PDF(Pubmed)
Abstract：
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common autosomal dominant muscle disorders, yet no cure or amelioration exists. The clinical presentation is diverse, making it difficult to identify the actual driving pathomechanism among many downstream events. To unravel this complexity, we performed a meta-analysis of 13 original omics datasets (in total 171 FSHD and 129 control samples). Our approach confirmed previous findings about the disease pathology and specified them further. We confirmed increased expression of former proposed DUX4 biomarkers, and furthermore impairment of the respiratory chain. Notably, the meta-analysis provides insights about so far not reported pathways, including misregulation of neuromuscular junction protein encoding genes, downregulation of the spliceosome, and extensive alterations of nuclear envelope protein expression. Finally, we developed a publicly available shiny app to provide a platform for researchers who want to search our analysis for genes of interest in the future.
摘要：
面肩肱型肌营养不良症(FSHD)是一种最常见的常染色体显性遗传性肌肉疾病,然而，没有治愈或改善存在。临床表现多样，这使得在许多下游事件中难以识别实际的驱动路径机制。为了解开这种复杂性，我们对13个原始组学数据集(总共171个FSHD和129个对照样本)进行了荟萃分析.我们的方法证实了先前关于疾病病理学的发现，并进一步说明了它们。我们证实了先前提出的DUX4生物标志物的表达增加，以及呼吸链的进一步损害。值得注意的是,荟萃分析提供了迄今为止尚未报告的途径的见解，包括神经肌肉接头蛋白编码基因的失调，剪接体的下调，和核包膜蛋白表达的广泛改变。最后,我们开发了一个公开可用的闪亮应用程序，为希望在未来搜索我们感兴趣的基因的研究人员提供一个平台。
