This repository contains the code and necessary files to accompany the manuscript "Mutation rates and fitness consequences of mosaic chromosomal alterations in blood". Code was written using Python.

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The mCA calls used in our analysis, generated by Loh et al are available from UK Biobank (Return 3094), via an application process. Autosomal mCA calls, in anonymized form, can be found in 'Supplementary_data_annotated_cw.csv.zip' and can also be obtained from Loh, P-R., Genovese G. & McCarroll S. Monogenic and polygenic inheritance become instruments for clonal selection, Supplementary Data: https://doi.org/10.1038/s41586-020-2430-6 (2020).

Code & data for generation of figures/ analyses in main text:

Figure 1 (Estimating mCA mutation rates and fitness effects):

• Github folder: Maximum likelihood parameter estimation for autosomal mCAs/Estimating mCA mutation rates and fitness effects.ipynb

Figure 2 (The fitness and mutational landscape of autosomal mCAs):

• Figure 2a:
  • Github folder: Maximum likelihood parameter estimation for autosomal mCAs
• Figure 2b:
  • Github folder: Maximum likelihood parameter estimation for autosomal mCAs/DFEs (mCAs) and DFE of SNVs vs mCAs.ipynb
• Figure 2c:
  • Github folder: Sex differences in mCA fitness effects and mutation rates

Figure 3 (Age dependence of mCAs):

• Github folder: Age dependence of mCAs

Figure 4 (mCA fitness effects and blood cancer risk):

• Github folder: Blood cancer risk

Figure 5 (mLOY and mLOX):

• Github folder: mLOY and mLOX

Figure 6 (Distribution of fitness effects (DFE) for mCAs vs SNVs):

• Github folder: Maximum likelihood parameter estimation for autosomal mCAs/DFEs (mCAs) and DFE of SNVs vs mCAs.ipynb

Code & data for generation of Extended Data figures:

Extended Data Figures 1-7 (Parameter estimation for individual mCAs):

• Github folder: Maximum likelihood parameter estimation for autosomal mCAs

Extended Data Figure 8 (Parameter estimation for mLOY and mLOX):

• Github folder: mLOY and mLOX

Extended Data Figure 9 (Simulated mLOX calls with 2 different mutation rates and fitness effects):

• Github folder: Simulated data

Extended Data Figure 10 (mLOX detected among ∼260,000 female UK Biobank participants):

• Github folder: mLOY and mLOX

Code & data for generation of figures/ analyses in supplement:

Supplementary Figures 1-2 (mCAs detected among ~500,000 UK Biobank participants):

• Github folder: Overview of data used in analysis

Supplementary Figure 3 (Number of observations of each mCA):

• Github folder: Overview of data used in analysis

Supplementary Figure 4 (Number of autosomal mCAs per person):

• Github folder: Overview of data used in analysis

Supplementary Figures 5-6 (Effect of upper and lower mCA detection limits on fitness and mutation rate inferences):

• Github folder: Simulated data

Supplementary Figure 7 (Effect of false negatives at low cell fraction):

• Github folder: Maximum likelihood parameter estimation for autosomal mCAs

Supplementary Figures 8-14 (Sex differences in fitness effects and mutation rates):

• Github folder: Sex differences in mCA fitness effects and mutation rates

Supplementary Figures 15-17 (Age and sex dependence of individual mCAs):

• Github folder: Age dependence of mCAs

Supplementary Figures 18-22 (Deviation from expected age dependence):

• Github folder: Age dependence of mCAs

Supplementary Figure 23 (Age dependence of clone size distributions):

• Github folder: Age dependence of mCAs

Supplementary Figure 24 (Single vs. multiple mCA events):

• Github folder: Maximum likelihood parameter estimation for autosomal mCAs

Supplementary Figure 25 (Length dependence of fitness and mutation rates):

• Github folder: Length dependence of mCAs

Supplementary Figure 26 (Relationship with more descriptive metrics):

• Github folder: Maximum likelihood parameter estimation for autosomal mCAs

Supplementary Figure 27 (High mutation rate events):

• Github folder: Simulated data

LICENSE

GNU General Public License v3.0