weighted gene co-expression analysis (WGCNA)

  • 文章类型: Journal Article
    饮食影响炎症性肠病(IBD)的发病机制和临床过程。地中海饮食(MD)与炎症生物标志物的减少以及与健康相关的微生物类群和代谢物的改变有关。我们旨在确定介导溃疡性结肠炎(UC)中MD与粪便钙卫蛋白(FCP)之间关系的肠道微生物组特征。使用加权基因共表达网络分析(WGCNA)来鉴定与MD和FCP相关的共富微生物类群和代谢物的模块。所考虑的特征是肠道微生物类群,血清代谢物,膳食成分,在8周内FCP增加(n=13)或减少(n=16)的参与者的短链脂肪酸和胆汁酸谱。WGCNA揭示了十个模块,其中包含十六个关键功能,这些功能充当了MD和FCP之间的关键中介。三个分类群(prausnitzii粪杆菌,Dorealongicatena,菊花Roseburiainulinivorans)和一组四种代谢物(苯甲醇,3-羟基苯基乙酸酯,3-4-羟基苯基乙酸酯和苯基乙酸酯)表现出强烈的介导作用(ACME:-1.23,p=0.004)。这项研究发现了饮食之间的新关联,炎症和肠道微生物组,为MD如何影响IBD的潜在机制提供新的见解。参见clinicaltrials.gov(NCT04474561)。
    Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-abundant microbial taxa and metabolites correlated with the MD and FCP. The features considered were gut microbial taxa, serum metabolites, dietary components, short-chain fatty acid and bile acid profiles in participants that experienced an increase (n = 13) or decrease in FCP (n = 16) over eight weeks. WGCNA revealed ten modules containing sixteen key features that acted as key mediators between the MD and FCP. Three taxa (Faecalibacterium prausnitzii, Dorea longicatena, Roseburia inulinivorans) and a cluster of four metabolites (benzyl alcohol, 3-hydroxyphenylacetate, 3-4-hydroxyphenylacetate and phenylacetate) demonstrated a strong mediating effect (ACME: -1.23, p = 0.004). This study identified a novel association between diet, inflammation and the gut microbiome, providing new insights into the underlying mechanisms of how a MD may influence IBD. See clinicaltrials.gov (NCT04474561).
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    阿尔茨海默病(AD)是一种复杂的多因素神经退行性疾病,其特征是进行性记忆丧失。该疾病的主要病理特征是淀粉样β(Aβ)斑块的细胞外沉积和由过度磷酸化tau蛋白组成的细胞内神经原纤维缠结。了解导致AD进展的因素,分子特征的数量,和治疗剂的开发在发现治疗疾病的改善疾病的药物中发挥了重要作用。生物信息学已经确立了其在许多生物学领域的意义。生物信息学在药物发现中的作用,正在显著崛起,并将继续发展。近年来,不同的生物信息学方法,viz.蛋白质信号通路,不同类别药物之间的分子特征差异,药物的相互作用及其潜在的治疗机制,已被用于确定AD的潜在治疗靶标。还发现生物信息学工具有助于发现新药,基于组学的生物标志物,和药物重新用于AD。本综述旨在探讨各种先进的生物信息学工具在靶标识别中的应用。生物标志物,通路,以及治疗这种疾病的潜在疗法。
    Alzheimer\'s disease (AD) is a complex multifactorial neurodegenerative disease characterized by progressive memory loss. The main pathological features of the disease are extracellular deposition of amyloid β (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Understanding factors contributing to AD progression, the number of molecular signatures, and the development of therapeutic agents played a significant role in the discovery of disease-modifying drugs to treat the disease. Bioinformatics has established its significance in many areas of biology. The role of bioinformatics in drug discovery, is emerging significantly and will continue to evolve. In recent years, different bioinformatics methodologies, viz. protein signaling pathway, molecular signature differences between different classes of drugs, interacting profiles of drugs and their potential therapeutic mechanisms, have been applied to identify potential therapeutic targets of AD. Bioinformatics tools were also found to contribute to the discovery of novel drugs, omics-based biomarkers, and drug repurposing for AD. The review aims to explore the applications of various advanced bioinformatics tools in the identification of targets, biomarkers, pathways, and potential therapeutics for the treatment of the disease.
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  • 文章类型: Journal Article
    作为常见的恶性肿瘤之一,前列腺腺癌(PRAD)一直是一个日益严重的健康问题,也是癌症相关死亡的主要原因。为了获得表达和功能相关的RNA,我们首先筛选了候选hubmRNA,并表征了它们与癌症的关联.鉴定了八个失调的基因,并将其用于建立风险模型(AUC在10年为0.972),该模型可能是癌症预后的特定生物标志物。然后,筛选相关的miRNAs和lncRNAs,构建的主要相互作用网络显示了不同RNA之间的潜在交叉对话。调查了IsomiR景观,以了解相关同源miRNA基因座中详细的isomiR,由于序列和表达的多样性,极大地丰富了RNA相互作用网络。我们最终将TK1、miR-222-3p和SNHG3描述为关键的RNA,异常表达模式与不良生存结局相关。TK1被发现与其他基因的合成致死相互作用,牵涉到精准医学的潜在治疗靶点。LncRNASNHG3可以海绵miR-222-3p扰乱RNA调控网络和TK1表达。这些结果表明TK1:miR-222-3p:SNHG3轴可能是潜在的预后生物标志物。这将有助于进一步了解癌症病理生理学,并为精准医学提供潜在的治疗靶点。
    As one of common malignancies, prostate adenocarcinoma (PRAD) has been a growing health problem and a leading cause of cancer-related death. To obtain expression and functional relevant RNAs, we firstly screened candidate hub mRNAs and characterized their associations with cancer. Eight deregulated genes were identified and used to build a risk model (AUC was 0.972 at 10 years) that may be a specific biomarker for cancer prognosis. Then, relevant miRNAs and lncRNAs were screened, and the constructed primarily interaction networks showed the potential cross-talks among diverse RNAs. IsomiR landscapes were surveyed to understand the detailed isomiRs in relevant homologous miRNA loci, which largely enriched RNA interaction network due to diversities of sequence and expression. We finally characterized TK1, miR-222-3p and SNHG3 as crucial RNAs, and the abnormal expression patterns of them were correlated with poor survival outcomes. TK1 was found synthetic lethal interactions with other genes, implicating potential therapeutic target in precision medicine. LncRNA SNHG3 can sponge miR-222-3p to perturb RNA regulatory network and TK1 expression. These results demonstrate that TK1:miR-222-3p:SNHG3 axis may be a potential prognostic biomarker, which will contribute to further understanding cancer pathophysiology and providing potential therapeutic targets in precision medicine.
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