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

TitleComprehensive cell type decomposition of circulating cell-free DNA with CelFiE.
Publication TypeJournal Article
Year of Publication2021
AuthorsCaggiano, C, Celona, B, Garton, F, Mefford, J, Black, BL, Henderson, R, Lomen-Hoerth, C, Dahl, A, Zaitlen, N
JournalNat Commun
Date Published2021 05 11
KeywordsAdult, Algorithms, Amyotrophic Lateral Sclerosis, B-Lymphocytes, Biomarkers, Case-Control Studies, Cell-Free Nucleic Acids, DNA Methylation, Epigenesis, Genetic, Female, Humans, Macrophages, Male, Monocytes, Muscle, Skeletal, Neutrophils, Organ Specificity, Pregnancy, Pregnancy Trimesters, T-Lymphocytes

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.

Alternate JournalNat Commun
PubMed ID33976150
PubMed Central IDPMC8113516
Grant ListP01 HL146366 / HL / NHLBI NIH HHS / United States
R01 ES029929 / ES / NIEHS NIH HHS / United States
K25 HL121295 / HL / NHLBI NIH HHS / United States
R03 DE025665 / DE / NIDCR NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
R01 HL064658 / HL / NHLBI NIH HHS / United States
T32 NS048004 / NS / NINDS NIH HHS / United States
R01 CA227237 / CA / NCI NIH HHS / United States