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Updated: Jun 15, 2025
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Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
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MetDecode: methylation-based deconvolution of cell-free DNA for noninvasive multi-cancer typing.
Antoine Passemiers1, Stefania Tuveri2, Dhanya Sudhakaran2
1Dynamical Systems, Signal Processing and Data Analytics (STADIUS), Department of Electrical Engineering, KU Leuven, Leuven, 3001, Belgium.
Bioinformatics (Oxford, England)
|August 23, 2024
Summary
MetDecode accurately identifies cancer tissue of origin from cell-free DNA (cfDNA) using DNA methylation. This noninvasive method aids in cancer diagnosis and characterization by analyzing cfDNA alterations.
Area of Science:
- Genomics
- Biomarker Discovery
- Computational Biology
Background:
- Circulating-cell free DNA (cfDNA) is a promising noninvasive biomarker for cancer detection.
- Identifying the tissue of origin for cfDNA is crucial for understanding cancer biology and guiding treatment.
Purpose of the Study:
- To develop and validate a computational algorithm for identifying the tissue of origin of cfDNA.
- To assess the performance of the algorithm in silico and in patient samples.
Main Methods:
- Developed MetDecode, a DNA methylation signature-based deconvolution algorithm.
- Created a reference methylation atlas using whole-genome sequencing data from various cancers and blood cells.
- Incorporated on-the-fly learning for absent contributors and accounted for marker region coverage.
Main Results:
- In silico experiments demonstrated a detection limit of 2.88% tumor contribution in cfDNA.
- MetDecode achieved high accuracy (Pearson correlation > 0.95) and outperformed other methods in simulations.
- Correctly assigned tissue-of-origin in 84.2% of plasma cfDNA samples from cancer patients.
Conclusions:
- MetDecode accurately estimates the contribution of multiple tissues in cfDNA.
- The algorithm provides valuable biological insights for cancer characterization and clinical management.
- MetDecode is a robust tool for analyzing cfDNA alterations, even with an imperfect reference atlas.
