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Abstract：
Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease with no cure. Human endogenous retroviruses (HERVs) have been implicated in its pathogenesis but their relevance to ALS is not fully understood. We examined bulk RNA-seq data from almost 2,000 ALS and unaffected control samples derived from the cortex and spinal cord. Using different methods of feature selection, including differential expression analysis and machine learning, we discovered that transcription of HERV-K loci 1q22 and 8p23.1 were significantly upregulated in the spinal cord of individuals with ALS. Additionally, we identified a subset of ALS patients with upregulated HERV-K expression in the cortex and spinal cord. We also found the expression of HERV-K loci 19q11 and 8p23.1 was correlated with protein coding genes previously implicated in ALS and dysregulated in ALS patients in this study. These results clarify the association of HERV-K and ALS and highlight specific genes in the pathobiology of late-stage ALS.
摘要：
肌萎缩侧索硬化症（ALS）是一种普遍致命的神经退行性疾病，无法治愈。人内源性逆转录病毒（HERV）已涉及其发病机理，但其与ALS的相关性尚未完全了解。我们检查了来自近2,000个ALS和来自皮质和脊髓的不受影响的对照样品的大量RNA-seq数据。使用不同的特征选择方法，包括差异表达分析和机器学习，我们发现HERV-K位点1q22和8p23.1的转录在ALS患者的脊髓中显著上调.此外,我们确定了ALS患者的一个亚组在皮质和脊髓HERV-K表达上调.在这项研究中，我们还发现HERV-K基因座19q11和8p23.1的表达与先前与ALS有关的蛋白质编码基因相关，并且在ALS患者中失调。这些结果阐明了HERV-K和ALS的关联，并突出了晚期ALS病理生物学中的特定基因。
