Department of Laboratories, Unit of Parasitology and Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Int J Mol Sci. 2020 Aug 30;21(17):6274. doi: 10.3390/ijms21176274.
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by behavioral alterations and currently affect about 1% of children. Significant genetic factors and mechanisms underline the causation of ASD. Indeed, many affected individuals are diagnosed with chromosomal abnormalities, submicroscopic deletions or duplications, single-gene disorders or variants. However, a range of metabolic abnormalities has been highlighted in many patients, by identifying biofluid metabolome and proteome profiles potentially usable as ASD biomarkers. Indeed, next-generation sequencing and other omics platforms, including proteomics and metabolomics, have uncovered early age disease biomarkers which may lead to novel diagnostic tools and treatment targets that may vary from patient to patient depending on the specific genomic and other omics findings. The progressive identification of new proteins and metabolites acting as biomarker candidates, combined with patient genetic and clinical data and environmental factors, including microbiota, would bring us towards advanced clinical decision support systems (CDSSs) assisted by machine learning models for advanced ASD-personalized medicine. Herein, we will discuss novel computational solutions to evaluate new proteome and metabolome ASD biomarker candidates, in terms of their recurrence in the reviewed literature and laboratory medicine feasibility. Moreover, the way to exploit CDSS, performed by artificial intelligence, is presented as an effective tool to integrate omics data to electronic health/medical records (EHR/EMR), hopefully acting as added value in the near future for the clinical management of ASD.
自闭症谱系障碍(ASD)是一种神经发育障碍,其特征为行为改变,目前影响约 1%的儿童。显著的遗传因素和机制说明了 ASD 的病因。事实上,许多受影响的个体被诊断为染色体异常、亚微观缺失或重复、单基因疾病或变体。然而,许多患者的生物流体代谢组和蛋白质组谱中都存在一系列代谢异常,这些异常谱可作为 ASD 的生物标志物。实际上,下一代测序和其他组学平台,包括蛋白质组学和代谢组学,已经揭示了早期疾病生物标志物,这些标志物可能会导致新的诊断工具和治疗靶点,这些靶点可能会因患者的特定基因组和其他组学发现而有所不同。随着越来越多的新蛋白和代谢物被鉴定为候选生物标志物,结合患者的遗传和临床数据以及环境因素(包括微生物群),我们将朝着先进的临床决策支持系统(CDSS)迈进,这些系统由机器学习模型辅助,用于先进的 ASD 个体化医疗。在此,我们将讨论新型计算方法,用于评估新的蛋白质组和代谢组 ASD 生物标志物候选物,从文献和实验室医学的角度评估其重现性和可行性。此外,还介绍了人工智能执行的 CDSS 利用方式,这是一种将组学数据整合到电子健康/医疗记录(EHR/EMR)中的有效工具,有望在不久的将来为 ASD 的临床管理提供附加价值。