Proteome effects of genome-wide single gene perturbations

Protein abundance is controlled at the transcriptional, translational and post-translational levels, and its regulatory principles are starting to emerge. Investigating these principles requires large-scale proteomics data and cannot just be done with transcriptional outcomes that are commonly used as a proxy for protein abundance. Here, we determine proteome changes resulting from the individual knockout of 3308 nonessential genes in the yeast Schizosaccharomyces pombe. We use similarity clustering of global proteome changes to infer gene functionality that can be extended to other species, such as humans or baker's yeast. Furthermore, we analyze a selected set of deletion mutants by paired transcriptome and proteome measurements and show that upregulation of proteins under stable transcript expression utilizes optimal codons.

Automated summary

The regulation of protein abundance involves transcriptional, translational, and post-translational processes. Large-scale proteomics data is required to study these regulatory principles, which cannot be accurately inferred from transcriptional outcomes alone. In this study, we investigated proteome changes resulting from the knockout of 3308 nonessential genes in the yeast Schizosaccharomyces pombe. By clustering global proteome changes, we inferred gene functionality that could be applicable to other species. Additionally, our analysis of selected deletion mutants revealed that upregulated proteins utilize optimal codons under stable transcript expression.