Chemical proteomics decrypts the kinases that shape the dynamic human phosphoproteome
Bayer, F. P.; Mueller, J.; Kabella, N.; Abele, M.; Chang, Y.-C.; Estrada, L.; Jensen, C.; Hamood, F.; Lee, C.-Y.; Schneider, A.; The, M.; Kuster, B.
Show abstract
Mass-spectrometry-based phosphoproteomics enables the analysis of thousands of protein phosphorylation events across the human proteome. However, there is a lack of scalable, hypothesis-free, and statistically sound approaches for discovering, evaluating, and falsifying kinase::substrate relationships (KSRs). Here, we developed a new concept termed potency-coherence analysis. By measuring and integrating 17 million peptidoform-specific dose-response curves for 133 kinase inhibitors with known targets and affinities, we could critically re-evaluate published KSRs and discover thousands of potency-coherent and motif-plausible new KSRs for 96 human kinases. Application of these high-confidence KSRs enabled the estimation of kinase and signaling pathway activities in cancer patient biopsies. This unified and extendable framework has been implemented in ProteomicsDB to aid researchers in understanding the human phosphoproteome in health and disease.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Signaling and transcriptional dynamics underlying early adaptation to oncogenic BRAF inhibition 95%
- Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2 95%
- A live-cell screen for altered Erk dynamics reveals principles of proliferative control 94%
Similar papers in this journal
- Multi-scale classification decodes the complexity of the human E3 ligome 96%
- Rapidly induced drug adaptation mediates escape from BRAF inhibition in single melanoma cells 95%
- Multiplexed single-cell profiling of post-perturbation transcriptional responses to define cancer vulnerabilities and therapeutic mechanism of action 95%
Similar papers in this journal
- Mining the CRBN Target Space Redefines Rules for Molecular Glue-induced Neosubstrate Recognition 97%
- OpenCell: proteome-scale endogenous tagging enables the cartography of human cellular organization 96%
- Evolutionary-Scale Enzymology Enables Biochemical Constant Prediction Across a Multi-Peaked Catalytic Landscape 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.