Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada.
Proteomics. 2010 Mar;10(6):1316-27. doi: 10.1002/pmic.200900412.
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.
全球蛋白质表达谱分析有可能揭示与常见形式的心脏病相关的干扰。我们已经使用shotgun MS/MS 监测与疾病发作、心脏功能不全以及扩张型心肌病时间进程小鼠模型中向心力衰竭进展相关的心脏组织中生物系统的状态。然而，解释数百种差异表达蛋白的功能意义一直具有挑战性。在这里，我们利用改进的富集统计方法和广泛的功能相关基因集，更全面地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作为富集图谱，其中显著的基因集基于注释相似性进行分组。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，包括对表达模式的实验验证。
