Dataset Information

A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes

ABSTRACT: Phosphorylation of proteins on serine, threonine, and tyrosine residues is a ubiquitous post-translational modification that plays a key part of essentially every cell signaling process. It is reasonable to assume that inter-individual variation in protein phosphorylation may underlie phenotypic differences, as has been observed for practically any other molecular regulatory phenotype. However, we do not know much about the extent of inter-individual variation in phosphorylation because it is quite challenging to perform a quantitative high throughput study to assess inter-individual variation in any post-translational modification. To test our ability to address this challenge with current technology, we quantified phosphorylation levels for three fully sequenced human cell lines within a nested experimental framework, and found that genetic background is the primary determinant of phosphoproteome variation. We uncovered multiple functional, biophysical, and genetic associations with germline driven phosphopeptide variation (though the small sample size in this ‘pilot’ study limits the applicability of our genetic observations). Among these associations were variants affecting protein levels or structure, with the latter presenting, on average, a stronger effect. Interestingly, we found evidence that is consistent with a phosphopeptide variability buffering effect endowed from properties enriched within longer proteins. We also undertook a thorough technical assessment of our experimental workflow to aid further efforts. Taken together, this work provides the foundation for future work to characterize inter-individual variation in post-translational modification as well as reveals novel insights into the nature of inter-individual variation in phosphorylation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Culture

SUBMITTER: Chiaowen Hsiao

LAB HEAD: Yoav Gilad

PROVIDER: PXD008002 | Pride | 2018-10-22

REPOSITORIES: Pride

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A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes.

Engelmann Brett W BW Hsiao Chiaowen Joyce CJ Blischak John D JD Fourne Yannick Y Khan Zia Z Ford Michael M Gilad Yoav Y

Scientific reports 20180814 1

Phosphorylation of proteins on serine, threonine, and tyrosine residues is a ubiquitous post-translational modification that plays a key part of essentially every cell signaling process. It is reasonable to assume that inter-individual variation in protein phosphorylation may underlie phenotypic differences, as has been observed for practically any other molecular regulatory phenotype. However, we do not know much about the extent of inter-individual variation in phosphorylation because it is qu ...[more]

PMID: 30108239

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