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Chunk #9 — Introduction — Sources of iPSC heterogeneity

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Common genetic variation drives molecular heterogeneity in human iPSCs.
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Characterisation of multiple lines per donor enabled us to quantify the variance contributed by between-individual differences (hereafter, ‘donor effects’) and systematically compare this with variance from other factors, substantially extending previous analyses in smaller cohorts6,7 (Fig. 3a-c). We identified consistent donor effects for most measured iPSC phenotypes, ranging from DNA methylation, through mRNA and protein abundance to pluripotency, differentiation, and cell morphology (Fig. 3b,c). After accounting for assay-specific batch factors (full list in Methods), donor effects explained 5.2-26.3% of the variance in the genome-wide assays (Fig. 3a), 21.4-45.8% in protein immunostaining (Fig. 3b), and 7.8-22.8% in cellular morphology (Fig. 3c). Collectively, these results indicate that differences between donor individuals affect most iPSC cellular traits.