PDF(Pubmed)
Abstract：
Recent advances in sequencing technologies provide unprecedented opportunities for epigenetic biomarker development. Particularly the DNA methylation pattern-which is modified at specific sites in the genome during cellular differentiation, aging, and disease-holds high hopes for a wide variety of diagnostic applications. While many epigenetic biomarkers have been described, only very few of them have so far been successfully translated into clinical practice and almost exclusively in the field of oncology. This discrepancy might be attributed to the different demands of either publishing a new finding or establishing a standardized and approved diagnostic procedure. This is exemplified for epigenetic leukocyte counts and epigenetic age-predictions. To ease later clinical translation, the following hallmarks should already be taken into consideration when designing epigenetic biomarkers: 1) Identification of best genomic regions, 2) pre-analytical processing, 3) accuracy of DNA methylation measurements, 4) identification of confounding parameters, 5) accreditation as diagnostic procedure, 6) standardized data analysis, 7) turnaround time, and 8) costs and customer requirements. While the initial selection of relevant genomic regions is usually performed on genome wide DNA methylation profiles, it might be advantageous to subsequently establish targeted assays that focus on specific genomic regions. Development of an epigenetic biomarker for clinical application is a long and cumbersome process that is only initiated with the identification of an epigenetic signature.
摘要：
测序技术的最新进展为表观遗传生物标志物的开发提供了前所未有的机会。特别是DNA甲基化模式-在细胞分化过程中在基因组中的特定位点被修饰，老化，和疾病对各种各样的诊断应用寄予厚望。虽然已经描述了许多表观遗传生物标志物，到目前为止，只有极少数成功转化为临床实践，几乎完全在肿瘤学领域。这种差异可能归因于发布新发现或建立标准化和批准的诊断程序的不同需求。这是表观遗传白细胞计数和表观遗传年龄预测的例证。为了简化以后的临床翻译，在设计表观遗传生物标志物时，应考虑以下标志：1）鉴定最佳基因组区域，2)分析前处理，3）DNA甲基化测量的准确性，4)识别混杂参数，5)作为诊断程序的认证，6)标准化数据分析,7）周转时间，和8)成本和客户要求。虽然相关基因组区域的初始选择通常是在全基因组DNA甲基化图谱上进行的，随后建立专注于特定基因组区域的靶向测定可能是有利的。用于临床应用的表观遗传生物标志物的开发是一个漫长而繁琐的过程,其仅由表观遗传标签的鉴定开始。
