Eck A, de Groot E F J, de Meij T G J, Welling M, Savelkoul P H M, Budding A E
Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
J Clin Microbiol. 2017 Jun;55(6):1720-1732. doi: 10.1128/JCM.00162-17. Epub 2017 Mar 22.
Strong evidence suggests that the gut microbiota is altered in inflammatory bowel disease (IBD), indicating its potential role in noninvasive diagnostics. However, no clinical applications are currently used for routine patient care. The main obstacle to implementing a gut microbiota test for IBD is the lack of standardization, which leads to high interlaboratory variation. We studied the between-hospital and between-platform batch effects and their effects on predictive accuracy for IBD. Fecal samples from 91 pediatric IBD patients and 58 healthy children were collected. IS-pro, a standardized technique designed for routine microbiota profiling in clinical settings, was used for microbiota composition characterization. Additionally, a large synthetic data set was used to simulate various perturbations and study their effects on the accuracy of different classifiers. Perturbations were validated in two replicate data sets, one processed in another laboratory and the other with a different analysis platform. The type of perturbation determined its effect on predictive accuracy. Real-life perturbations induced by between-platform variation were significantly greater than those caused by between-laboratory variation. Random forest was found to be robust to both simulated and observed perturbations, even when these perturbations had a dramatic effect on other classifiers. It achieved high accuracy both when cross-validated within the same data set and when using data sets analyzed in different laboratories. Robust clinical predictions based on the gut microbiota can be performed even when samples are processed in different hospitals. This study contributes to the effort to develop a universal IBD test that would enable simple diagnostics and disease activity monitoring.
有力证据表明，炎症性肠病（IBD）患者的肠道微生物群发生了改变，这表明其在非侵入性诊断中具有潜在作用。然而，目前尚无临床应用用于常规患者护理。对IBD实施肠道微生物群检测的主要障碍是缺乏标准化，这导致实验室间差异很大。我们研究了医院间和平台间的批次效应及其对IBD预测准确性的影响。收集了91例儿科IBD患者和58例健康儿童的粪便样本。IS-pro是一种为临床环境中常规微生物群分析设计的标准化技术，用于微生物群组成特征分析。此外，还使用了一个大型合成数据集来模拟各种干扰，并研究它们对不同分类器准确性的影响。在两个重复数据集中验证了干扰，一个在另一个实验室处理，另一个使用不同的分析平台。干扰类型决定了其对预测准确性的影响。平台间差异引起的实际干扰明显大于实验室间差异引起的干扰。发现随机森林对模拟和观察到的干扰都具有鲁棒性，即使这些干扰对其他分类器有显著影响。当在同一数据集中进行交叉验证以及使用在不同实验室分析的数据集时，它都能达到很高的准确性。即使样本在不同医院处理，基于肠道微生物群的可靠临床预测也可以进行。这项研究有助于开发一种通用的IBD检测方法，实现简单的诊断和疾病活动监测。
