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Impact of regulatory variation across human iPSCs and differentiated cells [ATAC-seq iPSC]

ABSTRACT: Impact of regulatory variation across human iPSCs and differentiated cells [ATAC-seq iPSC]

PROVIDER: PRJNA427323 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6412410_1.fastq.gz	Fastqsanger.gz
	SRR6412410_2.fastq.gz	Fastqsanger.gz
	SRR6412420_1.fastq.gz	Fastqsanger.gz
	SRR6412420_2.fastq.gz	Fastqsanger.gz
	SRR6412430_1.fastq.gz	Fastqsanger.gz

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Project description:Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. Here we investigate the use of iPSCs and iPSC-derived cells to study the impact of genetic variation across different cell types and as models for the genetics of complex disease. We established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring RNA, chromatin accessibility and DNA methylation. Regulatory variation between individuals is lower in iPSCs than in the differentiated cell types, consistent with the intuition that developmental processes are generally canalized. While most cell-type- specific regulatory effects lie in chromatin that is open only in the affected cell-types, we find that 20% of cell-type specific effects are in shared open chromatin. Finally, we developed deep neural network models to predict open chromatin regions in these cell types from DNA sequence alone and were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on tissue-specific chromatin accessibility. Our results provide a framework for using iPSC technology to study regulatory variation in cell types that are otherwise inaccessible. Keywords: Expression profiling by high throughput sequencing

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