The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Correct Interpretation of Comprehensive Phosphorylation Dynamics Requires Normalization by Protein Expression Changes
Open accessAbstract
The interpretation of quantitative phosphoproteomics studies is complicated because each differential phosphorylation event integrates both changes in protein expression and phosphorylation. Here we investigated this phenomenon by performing parallel comparisons of protein expression and phosphorylation in S. cerevisiae. In each of two experiments comparing yeast mutants bearing deletions in FUS3 or STE7 with their wild-type counterparts, we quantified over 4100 proteins, including all members of the yeast mating pathway. We also identified 12,499 unique phosphorylation sites in this work. We demonstrate the critical importance of controlling the protein-level false-discovery rate and provide a novel method to assess the accuracy of protein false-discovery rate estimates. For the first time, 96% of nonredundant phosphopeptide ratios could be calibrated by protein levels, allowing truly differential phosphorylation to be distinguished from altered protein expression. This revealed a starkly different view, with 25% of seemingly differential phosphopeptides now attributed to changes in protein expression. Combined protein expression and phosphorylation surveys uncovered both independent and concerted changes in protein expression and phosphorylation, while highlighting the partially redundant role of a second MAPK (Kss1) in the mating pathway.
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Self-citationGlobal analysis of protein expression in yeast
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Self-citationSemi-supervised learning for peptide identification from shotgun proteomics datasets
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Self-citationComprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast
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Self-citationA dual pressure linear ion trap orbitrap instrument with very high sequencing speed
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Quantitative Analysis of Synaptic Phosphorylation and Protein Expression
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Cited by
Next-generation proteomics: towards an integrative view of proteome dynamics
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Estimating the total number of phosphoproteins and phosphorylation sites in eukaryotic proteomes
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Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome
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Metadata
- Authors
- Wu, R., Dephoure, N., Haas, W., Huttlin, E. L., Zhai, B., Sowa, M. E., & Gygi, S. P.
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 10
- Issue
- 8
- Pages
- M111.009654
- ISSN
- 1535-9476 (ISSN-L)
- OpenAlex
- W2038801176
- Cited by
- 176
- References
- 10
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
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