The proteomic landscape of genome-wide genetic perturbations
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Christoph Messner Vadim Demichev Julia Muenzner Simran Aulakh Natalie Barthel Annika Röhl Lucía Herrera-Domínguez Anna-Sophia Egger Stephan Kamrad Jing Hou Guihong Tan Oliver Lemke Enrica Calvani Lukasz Szyrwiel Michael Mülleder Kathryn S Lilley Charles Boone Georg Kustatscher Markus RalserAbstract
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.
Journal details
Journal
Cell
Volume
186
Issue number
9
Pages
2018-2034.e21
Available online
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Full text links
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10.1016/j.cell.2023.03.026
Europe PubMed Central
37080200
Pubmed
37080200
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The publication was previously a preprint.
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