Repository logo
 

Population-scale proteome variation in human induced pluripotent stem cells.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Mirauta, Bogdan Andrei  ORCID logo  https://orcid.org/0000-0002-9733-292X
Seaton, Daniel D 
Bensaddek, Dalila 
Brenes, Alejandro 

Abstract

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.

Description

Keywords

deleterious variants, genetics, genomics, human, induced pluripotent stem cells, proteomics, Adolescent, Adult, Aged, Child, Child, Preschool, Disease, Female, Genetic Variation, Genetics, Population, Genotype, Humans, Induced Pluripotent Stem Cells, Infant, Infant, Newborn, Male, Middle Aged, Phenotype, Proteome, Proteomics, Quantitative Trait Loci, RNA, Messenger, Transcriptome, Young Adult

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

9

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Medical Research Council (MR/L016311/1)
Wellcome Trust (098503/B/12/Z)