The Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London NW1 1AT, UK; Precision Proteomics Center, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, Switzerland.
The Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London NW1 1AT, UK; Charité Universitätsmedizin Berlin, Department of Biochemistry, 10117 Berlin, Germany; Department of Biochemistry, Cambridge Centre for Proteomics, University of Cambridge, Cambridge CB2 1QW, UK.
Cell. 2023 Apr 27;186(9):2018-2034.e21. doi: 10.1016/j.cell.2023.03.026. Epub 2023 Apr 19.
Functional genomic strategies have become fundamental for annotating gene function and regulatory networks. Here, we combined functional genomics with proteomics by quantifying protein abundances in a genome-scale knockout library in Saccharomyces cerevisiae, using data-independent acquisition mass spectrometry. We find that global protein expression is driven by a complex interplay of (1) general biological properties, including translation rate, protein turnover, the formation of protein complexes, growth rate, and genome architecture, followed by (2) functional properties, such as the connectivity of a protein in genetic, metabolic, and physical interaction networks. Moreover, we show that functional proteomics complements current gene annotation strategies through the assessment of proteome profile similarity, protein covariation, and reverse proteome profiling. Thus, our study reveals principles that govern protein expression and provides a genome-spanning resource for functional annotation.
功能基因组学策略已成为注释基因功能和调控网络的基础。在这里，我们通过使用数据非依赖性采集质谱法，在酿酒酵母的全基因组敲除文库中定量蛋白质丰度，将功能基因组学与蛋白质组学相结合。我们发现，全局蛋白质表达是由（1）一般生物学特性，包括翻译速率、蛋白质周转率、蛋白质复合物的形成、生长速率和基因组结构，以及（2）功能特性，如蛋白质在遗传、代谢和物理相互作用网络中的连接性之间的复杂相互作用所驱动的。此外，我们还表明，功能蛋白质组学通过评估蛋白质组图谱相似性、蛋白质共变和反向蛋白质组分析，补充了当前的基因注释策略。因此，我们的研究揭示了控制蛋白质表达的原则，并为功能注释提供了一个全基因组资源。
