Supporting data for "A Data Set Profiling the Multi-omic Landscape of the Prefrontal Cortex in Amyotrophic Lateral Sclerosis"

Amyotrophic lateral sclerosis is the most common motor neuron disease, which still lacks effective disease-modifying therapies. Similar to other neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, ALS pathology is presumed to propagate over time, originating from the motor cortex and spreading to other cortical regions. Exploring early disease stages is crucial to understand the causative molecular changes underlying the pathology. For this, we sampled human postmortem prefrontal cortex (PFC) tissue from Brodmann area 6, an area that exhibits only moderate pathology at the time of death, and performed a multiomic analysis of 51 sporadic ALS patients and 50 control subjects. To compare sporadic disease to genetic ALS, we additionally analyzed PFC tissue from four transgenic ALS mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS) using the same methods. This multiomic data resource includes transcriptome, small RNAome and proteome data from female and male samples, aimed at elucidating early and sex-specific ALS mechanisms, biomarkers, and drug targets.

肌萎缩侧索硬化症（Amyotrophic lateral sclerosis, ALS）是最常见的运动神经元疾病，目前仍缺乏有效的疾病修饰治疗手段。与阿尔茨海默病、帕金森病等其他神经退行性疾病类似，ALS的病理进程被认为随时间推移而进展，始发于运动皮层并向其他皮层区域扩散。探索疾病早期阶段，对阐明该病理过程背后的致病分子机制至关重要。为此，我们采集了来自布罗德曼6区（Brodmann area 6）的人类死后前额叶皮层（prefrontal cortex, PFC）组织——该区域在受试者死亡时仅表现出中度病理损伤——并对51例散发性ALS患者与50例对照受试者的样本开展多组学分析（multiomic analysis）。为对比散发性ALS与遗传性ALS的差异，我们还采用相同实验方法，分析了4种转基因ALS小鼠模型（C9orf72-、SOD1-、TDP-43-及FUS-ALS）的前额叶皮层组织。本多组学数据资源涵盖来自雌性与雄性样本的转录组（transcriptome）、小RNA组（small RNAome）及蛋白质组（proteome）数据，旨在阐明ALS早期及性别特异性的发病机制、生物标志物与药物靶点。