PXD008002

PXD008002 is an original dataset announced via ProteomeXchange.

Title	A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes
Description	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.
HostingRepository	PRIDE
AnnounceDate	2018-10-22
AnnouncementXML	Submission_2018-10-22_11:04:24.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chiaowen Hsiao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-19 01:24:31	ID requested
⏵ 1	2018-10-22 11:04:26	announced

Engelmann BW, Hsiao CJ, Blischak JD, Fourne Y, Khan Z, Ford M, Gilad Y, A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes. Sci Rep, 8(1):12106(2018) [pubmed]

curator keyword: Biological

submitter keyword: Human, YRI, LCL, LC-MS/MS, MaxQuant

Yoav Gilad
contact affiliation	Department of Human Genetics, University of Chicago, Chicago, Illinois, USA; Department of Medicine, University of Chicago, Chicago, Illinois, USA
contact email	gilad@uchicago.edu
lab head
Chiaowen Hsiao
contact affiliation	University of Chicago
contact email	joycehsiao@uchicago.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008002
     1. Label: PRIDE project
     2. Name: A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes