Quantitative and Qualitative Proteome Characteristics Extracted from In-Depth Integrated Genomics and Proteomics Analysis
Quantitative and Qualitative Proteome Characteristics Extracted from In-Depth Integrated Genomics and Proteomics Analysis
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DOI：
10.1016/j.celrep.2013.10.041
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发表时间：
2013-12-01
期刊：
影响因子：
8.8
通讯作者：
Guryev, Victor
中科院分区：
文献类型：
--
作者：
Low, Teck Yew;van Heesch, Sebastiaan;Guryev, Victor
蛋白质的定量和定性特征在基因组、转录组和转录后水平受到调控。在这里，我们整合了两种大鼠品系肝组织的深入转录组和蛋白质组分析，以揭示这些层内和层间的相互作用。我们获得了26，463种大鼠肝脏蛋白的肽证据。我们验证了1,195个基因预测，83个剪接事件，126个蛋白质与非同义变体，20个异构体与非同义RNA编辑。定量RNA测序和蛋白质组学数据高度相关的菌株之间，但彼此之间很差，表明广泛的非遗传调控。我们的多层次分析确定了最差异表达基因Cyp 17 a1的启动子中的基因组变体，Cyp 17 a1是先前报道的人类高血压全基因组关联研究中的热门，是SHR大鼠高血压表型的潜在贡献者。这些结果表明的权力和需要的综合分析，了解遗传控制的分子动力学和表型多样性在一个系统范围内的方式。
Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and post-transcriptional levels. Here, we integrated in-depth transcriptome and proteome analyses of liver tissues from two rat strains to unravel the interactions within and between these layers. We obtained peptide evidence for 26,463 rat liver proteins. We validated 1,195 gene predictions, 83 splice events, 126 proteins with nonsynonymous variants, and 20 isoforms with nonsynonymous RNA editing. Quantitative RNA sequencing and proteomics data correlate highly between strains but poorly among each other, indicating extensive nongenetic regulation. Our multilevel analysis identified a genomic variant in the promoter of the most differentially expressed gene Cyp17a1, a previously reported top hit in genome-wide association studies for human hypertension, as a potential contributor to the hypertension phenotype in SHR rats. These results demonstrate the power of and need for integrative analysis for understanding genetic control of molecular dynamics and phenotypic diversity in a system-wide manner.