ArticlePLoS computational biology2016
Bulk Genotyping of Biopsies Can Create Spurious Evidence for Hetereogeneity in Mutation Content.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- The evolution of metapopulation dynamics and the number of stem cells in intestinal crypts and other tissue structures in multicellular bodies.Evolutionary applications · 2020Review
- Genetic heterogeneity and clonal evolution during metastasis in breast cancer patient-derived tumor xenograft models.Computational and structural biotechnology journal · 2020Article
- On measuring selection in cancer from subclonal mutation frequencies.PLoS computational biology · 2019Article
- Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data.PLoS computational biology · 2019Article
- High-resolution deconstruction of evolution induced by chemotherapy treatments in breast cancer xenografts.Scientific reports · 2018Article
- Evolution of Barrett's esophagus through space and time at single-crypt and whole-biopsy levels.Nature communications · 2018Article
- Modeling the Subclonal Evolution of Cancer Cell Populations.Cancer research · 2018Article
- A system for detecting high impact-low frequency mutations in primary tumors and metastases.Oncogene · 2018Article
- Classifying the evolutionary and ecological features of neoplasms.Nature reviews. Cancer · 2017Review
- Quantification of within-sample genetic heterogeneity from SNP-array data.Scientific reports · 2017Article
- Genomic Instability in Cancer: Teetering on the Limit of Tolerance.Cancer research · 2017Review
- PhyloOncology: Understanding cancer through phylogenetic analysis.Biochimica et biophysica acta. Reviews on cancer · 2017Review
- A population genetics perspective on the determinants of intra-tumor heterogeneity.Biochimica et biophysica acta. Reviews on cancer · 2017Review
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Authors and funding
3 authors.
Funding
Abstract
When multiple samples are taken from the neoplastic tissues of a single patient, it is natural to compare their mutation content. This is often done by bulk genotyping of whole biopsies, but the chance that a mutation will be detected in bulk genotyping depends on its local frequency in the sample. When the underlying mutation count per cell is equal, homogenous biopsies will have more high-frequency mutations, and thus more detectable mutations, than heterogeneous ones. Using simulations, we show that bulk genotyping of data simulated under a neutral model of somatic evolution generates strong spurious evidence for non-neutrality, because the pattern of tissue growth systematically generates differences in biopsy heterogeneity. Any experiment which compares mutation content across bulk-genotyped biopsies may therefore suggest mutation rate or selection intensity variation even when these forces are absent. We discuss computational and experimental approaches for resolving this problem.
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Registered trials
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