This repository contains scripts and Jupyter notebooks for performing many of the analyses presented in "The dynamics of mitochondrial DNA in human tissues and pedigrees: Strong effects of the germline bottleneck, mother's age, and selection". In particular, this repository focuses on the paper's ontogenetic phylogeny likelihood (OPL) methodology.
The recommended order of analysis is:
-
run_mope.sh--- Run this script (or run the listed commands individually) to install MOPE and generate MCMC samples of genetic drift and mutation rate parameters. -
run_de_novo_probabilities.sh--- Run this script to calculate posterior probabiltiies that each observed heteroplasmic mutation is de novo somewhere on the phylogeny of the sampled tissues.
The remaining scripts require output from steps 1) and/or 2). Step 1) in
particular is a big computational task. Subsamples of the authors' MCMC samples
from Step 1) and 2) are provided in the results/ directory, and thus it is
possible to run the remaining analyses without actually repeating the first two
steps.
-
opl_results.ipynb--- Make plots and get summary statistics of genetic drift and mutation rate parameters inferred in step 1). -
postmutloc.ipynb--- Carry out calculations and make plots related to the above posterior de novo probabilities. -
germline_de_novo_regressions.ipynb--- Perform regressions of number of germline de novo mutations against age. -
persistence.ipynb--- Carry out calculations and make plots related to heteroplasmy persistence in the human population. -
mutation_enrichment.ipynb--- Perform calculations on mutation enrichment in different mtDNA position categories, presented in Table S2.