Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps.
Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps.
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DOI：
10.1002/pmic.200900412
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发表时间：
2010-03
期刊：
影响因子：
3.4
通讯作者：
Emili, Andrew
中科院分区：
文献类型：
--
作者：
Isserlin, Ruth;Merico, Daniele;Alikhani-Koupaei, Rasoul;Gramolini, Anthony;Bader, Gary D.;Emili, Andrew
全球蛋白质表达谱可能揭示与常见心脏病相关的扰动。我们已经使用鸟枪MS/MS监测心脏组织中的生物系统的状态与疾病发作，心功能不全和进展到心力衰竭的扩张型心肌病的时程小鼠模型。然而，解释数百种差异表达蛋白的功能意义一直是具有挑战性的。在这里，我们利用改进的富集统计方法和功能相关基因集的广泛收集，获得更全面的了解与扩张型心肌病功能下降相关的进行性改变。我们将富集结果可视化为富集图，其中基于注释相似性对重要基因集进行分组。这种方法极大地简化了对大量富集基因集的解释。对于特定感兴趣的途径，如细胞凋亡和MAPK（丝裂原活化蛋白激酶）级联，我们对潜在的信号网络进行了更详细的分析，包括表达模式的实验验证。
Global protein expression profiling can potentially uncover perturbations associated with common forms of heart disease. We have used shotgun MS/MS to monitor the state of biological systems in cardiac tissue correlating with disease onset, cardiac insufficiency and progression to heart failure in a time-course mouse model of dilated cardiomyopathy. However, interpreting the functional significance of the hundreds of differentially expressed proteins has been challenging. Here, we utilize improved enrichment statistical methods and an extensive collection of functionally related gene sets, gaining a more comprehensive understanding of the progressive alterations associated with functional decline in dilated cardiomyopathy. We visualize the enrichment results as an Enrichment Map, where significant gene sets are grouped based on annotation similarity. This approach vastly simplifies the interpretation of the large number of enriched gene sets found. For pathways of specific interest, such as Apoptosis and the MAPK (mitogen-activated protein kinase) cascade, we performed a more detailed analysis of the underlying signaling network, including experimental validation of expression patterns.
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