Population-scale proteome variation in human induced pluripotent stem cells
Type
ArticleAuthors
Mirauta, Bogdan Andrei
Seaton, Daniel D.
Bensaddek, Dalila
Brenes, Alejandro
Bonder, Marc Jan

Kilpinen, Helena

Agu, Chukwuma A.
Alderton, Alex
Danecek, Petr
Denton, Rachel
Durbin, Richard
Gaffney, Daniel J.
Goncalves, Angela
Halai, Reena
Harper, Sarah
Kirton, Christopher M.
Kolb-Kokocinski, Anja
Leha, Andreas
McCarthy, Shane A.
Memari, Yasin
Patel, Minal
Birney, Ewan
Paolo Casale, Francesco
Clarke, Laura
Harrison, Peter W.
Streeter, Ian
Denovi, Davide
Meleckyte, Ruta
Moens, Natalie
Watt, Fiona M.
Ouwehand, Willem H.
Beales, Philip
Stegle, Oliver

Lamond, Angus I.

KAUST Department
Proteomics and Protein ExpressionDate
2020-08-10Submitted Date
2020-03-30Permanent link to this record
http://hdl.handle.net/10754/665584
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Human disease phenotypes are driven primarily by alterations in protein expression and/or function. To date, relatively little is known about the variability of the human proteome in populations and how this relates to variability in mRNA expression and to disease loci. Here, we present the first comprehensive proteomic analysis of human induced pluripotent stem cells (iPSC), a key cell type for disease modelling, analysing 202 iPSC lines derived from 151 donors, with integrated transcriptome and genomic sequence data from the same lines. We characterised the major genetic and non-genetic determinants of proteome variation across iPSC lines and assessed key regulatory mechanisms affecting variation in protein abundance. We identified 654 protein quantitative trait loci (pQTLs) in iPSCs, including disease-linked variants in protein-coding sequences and variants with trans regulatory effects. These include pQTL linked to GWAS variants that cannot be detected at the mRNA level, highlighting the utility of dissecting pQTL at peptide level resolution.Citation
Mirauta, B. A., Seaton, D. D., Bensaddek, D., Brenes, A., Bonder, M. J., … Kilpinen, H. (2020). Population-scale proteome variation in human induced pluripotent stem cells. eLife, 9. doi:10.7554/elife.57390Publisher
eLife Sciences Publications, LtdJournal
eLifeAdditional Links
https://elifesciences.org/articles/57390ae974a485f413a2113503eed53cd6c53
10.7554/ELIFE.57390
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