Higher-order modular regulation of the human proteome
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Higher-order modular regulation of the human proteome. / Kustatscher, Georg; Hödl, Martina; Rullmann, Edward; Grabowski, Piotr; Fiagbedzi, Emmanuel; Groth, Anja; Rappsilber, Juri.
In: Molecular Systems Biology, Vol. 19, No. 5, e9503, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Higher-order modular regulation of the human proteome
AU - Kustatscher, Georg
AU - Hödl, Martina
AU - Rullmann, Edward
AU - Grabowski, Piotr
AU - Fiagbedzi, Emmanuel
AU - Groth, Anja
AU - Rappsilber, Juri
N1 - © 2023 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2023
Y1 - 2023
N2 - 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 31 higher-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.
AB - 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 31 higher-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.
U2 - 10.15252/msb.20209503
DO - 10.15252/msb.20209503
M3 - Journal article
C2 - 36891684
VL - 19
JO - Molecular Systems Biology
JF - Molecular Systems Biology
SN - 1744-4292
IS - 5
M1 - e9503
ER -
ID: 340364901