Higher‐order modular regulation of the human proteome

Georg Kustatscher*, Martina Hödl, Edward Rullmann, Piotr Grabowski, Emmanuel Fiagbedzi, Anja Groth*, Juri Rappsilber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 languageEnglish
Article numbere9503
Number of pages14
JournalMolecular Systems Biology
Issue number5
Early online date9 Mar 2023
Publication statusPublished - 9 May 2023

Keywords / Materials (for Non-textual outputs)

  • DNA replication
  • machine-learning
  • mRNA coexpression
  • protein co-regulation
  • quantitative proteomics


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