Population-scale proteome variation in human induced pluripotent stem cells

Bogdan Andrei Mirauta, Daniel D. Seaton, Dalila Bensaddek, Alejandro Brenes, Marc Jan Bonder, Helena Kilpinen, Chukwuma A. Agu, Alex Alderton, Petr Danecek, Rachel Denton, Richard Durbin, Daniel J. Gaffney, Angela Goncalves, Reena Halai, Sarah Harper, Christopher M. Kirton, Anja Kolb-Kokocinski, Andreas Leha, Shane A. McCarthy, Yasin MemariMinal Patel, Ewan Birney, Francesco Paolo Casale, Laura Clarke, Peter W. Harrison, Ian Streeter, Davide Denovi, Ruta Meleckyte, Natalie Moens, Fiona M. Watt, Willem H. Ouwehand, Philip Beales, Oliver Stegle, Angus I. Lamond

    Research output: Contribution to journalArticlepeer-review

    32 Scopus citations


    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.
    Original languageEnglish (US)
    Pages (from-to)1-22
    Number of pages22
    StatePublished - Aug 10 2020

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    KAUST Repository Item: Exported on 2020-10-16


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