Projects per year
Abstract
Operons are transcriptional modules that allow bacteria to adapt to environmental changes by coordinately expressing the relevant set of genes. In humans, biological pathways and their regulation are more complex. If and how human cells coordinate the expression of entire biological processes is unclear. Here, we capture 31higher-order co-regulation modules, which we term progulons, by help of supervised machine-learning on proteomics data. Progulons consist of dozens to hundreds of proteins that together mediate core cellular functions. They are not restricted to physical interactions or co-localisation. Progulon abundance changes are primarily controlled at the level of protein synthesis and degradation. Implemented as a web app at www.proteomehd.net/progulonFinder, our approach enables the targeted search for progulons of specific cellular processes. We use it to identify a DNA replication progulon and reveal multiple new replication factors, validated by extensive phenotyping of siRNA-induced knockdowns. Progulons provide a new entry point into the molecular understanding of biological processes.
Original language | English |
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Article number | e9503 |
Number of pages | 14 |
Journal | Molecular Systems Biology |
Volume | 19 |
Issue number | 5 |
Early online date | 9 Mar 2023 |
DOIs | |
Publication status | Published - 9 May 2023 |
Keywords / Materials (for Non-textual outputs)
- DNA replication
- machine-learning
- mRNA coexpression
- protein co-regulation
- quantitative proteomics
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Protein structures in the context of time and space by mass spectrometry
1/06/14 → 31/05/21
Project: Research