Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea.
Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea.
复制标题
DOI：
10.1016/j.sleep.2014.01.010
复制
发表时间：
2014-05
期刊：
影响因子：
4.8
通讯作者：
Gozal D
中科院分区：
文献类型：
--
作者：
Becker L;Kheirandish-Gozal L;Peris E;Schoenfelt KQ;Gozal D
尿蛋白质组的内在差异限制了蛋白质组学分析的鉴别能力，并使儿科睡眠障碍背景下的潜在生物标志物检测复杂化。使用严格的尿蛋白质组学分析工作流程，我们证明了性别和昼夜效应构成了健康儿童变异的两个重要来源。在疾病的背景下，复杂的病理生理扰动放大了这些蛋白质组学差异，因此需要情境化的生物标志物分析。事实上，通过以性别和昼夜依赖性方式进行生物标志物发现，我们确定了约30倍的儿童阻塞性睡眠呼吸暂停（OSA）候选生物标志物，这是一种在儿童中非常普遍的疾病，其特征是反复发作的间歇性缺氧和高碳酸血症，以及睡眠期间复发性上呼吸道阻塞事件背景下的睡眠片段。值得注意的是，生物标志物对性别和采样时间具有高度特异性，因为在早晨和睡前样本中，在男孩和女孩中鉴定的蛋白质中观察到的重叠性较差（约3%）。由于没有临床基础来解释OSA或健康儿童的性别特异性效应是显而易见的，我们建议实施情境化生物标志物策略将适用于广泛的人类疾病，并可能特别适用于儿科OSA。
Intrinsic variance of the urine proteome limits the discriminative power of proteomic analysis and complicates potential biomarker detection in the context of pediatric sleep disorders. Using a rigorous workflow for proteomic analysis of urine, we demonstrate that gender and diurnal effects constitute two important sources of variability in healthy children. In the context of disease, complex pathophysiological perturbations magnify these proteomic differences and therefore require contextualized biomarker analysis. Indeed, by performing biomarker discovery in a gender and diurnal-dependent manner, we identified ~30-fold more candidate biomarkers of pediatric obstructive sleep apnea (OSA), a highly prevalent condition in children characterized by repetitive episodes of intermittent hypoxia and hypercapnia, and sleep fragmentation in the context of recurrent upper airway obstructive events during sleep. Remarkably, biomarkers were highly specific for gender and sampling time since poor overlap (~3%) was observed in the proteins identified in boys and girls across morning and bedtime samples. Since no clinical basis to explain gender-specific effects in OSA or healthy children is apparent, we propose that implementation of contextualized biomarker strategies will be applicable to a broad range of human diseases, and may be specifically applicable to pediatric OSA.
登录
查看更多内容
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
17.1
作者：
Leary RJ;Kinde I;Diehl F;Schmidt K;Clouser C;Duncan C;Antipova A;Lee C;McKernan K;De La Vega FM;Kinzler KW;Vogelstein B;Diaz LA Jr;Velculescu VE
通讯作者：
Velculescu VE
DOI：
10.1111/j.1442-200x.2010.03253.x
发表时间：
2011-02
期刊：
Pediatrics international : official journal of the Japan Pediatric Society
影响因子：
--
作者：
Kentsis A
通讯作者：
Kentsis A
影响因子：
8
作者：
Montgomery-Downs, HE;O'Brien, LM;Gozal, D
通讯作者：
Gozal, D
DOI：
10.1164/rccm.200711-1670oc
发表时间：
2008-05-15
影响因子：
24.7
作者：
Gozal, David;Capdevila, Oscar Sans;Kheirandish-Gozal, Leila
通讯作者：
Kheirandish-Gozal, Leila