The proteomic landscape of genome-wide genetic perturbations

Functional genomic strategies have become fundamental for annotating gene function and regulatory net-works. 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.

Automated summary

Functional genomic strategies are crucial for gene function annotation and regulatory network analysis. In this study, we integrated functional genomics with proteomics to quantify protein abundances in a large-scale knockout library of Saccharomyces cerevisiae using data-independent acquisition mass spectrometry. Our findings indicate that global protein expression is influenced by a complex interplay of biological and functional properties, and functional proteomics can complement current gene annotation strategies. This study provides insights into the principles governing protein expression and offers a valuable resource for functional annotation.