR = 0.681, 95% CI: 0.480 ~ 0.967) and hsa_circ_0000284 (OR = 1.218, 95% CI: 1.041 ~ 1.424)]. The area under the ROC curve in the combined analysis of hsa_circ_0046367 and hsa_circ_0000284 was 0.706 (95% CI: 0.623 ~ 0.789). Enrichment analyses revealed that these circRNAs were actively involved in neural plasticity mechanisms, cell secretion and signal regulation.
    The present research revealed that low expression of hsa_circ_0046367 and high expression of hsa_circ_0000284 are risk factors for pediatric obesity and that neural plasticity mechanisms are closely related to obesity.
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  • 文章类型: Journal Article
    帕金森病(PD)是一种复杂的异质性疾病,涉及多种遗传和环境影响。尽管已经确定了广泛的PD危险因素和疾病症状运动阶段的临床标志物,仍然没有可靠的生物标志物可用于PD运动前早期和预测疾病进展.基于高通量RNA的生物标志物谱分析和建模可以提供一种手段来利用来自众多标志物的联合信息内容来获得诊断和预后特征。在PD生物标志物研究领域,目前,没有临床验证的基于RNA的生物标志物模型可用,但是以前的研究报道了多种人体组织和体液中RNA丰度和活性的一些与疾病相关的显著变化。这里,我们回顾了PD中非编码RNA的调控和功能的最新知识,专注于microRNAs,长链非编码RNA,和环状RNA。由于越来越多的证据表明心脏和大脑之间的功能相互作用,我们讨论了在破译参与PD进展的复杂调控网络时研究非编码RNA在器官相互作用中的作用的益处.最后,我们回顾了高通量数据集的协调和管理的重要概念,我们讨论了生物医学系统从高通量表达数据中获取和评估RNA生物标记特征的潜力。
    Parkinson\'s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.
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  • 文章类型: Journal Article
    Essential hypertension (EH) is a high prevalence with multifactorial diseases. Human studies on the impact of genes on this disease are just in the initial stage, the mechanism of gene regulation is still remains unclear. Circular RNAs (circRNAs) as a continuous cycle of covalent closure, RNA molecules added to the 3\'-5\' end covalently bound by the formation of incidental event. CircRNAs may be an important biomolecule in revealing the molecule regulate mechanisms of EH.
    The circRNAs were selected and validated with qRT-PCR followed. Our experiment was conducted with case-control studies among 200 EH participants. The t-test was used to evaluate the different expression of circRNAs and miRNAs, the significance of which was set as p < 0.05.
    The hsa_circ_0037911 expression level in EH cases were significantly higher than healthy controls (p = 0.005). There was still important significance when adjusted by logistic regression (adjusted p = 0.026). We also found that hsa_circ_0037911 was an effective marker of EH (area under curve = 0.627; p = 0.002). The levels of hsa_circ_0037911 were significantly differences in gender, BMI, smoking and drinking among EH cases. There was a positive correlation between Serum creatinine (Scr) and hsa_circ_0037911.
    Our findings suggested that higher expression hsa_circ_0037911 may be key circRNAs for EH development by changing the concentration of Scr and could be a stable biomarker for early diagnosis of EH.
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