Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization.
Nat Commun
; 14(1): 6042, 2023 09 27.
Article
in En
| MEDLINE
| ID: mdl-37758728
ABSTRACT
Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection. We apply this method to plasma samples of 497 healthy controls and 780 patients of seven cancer types and develop an ensemble classifier by incorporating methylation, fragmentation, and CNA features. In the test cohort, our approach achieves an area under the curve value of 0.966 for overall cancer detection. Detection sensitivity for early-stage patients achieves 73% at 99% specificity. Finally, we demonstrate the feasibility to accurately localize the origin of cancer signals with combined methylation and fragmentation profiling of tissue-specific accessible chromatin regions. Overall, this proof-of-concept study provides a technical platform to utilize multimodal cfDNA features for improved cancer detection.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell-Free Nucleic Acids
/
Neoplasms
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2023
Document type:
Article
Affiliation country:
China