Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.
Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.
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DOI：
10.1186/1755-8794-6-13
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发表时间：
2013-04-10
影响因子：
2.7
通讯作者：
Wagner DR
中科院分区：
文献类型：
--
作者：
Azuaje F;Zhang L;Jeanty C;Puhl SL;Rodius S;Wagner DR
本研究旨在通过应用基于系统的方法来扩展对心肌梗死（MI）复杂过程的认识。我们从源自MI小鼠模型的微阵列数据生成了基因共表达网络。我们根据连接模式和独立的生物信息对其进行了表征。在疾病分类模型的背景下评估了最高预测的潜在临床新奇和相关性。使用来自小鼠和人样品的独立基因表达数据验证模型。基因共表达网络由178个基因和7298个关联组成。该网络被解剖成高度互连和共表达基因的统计学和生物学意义的社区。在最重要的群落中，有一个明显与MI后心脏修复的分子事件相关（P < 0.05）。Col 5a 2是一种以前与MI反应无关但与经典型Ehlers-Danlos综合征有关的基因，发现在该群体中有许多强有力的共表达关联（11个关联ρ > 0.85）。为了验证这一发现的潜在临床应用，我们在小鼠和人类独立生成的MI数据集上测试了其疾病区分能力。在这些评价中实现了高分类准确性和一致性，接收操作特征曲线下的面积大于0.8。基于网络的方法可以发现准确和强大的临床有趣的预测见解。Col 5a 2在MI中显示出预测潜力，并且原则上可能代表用于识别和治疗缺血性心血管疾病的新的候选标记物。
This study aims to expand knowledge of the complex process of myocardial infarction (MI) through the application of a systems-based approach. We generated a gene co-expression network from microarray data originating from a mouse model of MI. We characterized it on the basis of connectivity patterns and independent biological information. The potential clinical novelty and relevance of top predictions were assessed in the context of disease classification models. Models were validated using independent gene expression data from mouse and human samples. The gene co-expression network consisted of 178 genes and 7298 associations. The network was dissected into statistically and biologically meaningful communities of highly interconnected and co-expressed genes. Among the most significant communities, one was distinctly associated with molecular events underlying heart repair after MI (P < 0.05). Col5a2, a gene previously not specifically linked to MI response but responsible for the classic type of Ehlers-Danlos syndrome, was found to have many and strong co-expression associations within this community (11 connections with ρ > 0.85). To validate the potential clinical application of this discovery, we tested its disease discriminatory capacity on independently generated MI datasets from mice and humans. High classification accuracy and concordance was achieved across these evaluations with areas under the receiving operating characteristic curve above 0.8. Network-based approaches can enable the discovery of clinically-interesting predictive insights that are accurate and robust. Col5a2 shows predictive potential in MI, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Wagner DR