Table_1_Cell Type-Specific Gene Network-Based Analysis Depicts the Heterogeneity of Autism Spectrum Disorder.XLSX

Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder characterized by substantial heterogeneity. To identify the convergence of disease pathology on common pathways, it is essential to understand the correlations among ASD candidate genes and study shared molecular pathways between them. Investigating functional interactions between ASD candidate genes in different cell types of normal human brains may shed new light on the genetic heterogeneity of ASD. Here we apply cell type-specific gene network-based analysis to analyze human brain nucleus gene expression data and identify cell type-specific ASD-associated gene modules. ASD-associated modules specific to different cell types are relevant to different gene functions, for instance, the astrocytes-specific module is involved in functions of axon and neuron projection guidance, GABAergic interneuron-specific modules are involved in functions of postsynaptic membrane, extracellular matrix structural constituent, and ion transmembrane transporter activity. Our findings can promote the study of cell type heterogeneity of ASD, providing new insights into the pathogenesis of ASD. Our method has been shown to be effective in discovering cell type-specific disease-associated gene expression patterns and can be applied to other complex diseases.自闭症谱系障碍（Autism Spectrum Disorder, ASD）是一类具有显著异质性的复杂神经精神疾病。为明确疾病病理在共同通路上的汇聚特征，探究自闭症谱系障碍候选基因间的关联并解析其共有的分子通路至关重要。在正常人类大脑的不同细胞类型中，探究自闭症谱系障碍候选基因间的功能互作，或可为该疾病的遗传异质性研究提供新视角。本研究采用基于细胞类型特异性基因网络的分析（cell type-specific gene network-based analysis）方法，对人类大脑细胞核基因表达数据进行分析，并筛选出细胞类型特异性的自闭症谱系障碍关联基因模块。不同细胞类型特异性的自闭症谱系障碍关联模块对应不同的基因功能：例如，星形胶质细胞（astrocytes）特异性模块参与轴突与神经元投射导向相关功能；γ-氨基丁酸能中间神经元（GABAergic interneuron）特异性模块则涉及突触后膜（postsynaptic membrane）、细胞外基质结构组成（extracellular matrix structural constituent）以及离子跨膜转运活性（ion transmembrane transporter activity）相关功能。本研究结果可推动自闭症谱系障碍细胞类型异质性的相关研究，为阐明其发病机制提供新的见解。本研究所用方法在筛选细胞类型特异性疾病关联基因表达模式方面已被证实有效，且可推广应用于其他复杂疾病的研究。