Comprehensive Cell Type Decomposition of Circulating Cell-free DNA with CelFiE

Overview

Journal Nat Commun

Specialty Biology

Date 2021 May 12

PMID 33976150

Citations 24

Authors

Christa Caggiano

Barbara Celona

Fleur Garton

Joel Mefford

Brian L Black

Robert Henderson

Catherine Lomen-Hoerth

Andrew Dahl

Noah Zaitlen

Affiliations

Soon will be listed here.

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.

Citing Articles

Whole-genome bisulfite sequencing of cell-free DNA unveils age-dependent and ALS-associated methylation alterations.

Jin Y, Conneely K, Ma W, Naviaux R, Siddique T, Allen E Cell Biosci. 2025; 15(1):26.

PMID: 39980027 PMC: 11843967. DOI: 10.1186/s13578-025-01366-1.

Circulating Cell-Free DNA in Metabolic Diseases.

Pollastri A, Kovacs P, Keller M J Endocr Soc. 2025; 9(2):bvaf006.

PMID: 39850787 PMC: 11756337. DOI: 10.1210/jendso/bvaf006.

Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.

Harvey C, Nowak A, Zhang S, Moll T, Weimer A, Barcons A BMC Med Genomics. 2025; 18(1):10.

PMID: 39810183 PMC: 11734586. DOI: 10.1186/s12920-025-02084-w.

Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans.

Rodrigues K, Weng Z, Graham Z, Lavin K, McAdam J, Tuggle S Proc Natl Acad Sci U S A. 2025; 122(3):e2406954122.

PMID: 39805013 PMC: 11761974. DOI: 10.1073/pnas.2406954122.

Systematic evaluation of methylation-based cell type deconvolution methods for plasma cell-free DNA.

Sun T, Yuan J, Zhu Y, Li J, Yang S, Zhou J Genome Biol. 2024; 25(1):318.

PMID: 39702273 PMC: 11660681. DOI: 10.1186/s13059-024-03456-8.

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