Age-independent co-expression of antimicrobial gene clusters in the blood of septic patients
Age-independent co-expression of antimicrobial gene clusters in the blood of septic patients
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DOI：
10.1016/j.ijantimicag.2013.04.012
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发表时间：
2013-06-01
影响因子：
10.8
通讯作者：
Bauer, Michael
中科院分区：
文献类型：
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作者：
Lindig, Sandro;Quickert, Stefanie;Bauer, Michael
最近的研究已经揭示了分析血液转录组以诊断疾病的临床潜力。然而，所得到的分子标记集包括具有不同的鲁棒性和性能的特征，这取决于训练数据的维度。因此，我们研究了大规模数据中固有的模式，并适用于脓毒症患者血液样本的特征选择。通过在相关性和富集分析中整合>300个微阵列样品，我们发现了包括绝大多数共表达基因的一般响应模式。差异表达的基因显着映射到免疫反应相关的类别，并揭示了强烈相关的上调基因与抗菌功能。使用来自丰富功能类别的>20个不相关特征的分类器平均以85%的正确分类（10倍交叉验证）进行，与相关特征相当，而单个基因在识别脓毒症患者时实现了高达83%的正确分类。然而，独立的平台间比较仅验证了这些特征的一个子集，包括抗菌簇（受试者工作特征曲线下面积>0.8）。基于这些结果，我们提出了结合相关性和丰富的功能类别的分类特征选择，以获得强大的标记候选人。这项转录组荟萃分析的结果表明，年龄无关的诊断机会，虽然需要进一步的观察和动物干预实验，以确认抗菌基因在脓毒症的相关性。(C)2013年Elsevier B.V.和国际化疗学会。All rights reserved.
Recent research has unravelled the clinical potential of profiling the blood transcriptome to diagnose diseases. However, resulting molecular marker sets comprised features with varying robustness and performance, depending on the dimension of training data. Thus, we investigated patterns that are inherent in large-scale data and suitable for feature selection in application to blood samples from septic patients. By integrating >300 microarray samples in correlation and enrichment analysis, we found general response patterns including a vast majority of co-expressed genes. Differentially expressed genes significantly mapped to immune response-associated categories and revealed strongly correlating upregulated genes related to antimicrobial functions. Classifiers using >20 uncorrelated features from enriched functional categories performed with 85% correct classification on average (10-fold cross-validation), comparable with correlated features, whilst single genes achieved up to 83% correct classifications in identifying septic patients. Independent interplatform comparison, however, validated only a subset of these features, including the antimicrobial cluster (area under the receiver operating characteristic curve >0.8). Based on these results, we propose feature selection for classification incorporating correlation and enriched functional categories to obtain robust marker candidates. Results of this transcriptomic meta-analysis suggest age-independent diagnostic opportunities, although further observational and animal interventional experiments are required to confirm the relevance of antimicrobial genes in sepsis. (C) 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.