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Population-scale proteome variation in human induced pluripotent stem cells
- Source :
- eLife, eLife, Vol 9 (2020)
- Publication Year :
- 2020
- Publisher :
- eLife Sciences Publications, Ltd, 2020.
-
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.
- Subjects :
- Male
Proteomics
Proteome
Genome-wide association study
VARIANTS
Transcriptome
0302 clinical medicine
SCHIZOPHRENIA
Human proteome project
genetics
Disease
Biology (General)
Induced pluripotent stem cell
Child
GENE-EXPRESSION
0303 health sciences
education.field_of_study
Drug discovery
General Neuroscience
General Medicine
Middle Aged
Phenotype
Child, Preschool
Medicine
ABUNDANCE
Female
Research Article
Adult
Adolescent
Genotype
QH301-705.5
induced pluripotent stem cells
Science
Population
Quantitative Trait Loci
deleterious variants
Genomics
Computational biology
Quantitative trait locus
Biology
General Biochemistry, Genetics and Molecular Biology
DIFFERENTIAL EXPRESSION
03 medical and health sciences
Young Adult
RESOURCE
REVEALS
genomics
Humans
human
RNA, Messenger
education
030304 developmental biology
Aged
IDENTIFICATION
General Immunology and Microbiology
Infant, Newborn
Genetic Variation
Infant
Genetics and Genomics
QUANTIFICATION
Genetics, Population
REGULATORY VARIATION
3111 Biomedicine
030217 neurology & neurosurgery
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- eLife, eLife, Vol 9 (2020)
- Accession number :
- edsair.doi.dedup.....c18366cc1922197e4e5932603934bd57