The functional landscape of the human phosphoproteome
By D. Ochoa, Andrew F. Jarnuczak, Cristina Viéitez, Maja Gehre, Margaret Soucheray, A. Mateus, Askar A. Kleefeldt, Anthony D Hill, Luz Garcia-Alonso, F. Stein and 6 more. Nature Biotechnology, 2019
424 citations recorded by the source corpus.
Protein phosphorylation is a key post-translational modification regulating protein function in almost all cellular processes. Although tens of thousands of phosphorylation sites have been identified in human cells, approaches to determine the functional importance of each phosphosite are lacking. Here, we manually curated 112 datasets of phospho-enriched proteins, generated from 104 different human cell types or tissues. We re-analyzed the 6,801 proteomics experiments that passed our quality control criteria, creating a reference phosphoproteome containing 119,809 human phosphosites. To prioritize functional sites, we used machine learning to identify 59 features indicative of proteomic, structural, regulatory or evolutionary relevance and integrate them into a single functional score. Our approach identifies regulatory phosphosites across different molecular mechanisms, processes and diseases, and reveals genetic susceptibilities at a genomic scale. Several regulatory phosphosites were experimentally validated, including identifying a role in neuronal differentiation for phosphosites in SMARCC2, a member of the SWI/SNF chromatin-remodeling complex. Phosphorylation sites are ranked for functional relevance using a comprehensive, high-quality human phosphoproteome.
Subfields: Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f586c2871f0ec5e4f3c268e6280b94fc2ac303d1
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Citations in the corpus
- The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences (2021, background): “Previously to this more systematic effort, we reanalysed 112 human phospho-enriched datasets, generated from 104 different human cell types or tissues (51).”
- The ProteomeXchange consortium at 10 years: 2023 update (2022, methodology): “In this context, PRIDE participated in a study using ML approaches to create a functional score for human phosphosites (54), where 112 human phospho-enriched datasets were reanalysed.”
- Towards a structurally resolved human protein interaction network (2021, methodology): “We obtained a list of protein phosphorylation sites with predicted functional relevance 26 , phosphosite annotations 28 and regulation of phosphorylation sites across a large panel of conditions 29 .”