Wu Xiaolu, Li Ran, Hong Qin, Chi Xia
Department of Child Health Care, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Psychiatry. 2022 May 12;13:886055. doi: 10.3389/fpsyt.2022.886055. eCollection 2022.
Autism spectrum disorder (ASD) is a highly genetic heterogeneous neurodevelopmental disorder, which is usually considered a heritable and heterogeneous neurodevelopmental disorder and has caused a great burden to society and families. Emerging roles of ferroptosis have been observed in neurological disorders. This study aimed to construct a diagnostic model based on ferroptosis-related genes (FRGs) to contribute to the early and precise diagnosis of childhood ASD. In the candidate FRGs, we identified 27 differentially expressed genes (DEGs) between ASD patients and typically developing (TD) controls. Four key FRGs were identified using the random forest analysis for further analysis. Utilization of the four gene expression, we constructed a diagnostic model and the AUC value in the training dataset (GSE18123) is 0.7002. We deem that a patient with a score less than 0.9904 is likely to have ASD. Three validation datasets (GSE111176, GSE113834, and GSE28521) were collected and the AUC value is 0.7442, 0.7444, and 0.6474, respectively. A multi-factor regulatory network based on four FRGs indicated that RORA, EAF1, NFYB, miR-4703-3p, and miR-6073 may play a role in the development of ASD. In addition, we found piperaquine may have the potential to be a promising drug for the treatment of ASD. Overall, we constructed a diagnostic model of childhood ASD, which could contribute to the precision diagnosis and timely treatment of childhood ASD.
自闭症谱系障碍（ASD）是一种高度遗传异质性的神经发育障碍，通常被认为是一种遗传性和异质性的神经发育障碍，给社会和家庭带来了巨大负担。铁死亡在神经疾病中的新作用已被观察到。本研究旨在构建基于铁死亡相关基因（FRGs）的诊断模型，以有助于儿童ASD的早期精确诊断。在候选FRGs中，我们鉴定出ASD患者与正常发育（TD）对照之间有27个差异表达基因（DEGs）。使用随机森林分析鉴定出四个关键FRGs用于进一步分析。利用这四个基因的表达，我们构建了一个诊断模型，训练数据集（GSE18123）中的AUC值为0.7002。我们认为得分低于0.9904的患者可能患有ASD。收集了三个验证数据集（GSE111176、GSE113834和GSE28521），其AUC值分别为0.7442、0.7444和0.6474。基于四个FRGs的多因素调控网络表明，RORA、EAF1、NFYB、miR-4703-3p和miR-6073可能在ASD的发生发展中起作用。此外，我们发现磷酸氯喹可能有潜力成为治疗ASD的一种有前景的药物。总体而言，我们构建了儿童ASD的诊断模型，这有助于儿童ASD的精确诊断和及时治疗。
