The Johnson Center for Child Health and Development, Austin, TX, United States of America.
Departments of Mathematical Sciences and Biological Sciences, Bioinformatics & Computational Biology Program, University of Texas at Dallas, Dallas, TX, United States of America.
PLoS One. 2021 Feb 24;16(2):e0246581. doi: 10.1371/journal.pone.0246581. eCollection 2021.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Given the lack of specific pharmacological therapy for ASD and the clinical heterogeneity of the disorder, current biomarker research efforts are geared mainly toward identifying markers for determining ASD risk or for assisting with a diagnosis. A wide range of putative biological markers for ASD is currently being investigated. Proteomic analyses indicate that the levels of many proteins in plasma/serum are altered in ASD, suggesting that a panel of proteins may provide a blood biomarker for ASD. Serum samples from 76 boys with ASD and 78 typically developing (TD) boys, 18 months-8 years of age, were analyzed to identify possible early biological markers for ASD. Proteomic analysis of serum was performed using SomaLogic's SOMAScanTM assay 1.3K platform. A total of 1,125 proteins were analyzed. There were 86 downregulated proteins and 52 upregulated proteins in ASD (FDR < 0.05). Combining three different algorithms, we found a panel of 9 proteins that identified ASD with an area under the curve (AUC) = 0.8599±0.0640, with specificity and sensitivity of 0.8217±0.1178 and 0.835±0.1176, respectively. All 9 proteins were significantly different in ASD compared with TD boys, and were significantly correlated with ASD severity as measured by ADOS total scores. Using machine learning methods, a panel of serum proteins was identified that may be useful as a blood biomarker for ASD in boys. Further verification of the protein biomarker panel with independent test sets is warranted.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交沟通和社交互动方面存在缺陷，以及行为、兴趣或活动受限、重复。鉴于目前缺乏针对 ASD 的特异性药物治疗方法，且该疾病存在临床异质性，因此当前的生物标志物研究主要集中在确定 ASD 风险的标志物或辅助诊断上。目前正在研究广泛的 ASD 潜在生物学标志物。蛋白质组学分析表明，自闭症患者血浆/血清中的许多蛋白质水平发生改变，这表明一组蛋白质可能为自闭症提供血液生物标志物。对 76 名自闭症男孩和 78 名典型发育（TD）男孩（18 个月至 8 岁）的血清样本进行分析，以确定自闭症可能的早期生物学标志物。使用 SomaLogic 的 SOMAScanTM assay 1.3K 平台进行血清蛋白质组学分析。共分析了 1125 种蛋白质。自闭症患者中有 86 种下调蛋白和 52 种上调蛋白（FDR<0.05）。通过三种不同的算法，我们发现了一组 9 种蛋白质，可识别 ASD 的曲线下面积（AUC）为 0.8599±0.0640，特异性和敏感性分别为 0.8217±0.1178 和 0.835±0.1176。与 TD 男孩相比，所有 9 种蛋白质在 ASD 中均有显著差异，且与 ADOS 总分测量的 ASD 严重程度显著相关。使用机器学习方法，确定了一组可能有用的血清蛋白质作为自闭症男孩血液生物标志物。需要进一步验证该蛋白生物标志物组与独立测试集的一致性。
