PHYFUM: Phylogenetic Reconstruction of Normal and Pre-malignant Tissue Evolution Using Fluctuating Methylation
Preprint
Abstract
We present PHYFUM, a novel Bayesian phylogenetic method for methylation data that reconstructs the evolutionary history of stem cells and the glandular structures they reside within in normal tissue. Using simulations, we validated this phylogenetic method and confirmed its accuracy. A re-analysis of 22 patients unveiled early gland divergence in the human gut, in contrast to a much later common ancestor in the endometrium, and yielded strong evidence against gland division by segregation of individual stem cells.Keywords
Funding Information
- Advanced Research Projects Agency for Health (ADAPT 140D042590007)
- Thornton Foundation
- Boehringer Ingelheim
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