Bayesian analysis of normal mouse cell lineage trees allowing intra-individual, cell population specific mutation rates

Abstract

Individual cell lineage trees are of biological and clinical importance. The Sanger Mouse Pilot Study used clonal organoid lines of endodermal origin to extract somatic base substitutions from single cells of two healthy mice. Here we applied Bayesian phylogenetics analysis using the Pilots 35 somatic base substitutions in order to reconstruct the two cell trees and apply relaxed clock methods allowing intra-individual, cell lineage specific mutation rates. Detailed analysis provided support for the strict clock for mouse_1 and relaxed clock for mouse_2. Interestingly, a clade of two prostate organoid lines in mouse_2 presented one outlier branch mutation rate compared to the mean rates calculated. Based on this study unbiased clock analysis has the potential to add a new, useful layer to our understanding of normal and disturbed cell lineage trees. This study is the first to apply the popular Bayesian BEAST package to individual single cell resolution data.