Shanthikumar Shivanthan, Neeland Melanie R, Maksimovic Jovana, Ranganathan Sarath C, Saffery Richard
Respiratory and Sleep Medicine, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, Victoria, 3052, Australia.
Respiratory Diseases, Murdoch Children's Research Institute, Melbourne, Australia.
Mol Cell Pediatr. 2020 Jul 9;7(1):7. doi: 10.1186/s40348-020-00099-0.
Biomarkers which predict future health outcomes are key to the goals of precision health. Such biomarkers do not have to be involved in the causal pathway of a disease, and their performance is best assessed using statistical tests of clinical performance and evaluation of net health impact. DNA methylation is the most commonly studied epigenetic process and represents a potential biomarker of future health outcomes. We review 25 studies in non-oncological paediatric conditions where DNA methylation biomarkers of future health outcomes are assessed. Whilst a number of positive findings have been described, the body of evidence is severely limited by issues with outcome measures, tissue-specific samples, accounting for sample cell type heterogeneity, lack of appropriate statistical testing, small effect sizes, limited validation, and no assessment of net health impact. Future studies should concentrate on careful study design to overcome these issues, and integration of DNA methylation data with other 'omic', clinical, and environmental data to generate the most clinically useful biomarkers of paediatric disease.
预测未来健康结果的生物标志物是精准健康目标的关键。此类生物标志物不一定参与疾病的因果途径，其性能最好通过临床性能的统计测试和净健康影响评估来评估。DNA甲基化是最常研究的表观遗传过程，是未来健康结果的潜在生物标志物。我们回顾了25项针对非肿瘤性儿科疾病的研究，这些研究评估了未来健康结果的DNA甲基化生物标志物。虽然已经描述了一些阳性结果，但证据主体受到以下问题的严重限制：结果测量、组织特异性样本、样本细胞类型异质性的考量、缺乏适当的统计测试、效应量小、验证有限以及未评估净健康影响。未来的研究应专注于精心设计研究以克服这些问题，并将DNA甲基化数据与其他“组学”、临床和环境数据整合，以生成最具临床实用性的儿科疾病生物标志物。
