Population-scale proteome variation in human induced pluripotent stem cells.
Elife
; 92020 08 10.
Article
em En
| MEDLINE
| ID: mdl-32773033
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Doença
/
Proteoma
/
Células-Tronco Pluripotentes Induzidas
/
Transcriptoma
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article