Dominant Processes during Human Dendritic Cell Maturation Revealed by Integration of Proteome and Transcriptome at the Pathway Level
Dominant Processes during Human Dendritic Cell Maturation Revealed by Integration of Proteome and Transcriptome at the Pathway Level
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DOI：
10.1021/pr9008546
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发表时间：
2010-04-01
影响因子：
4.4
通讯作者：
Cavalieri, Duccio
中科院分区：
文献类型：
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作者：
Buschow, Sonja I.;Lasonder, Edwin;Cavalieri, Duccio
基因表达通常用于研究树突状细胞（DC）的活化以鉴定决定这些细胞是否诱导免疫刺激性或致耐受性免疫应答的蛋白质。然而，RNA表达并不一定能预测蛋白质丰度，并且通常需要大量的实验来获得统计学显著性。蛋白质组学提供了对蛋白质表达的直接观察，但成本高且耗时。在这里，我们结合了一个全面的定量蛋白质组和转录组分析的一批未成熟和细胞因子鸡尾酒成熟的人DC和整合所得的数据集在通路水平。尽管差异mRNA和蛋白质表达之间的总体相关性较低，但DC相关通路组分之间的相关性显著较高。差异表达的蛋白质和基因部分映射到相同的，但也不同的途径组件，表明RNA和蛋白质的数据不仅支持，而且相互补充。我们确定了5个主要途径，这证实了细胞因子，细胞粘附和迁移在DC成熟中的重要性，也表明了脂质代谢的基本作用。从这些途径中，我们提取了可能改善DC疫苗设计的新的成熟标志物。对于几个候选标志物，我们确认了检查来自多个个体的DC的广泛意义，强调了我们方法的有效性。我们的结论是，整合不同的，但相关的数据集在通路水平可以显着提高多“组学”分析的预测能力。
Gene expression is commonly used to study the activation of dendritic cells (DCs) to identify proteins that determine whether these cells induce an immunostimulatory or tolerogenic immune response. RNA expression, however, does not necessarily predict protein abundance and often requires large numbers of experiments for statistical significance. Proteomics provides a direct view on protein expression but is costly and time consuming. Here, we combined a comprehensive quantitative proteome and transcriptome analysis on a single batch of immature and cytokine cocktail matured human DCs and integrated resulting data sets at the pathway level. Although overall correlation between differential mRNA and protein expression was low, correlation between components of DC relevant pathways was significantly higher. Differentially expressed proteins and genes partly mapped to identical but also to different pathway components demonstrating that RNA and protein data not only supported but also complemented each other. We identified 5 dominant pathways, which confirmed the importance of cytokines, cell adhesion, and migration in DC maturation and also indicated a fundamental role for lipid metabolism. From these pathways we extracted novel maturation markers that might improve DC vaccine design. For several of the candidate markers we confirmed widespread significance examining DCs from multiple individuals, underscoring the validity of our approach. We conclude that integration of different but related data sets at the pathway level can significantly increase the predictive power of multi "omics" analyses.