Submitted by ja607 on
Title | Comprehensive cell type decomposition of circulating cell-free DNA with CelFiE. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Caggiano, C, Celona, B, Garton, F, Mefford, J, Black, BL, Henderson, R, Lomen-Hoerth, C, Dahl, A, Zaitlen, N |
Journal | Nat Commun |
Volume | 12 |
Issue | 1 |
Pagination | 2717 |
Date Published | 2021 05 11 |
ISSN | 2041-1723 |
Keywords | Adult, 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 |
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. |
DOI | 10.1038/s41467-021-22901-x |
Alternate Journal | Nat Commun |
PubMed ID | 33976150 |
PubMed Central ID | PMC8113516 |
Grant List | P01 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 |