The functional landscape of the human phosphoproteome.

Autor: Ochoa D; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. ochoa@ebi.ac.uk., Jarnuczak AF; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Viéitez C; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Gehre M; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Soucheray M; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.; Department of Cellular and Molecular Pharmacology and the Quantitative Biosciences Institute, University of California San Francisco, San Francisco, CA, USA., Mateus A; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Kleefeldt AA; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Hill A; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Garcia-Alonso L; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Stein F; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Krogan NJ; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.; Department of Cellular and Molecular Pharmacology and the Quantitative Biosciences Institute, University of California San Francisco, San Francisco, CA, USA., Savitski MM; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Swaney DL; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.; Department of Cellular and Molecular Pharmacology and the Quantitative Biosciences Institute, University of California San Francisco, San Francisco, CA, USA., Vizcaíno JA; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Noh KM; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Beltrao P; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. pbeltrao@ebi.ac.uk.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2020 Mar; Vol. 38 (3), pp. 365-373. Date of Electronic Publication: 2019 Dec 09.
DOI: 10.1038/s41587-019-0344-3
Abstrakt: 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.
Databáze: MEDLINE
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