Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Division of Cardiology, University of Washington, Seattle, WA 98195, USA.
Cell. 2020 Oct 1;183(1):269-283.e19. doi: 10.1016/j.cell.2020.08.036. Epub 2020 Sep 10.
Determining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from over 12,000 genes across 32 normal human tissues. Tissue-specific or tissue-enriched proteins were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode tissue-specific proteins. Discordance of RNA and protein enrichment revealed potential sites of synthesis and action of secreted proteins. The tissue-specific distribution of proteins also provides an in-depth view of complex biological events that require the interplay of multiple tissues. Most importantly, our study demonstrated that protein tissue-enrichment information can explain phenotypes of genetic diseases, which cannot be obtained by transcript information alone. Overall, our results demonstrate how understanding protein levels can provide insights into regulation, secretome, metabolism, and human diseases.
确定每种组织中的蛋白质水平以及它们与 RNA 水平的比较对于理解人类生物学和疾病以及控制蛋白质水平的调节过程非常重要。我们对 32 种正常人体组织中超过 12000 个基因的相对蛋白质水平进行了定量分析。鉴定了组织特异性或组织丰富的蛋白质,并与转录组数据进行了比较。许多普遍存在的转录本被发现编码组织特异性蛋白质。RNA 和蛋白质丰度的不一致揭示了分泌蛋白的潜在合成和作用部位。蛋白质的组织特异性分布还提供了对需要多种组织相互作用的复杂生物学事件的深入了解。最重要的是,我们的研究表明,蛋白质组织富集信息可以解释遗传疾病的表型,而仅通过转录信息是无法获得的。总的来说,我们的研究结果表明,了解蛋白质水平如何为调节、分泌组、代谢和人类疾病提供见解。