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CelFiE: Comprehensive cell type decomposition of circulating cell-free DNA

ABSTRACT: CelFiE: Comprehensive cell type decomposition of circulating cell-free DNA

PROVIDER: PRJNA691320 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13404367_1.fastq.gz	Fastqsanger.gz
	SRR13404367_2.fastq.gz	Fastqsanger.gz
	SRR13404368_1.fastq.gz	Fastqsanger.gz
	SRR13404368_2.fastq.gz	Fastqsanger.gz
	SRR13404369_1.fastq.gz	Fastqsanger.gz

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CelFiE: Comprehensive cell type decomposition of circulating cell-free DNA

Project description:Circulating cell-free DNA (cfDNA) in the bloodstream originates from dying cells and is a promising non-invasive biomarker for cell death. Here, we propose an algorithm, CelFiE, to accurately estimate relative abundances of cell types and tissues contributing to cfDNA from epigenetic cfDNA sequencing. In contrast to previous work, CelFiE accommodates low coverage data, does not rely on CpG site curation, and estimates contributions from multiple unknown cell types that are not available in external reference data. In simulations, CelFiE accurately estimates known and unknown cell type proportions from low coverage and noisy cfDNA mixtures, including from rare cell types composing less than 1% of the total mixture. In a positive control of cfDNA extracted from pregnant and non-pregnant women, CelFiE correctly estimates a large placenta component specifically in pregnant women (p = 4.5x10^-5). In cfDNA from ALS patients and age-matched controls, we observed increased cfDNA concentrations in ALS patients (p = 5.0x10^-3), and CelFiE identified a corresponding increased skeletal muscle component (p = 2.4x10^-3), consistent with muscle impairment characterizing ALS. Together these results show CelFiE may be a useful tool for biomarker discovery and monitoring of degenerative disease progression.

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