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

Christa Caggiano, Barbara Celona, Fleur Garton, Joel Mefford, Brian L. Black, Robert Henderson, Catherine Lomen-Hoerth, Andrew Dahl and Noah Zaitlen ()
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Christa Caggiano: University of California Los Angeles
Barbara Celona: University of California San Francisco
Fleur Garton: University of Queensland
Joel Mefford: University of California Los Angeles
Brian L. Black: University of California San Francisco
Robert Henderson: Royal Brisbane and Women’s Hospital
Catherine Lomen-Hoerth: University of California San Francisco
Andrew Dahl: University of Chicago
Noah Zaitlen: University of California Los Angeles

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Circulating cell-free DNA (cfDNA) in the bloodstream originates from dying cells and is a promising noninvasive biomarker for cell death. Here, we propose an algorithm, CelFiE, to accurately estimate the 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 require 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 cell types composing less than 1% of the total mixture. When used in two clinically-relevant situations, CelFiE correctly estimates a large placenta component in pregnant women, and an elevated skeletal muscle component in amyotrophic lateral sclerosis (ALS) patients, consistent with the occurrence of muscle wasting typical in these patients. Together, these results show how CelFiE could be a useful tool for biomarker discovery and monitoring the progression of degenerative disease.

Date: 2021
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DOI: 10.1038/s41467-021-22901-x

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