Kosti Idit, Jain Nishant, Aran Dvir, Butte Atul J, Sirota Marina
Institute for Computational Health Sciences, University of California, San Francisco, California, United States of America.
Sci Rep. 2016 May 4;6:24799. doi: 10.1038/srep24799.
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.
分子生物学的中心法则描述了从信使核糖核酸(mRNA)到蛋白质的遗传信息翻译过程,但并未明确该过程在整个基因组中的定量或时间安排。我们分析了多种人类组织中的蛋白质和基因表达情况。为了研究基因和蛋白质表达的一致性与不一致性,我们整合了人类蛋白质组图谱项目的质谱数据以及基因型-组织表达项目的RNA测序测量数据。我们分析了近200个样本中14种组织类型的16561个基因及相应蛋白质。一项全面的组织和基因特异性分析显示,在这14种组织中,mRNA与蛋白质表达之间的相关性为正,范围在0.36至0.5之间。我们还鉴定出1012个在所有组织中RNA和蛋白质表达都相关的基因,并研究了每个感兴趣组织中表达一致和不一致的基因与蛋白质。我们进一步扩展分析,寻找与正常组织相比在癌症中差异相关的基因和蛋白质,结果显示正常组织中的相关性更高。最后,我们在生物标志物和药物靶点发现的背景下探讨了这些发现的意义。