Chen David P, Weber Susan C, Constantinou Philip S, Ferris Todd A, Lowe Henry J, Butte Atul J
Stanford Medical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5479, USA.
Pac Symp Biocomput. 2008:243-54.
Traditionally, the elucidation of genes involved in maturation and aging has been studied in a temporal fashion by examining gene expression at different time points in an organism's life as well as by knocking out, knocking in, and mutating genes thought to be involved. Here, we propose an in silico method to combine clinical electronic medical record (EMR) data and gene expression measurements in the context of disease to identify genes that may be involved in the process of human maturation and aging. First we show that absolute lymphocyte count may serve as a biomarker for maturation by using statistical methods to compare trends among different clinical laboratory tests in response to an increase in age. We then propose using the rate of decay for absolute lymphocyte count across 12 diseases as a proxy for differences in aging. We correlate the differing rates with gene expression across the same diseases to find maturation/aging related genes. Among the 53 genes with strongest correlations between expression profile and change in rate of decay, we found genes previously implicated in the process of aging, including MGMT (DNA repair), TERF2 (telomere stability), POLD1 (DNA replication and repair), and POLG (mtDNA replication).
传统上，对参与成熟和衰老过程的基因的阐释一直是通过在生物体生命的不同时间点检测基因表达，以及通过敲除、敲入和突变被认为与之相关的基因，以时间顺序的方式进行研究的。在此，我们提出一种计算机模拟方法，将临床电子病历（EMR）数据与疾病背景下的基因表达测量相结合，以识别可能参与人类成熟和衰老过程的基因。首先，我们通过使用统计方法比较不同临床实验室检测指标随年龄增长的变化趋势，表明绝对淋巴细胞计数可作为成熟的生物标志物。然后，我们提出将12种疾病中绝对淋巴细胞计数的衰减率作为衰老差异的替代指标。我们将不同的衰减率与相同疾病中的基因表达进行关联，以寻找与成熟/衰老相关的基因。在表达谱与衰减率变化之间相关性最强的53个基因中，我们发现了先前与衰老过程相关的基因，包括MGMT（DNA修复）、TERF2（端粒稳定性）、POLD1（DNA复制和修复）和POLG（线粒体DNA复制）。
