The long-term effects of chemotherapy on normal blood cells

Data to accompany manuscript: The long-term effects of chemotherapy on normal blood cells

Abstract
In developed countries, up to 10% of individuals may be exposed to systemic chemotherapy for cancer and other diseases. Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage to normal tissues. To investigate the impact of chemotherapy on mutation burdens and cell population structure of a normal tissue we sequenced blood cell genomes from 23 individuals, aged 3–80 years, treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but there were differences in burden between different classes of agent, different agents of the same class and different blood cell types. Chemotherapy also induced premature changes in the cell population structure of normal blood, similar to those of normal ageing. The results constitute an initial survey of the long-term biological consequences of cytotoxic agents to which a substantial fraction of the population is exposed during the course of their disease management, raising mechanistic questions and highlighting opportunities for mitigation of adverse effects.

Datasets provided here:
1) Small datasets per individual (32 individuals, one sampled at two time points)

a) Annotated_mutation_files: XXXX_annotated_muts.csv
SBS and indel mutation calls with tree node assignments (column node) and gene / mutation type annotation.

b) Tree_files: XXXX.tree
The raw tree with branch lengths equal to number of mutations assigned (without adjustment for sequencing coverage).

2) Large datasets per individual (5 normal and 5 chemotherapy exposed)
a) annotated_mut_set_XXXX_01_standard_rho01
This is an R data object and is uploaded into an R workspace using load()
The genotype matrix used for MPBoot tree building is available in the matrix: filtered_muts$Genotype_shared_bin
The dna strings used as input for MPboot are available in the vector: filtered_muts$dna_strings
The annotated variant calls with tree node information are available in the matrix: filtered_muts$COMB_mats.tree.build$mat
The genotype matrix of mutations calls per sample is available in: filtered_muts$COMB_mats.tree.build$Genotype_bin
Information on whether the variant is an SNV or indel is available in: filtered_muts$COMB_mats.tree.build$mat$Mut_type
A summary of total numbers of shared and private SNVs and indels is available in:
filtered_muts$summary

b) XXXX_sensitivity
This file contains information on the sensitivity of SNV and Indel calls per sample.

c) tree_XXXX_01_standard_rho01.tree
The raw tree with branch lengths equal to number of mutations assigned (without adjustment for sequencing coverage).

3) Nanoseq dataset