Measuring single cell divisions in human tissues from multi-region sequencing data.
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Date
2020-02-25ICR Author
Author
Werner, B
Case, J
Williams, MJ
Chkhaidze, K
Temko, D
Fernández-Mateos, J
Cresswell, GD
Nichol, D
Cross, W
Spiteri, I
Huang, W
Tomlinson, IPM
Barnes, CP
Graham, TA
Sottoriva, A
Type
Journal Article
Metadata
Show full item recordAbstract
Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in humans remains challenging. Here, we show that multi-sample genomic data from a single time point of normal and cancer tissues contains information on single-cell divisions. We present a new theoretical framework that, applied to whole-genome sequencing data of healthy tissue and cancer, allows inferring the mutation rate and the cell survival/death rate per division. On average, we found that cells accumulate 1.14 mutations per cell division in healthy haematopoiesis and 1.37 mutations per division in brain development. In both tissues, cell survival was maximal during early development. Analysis of 131 biopsies from 16 tumours showed 4 to 100 times increased mutation rates compared to healthy development and substantial inter-patient variation of cell survival/death rates.
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Subject
Brain
Neurons
Humans
Neoplasms
Bayes Theorem
Reproducibility of Results
Cell Division
Hematopoiesis
Cell Survival
Genetic Heterogeneity
Models, Genetic
Single-Cell Analysis
Mutation Rate
Mutation Accumulation
Whole Genome Sequencing
Research team
Evolutionary Genomics & Modelling
Language
eng
Date accepted
2020-01-29
License start date
2020-02-25
Citation
Nature communications, 2020, 11 (1), pp. 1035 - ?
Publisher
NATURE PUBLISHING GROUP