Xing Zhangmin, Luan Bin, Zhao Ruiying, Li Zhanbiao, Sun Guojian
Department of Rehabilitation Medicine, The People's Hospital of Liaocheng, Liaocheng, Shandong, China (mainland).
The Blood Center of Liaocheng, Liaocheng, Shandong, China (mainland).
Med Sci Monit. 2017 Feb 24;23:994-1000. doi: 10.12659/msm.899690.
BACKGROUND Cardioembolic stroke (CES), which causes 20% cause of all ischemic strokes, is associated with high mortality. Previous studies suggest that pathways play a critical role in the identification and pathogenesis of diseases. We aimed to develop an integrated approach that is able to construct individual networks of pathway cross-talk to quantify differences between patients with CES and controls. MATERIAL AND METHODS One biological data set E-GEOD-58294 was used, including 23 normal controls and 59 CES samples. We used individualized pathway aberrance score (iPAS) to assess pathway statistics of 589 Ingenuity Pathways Analysis (IPA) pathways. Random Forest (RF) classification was implemented to calculate the AUC of every network. These procedures were tested by Monte Carlo Cross-Validation for 50 bootstraps. RESULTS A total of 28 networks with AUC >0.9 were found between CES and controls. Among them, 3 networks with AUC=1.0 had the best performance for classification in 50 bootstraps. The 3 pathway networks were able to significantly identify CES versus controls, which showed as biomarkers in the regulation and development of CES. CONCLUSIONS This novel approach could identify 3 networks able to accurately classify CES and normal samples in individuals. This integrated application needs to be validated in other diseases.
心源性栓塞性卒中(CES)占所有缺血性卒中病因的20%,与高死亡率相关。先前的研究表明,信号通路在疾病的识别和发病机制中起关键作用。我们旨在开发一种综合方法,能够构建个体的信号通路相互作用网络,以量化CES患者与对照组之间的差异。
使用了一个生物数据集E-GEOD-58294,包括23名正常对照和59个CES样本。我们使用个体化信号通路异常评分(iPAS)来评估589条英 Ingenuity 通路分析(IPA)信号通路的统计学特征。实施随机森林(RF)分类以计算每个网络的曲线下面积(AUC)。这些程序通过蒙特卡罗交叉验证进行了50次重抽样测试。
在CES组和对照组之间共发现28个AUC>0.9的网络。其中,3个AUC = 1.0的网络在50次重抽样中分类性能最佳。这3个信号通路网络能够显著区分CES组与对照组,在CES的调控和发展中表现为生物标志物。
这种新方法能够识别出3个能够准确区分个体中CES和正常样本的网络。这种综合应用需要在其他疾病中进行验证。