Network integration of thermal proteome profiling with multi-omics data decodes PARP inhibition.
Biological Networks
Multi-omics
Proteomics
Thermal Proteome Profiling
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
07 Mar 2024
07 Mar 2024
Historique:
received:
17
01
2024
accepted:
20
02
2024
revised:
13
02
2024
medline:
8
3
2024
pubmed:
8
3
2024
entrez:
7
3
2024
Statut:
aheadofprint
Résumé
Complex disease phenotypes often span multiple molecular processes. Functional characterization of these processes can shed light on disease mechanisms and drug effects. Thermal Proteome Profiling (TPP) is a mass-spectrometry (MS) based technique assessing changes in thermal protein stability that can serve as proxies of functional protein changes. These unique insights of TPP can complement those obtained by other omics technologies. Here, we show how TPP can be integrated with phosphoproteomics and transcriptomics in a network-based approach using COSMOS, a multi-omics integration framework, to provide an integrated view of transcription factors, kinases and proteins with altered thermal stability. This allowed us to recover consequences of Poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer cells on cell cycle and DNA damage response as well as interferon and hippo signaling. We found that TPP offers a complementary perspective to other omics data modalities, and that its integration allowed us to obtain a more complete molecular overview of PARP inhibition. We anticipate that this strategy can be used to integrate functional proteomics with other omics to study molecular processes.
Identifiants
pubmed: 38454145
doi: 10.1038/s44320-024-00025-w
pii: 10.1038/s44320-024-00025-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
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