Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with deficits in social communication ability and repetitive behavior. The pathophysiological events involved in the brain of this complex disease are still unclear. Methods: In this study, we aimed to profile the gene expression signatures of brain cortex of ASD patients, by using two publicly available RNA-seq studies, in order to discover new ASD-related genes. Results: We detected 1567 differentially expressed genes (DEGs) by meta-analysis, where 1194 were upregulated and 373 were downregulated genes. Several ASD-related genes previously reported were also identified. Our meta-analysis identified 235 new DEGs that were not detected using the individual RNA-seq studies used. Some of those genes, including seven DEGs (PAK1, DNAH17, DOCK8, DAPP1, PCDHAC2, and ERBIN, SLC7A7), have been confirmed in previous reports to be associated with ASD. Gene Ontology (GO) and pathways analysis showed several molecular pathways enriched by the DEGs, namely, osteoclast differentiation, TNF signaling pathway, complement and coagulation cascade. Topological analysis of protein–protein interaction of the ASD brain cortex revealed proteomics hub gene signatures: MYC, TP53, HDAC1, CDK2, BAG3, CDKN1A, GABARAPL1, EZH2, VIM, and TRAF1. We also identified the transcriptional factors (TFs) regulating DEGs, namely, FOXC1, GATA2, YY1, FOXL1, USF2, NFIC, NFKB1, E2F1, TFAP2A, HINFP. Conclusion: Novel core genes and molecular signatures involved with ASD were identified by our meta-analysis.

中文翻译：

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脑转录组RNA-Seq基因表达谱的综合分析揭示了自闭症谱系障碍中的新基因，调控子和途径

背景：自闭症谱系障碍（ASD）是一种神经发育障碍，社交沟通能力和重复行为均存在缺陷。尚不清楚这种复杂疾病的大脑所涉及的病理生理事件。方法：在这项研究中，我们旨在通过使用两项公开可用的RNA-seq研究来分析ASD患者大脑皮质的基因表达特征，以发现新的ASD相关基因。结果：我们通过荟萃分析检测了1567个差异表达基因（DEG），其中1194个上调基因和373个下调基因。还确定了先前报道的几个与ASD相关的基因。我们的荟萃分析确定了使用单独的RNA-seq研究未检测到的235个新DEG。其中一些基因，包括七个DEG（PAK1，DNAH17，DOCK8，DAPP1，PCDHAC2和ERBIN，SLC7A7已在以前的报告中确认与ASD相关。基因本体论（GO）和途径分析显示，DEG丰富了数种分子途径，即破骨细胞分化，TNF信号传导途径，补体和凝血级联反应。ASD大脑皮层蛋白质间相互作用的拓扑分析揭示了蛋白质组学中枢基因特征：MYC，TP53，HDAC1，CDK2，BAG3，CDKN1A，GABARAPL1，EZH2，VIM和TRAF1。我们还确定了调节DEG的转录因子（TFs），即FOXC1，GATA2，YY1，FOXL1，USF2，NFIC，NFKB1，E2F1，TFAP2A，HINFP。结论：我们的荟萃分析确定了与ASD相关的新核心基因和分子标记。