Wellcome Centre for Cell Biology

The proteomic landscape of genome-wide genetic perturbations

Kustatscher Lab – Cell.

Authors

Messner, C.B., Demichev, V., Muenzner, J., Aulakh, S.K., Barthel, N., Röhl, A., Herrera-Domínguez, L., Egger, A., Kamrad, S., Hou, J., Tan, G., Lemke, O., Calvani, E., Szyrwiel, L., Mülleder, M., Lilley, K.S., Boone, C., Kustatscher, G., and Ralser, M.

Research paper image, details in text
By combining functional genomics with proteomics, molecular phenotypes in the yeast Saccharomyces cerevisiae can be assigned at genome scale, and systems-level insights reveal principles of how gene function relates to protein expression.

Summary of Paper by Lori Koch

Proteomics is the identification and measurement of the levels of proteins in a sample. In a recent research study published in Cell, scientists in several groups spanning the Francis Crick, Charité Universitätsmedizin Berlin, Cambridge Proteomics, and including Wellcome Centre Group Leader Georg Kustatscher measured the proteome of the 4,699 strains of laboratory yeast, each lacking a functional copy of a non-essential gene. This is the largest cellular proteomics study to date, and involved state-of-the-art high-throughput mass spectrometry to identify and quantify protein levels. The measured proteomic profiles reflect the cells’ response to the lack of a specific gene and demonstrated many known interdependencies between protein abundance and cell growth, genome structure, and protein complex components. The scientists define four strategies of functional proteomics to identify novel gene functions and networks: 1. Analysing the individual proteome profile of a given yeast strain (proteome profile, PP) 2. Analysing the abundance of a specific protein across the nearly 5,000 yeast strains of which they recorded a proteome profile (reverse proteome profile (RPP) 3. Comparing the degree of similarity in the overall proteomic profiles between different strains (profile similarity, PS) and 4. Comparing the degree of similarity between the abundances of given proteins across strains (protein covariation, PC). Using any of these four methods on their own can lead to new and different types of functional insights and combining all four can lead to the assignment of potential biological functions (based on previous knowledge of well-studied genes) to nearly 79% of yeast genes. This resource provides an unprecedented view of cells at the systems-level and allows for many new hypotheses to be generated, especially involving under-studied genes.

Related links

Journal link

Kustatscher lab website

DOI