School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA.
Departments of Translational Neuroscience and Neurology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA.
Nat Commun. 2023 Jan 6;14(1):95. doi: 10.1038/s41467-022-35494-w.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.
肌萎缩侧索硬化症（ALS）是一种神经退行性疾病，其临床异质性尚不清楚，患者发病年龄、症状进展、治疗反应、疾病持续时间和合并症表现存在显著差异。我们进行了患者分层分析，以更好地了解 ALS 病理学的变异性，利用从 208 名患者中获得的死后额皮质和运动皮质转录组。基于转座元件 (TE) 表达在 ALS 中的新兴作用，我们将基因座特异性 TE 视为分层过程中的独特分子特征。在这里，我们在这个 ALS 队列中鉴定出三个独特的分子亚型，患者的生存率存在显著差异。这些结果表明，独立的疾病机制驱动了 ALS 中的一些临床异质性。
