Feb 4, 2014

Inferring clonal evolution of tumors from single nucleotide somatic mutations

BMC Bioinformatics
Wei JiaoQuaid Morris

Abstract

High-throughput sequencing allows the detection and quantification of frequencies of somatic single nucleotide variants (SNV) in heterogeneous tumor cell populations. In some cases, the evolutionary history and population frequency of the subclonal lineages of tumor cells present in the sample can be reconstructed from these SNV frequency measurements. But automated methods to do this reconstruction are not available and the conditions under which reconstruction is possible have not been described. We describe the conditions under which the evolutionary history can be uniquely reconstructed from SNV frequencies from single or multiple samples from the tumor population and we introduce a new statistical model, PhyloSub, that infers the phylogeny and genotype of the major subclonal lineages represented in the population of cancer cells. It uses a Bayesian nonparametric prior over trees that groups SNVs into major subclonal lineages and automatically estimates the number of lineages and their ancestry. We sample from the joint posterior distribution over trees to identify evolutionary histories and cell population frequencies that have the highest probability of generating the observed SNV frequency data. When multiple phylogenies...Continue Reading

  • References18
  • Citations64

References

  • References18
  • Citations64

Mentioned in this Paper

DOCK9 gene
Tumor Cells, Uncertain Whether Benign or Malignant
CXorf36 gene
Anatomical Layer
Tumor Tissue Sample
Cytological Techniques
Somatic Mutation
Neoplastic Cell
Neoplasms
Acute Myeloid Leukemia Pathway

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