Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology.
Nat Commun
; 15(1): 2220, 2024 Mar 12.
Article
em En
| MEDLINE
| ID: mdl-38472221
ABSTRACT
Circulating cell-free DNA (cfDNA) fragments have characteristics that are specific to the cell types that release them. Current methods for cfDNA deconvolution typically use disease tailored marker selection in a limited number of bulk tissues or cell lines. Here, we utilize single cell transcriptome data as a comprehensive cellular reference set for disease-agnostic cfDNA cell-of-origin analysis. We correlate cfDNA-inferred nucleosome spacing with gene expression to rank the relative contribution of over 490 cell types to plasma cfDNA. In 744 healthy individuals and patients, we uncover cell type signatures in support of emerging disease paradigms in oncology and prenatal care. We train predictive models that can differentiate patients with colorectal cancer (84.7%), early-stage breast cancer (90.1%), multiple myeloma (AUC 95.0%), and preeclampsia (88.3%) from matched controls. Importantly, our approach performs well in ultra-low coverage cfDNA datasets and can be readily transferred to diverse clinical settings for the expansion of liquid biopsy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácidos Nucleicos Livres
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article