Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.
Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.
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DOI：
10.1038/srep24799
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发表时间：
2016-05-04
影响因子：
4.6
通讯作者：
Sirota M
中科院分区：
文献类型：
--
作者：
Kosti I;Jain N;Aran D;Butte AJ;Sirota M
分子生物学的中心法则描述了遗传信息从mRNA到蛋白质的翻译，但没有指定整个基因组中这一过程的定量或时间。我们分析了多种人体组织中的蛋白质和基因表达。为了研究基因和蛋白质表达的一致性和不一致性，我们整合了来自人类蛋白质组图谱项目的质谱数据和来自基因型组织表达项目的RNA-Seq测量。我们分析了近200个样本中14种组织类型的16，561个基因和相应的蛋白质。一项全面的组织和基因特异性分析显示，在14个组织中，mRNA和蛋白质表达之间的相关性为正，范围为0.36至0.5。我们还确定了1,012个基因，其RNA和蛋白质表达在所有组织中都是相关的，并检查了每个感兴趣组织一致和不一致表达的基因和蛋白质。我们扩展了我们的分析，以寻找与正常组织相比在癌症中差异相关的基因和蛋白质，在正常组织中显示出更高水平的相关性。最后，我们探讨了这些发现在生物标志物和药物靶点发现方面的意义。
The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.