TargetClone: A multi-sample approach for reconstructing subclonal evolution of tumors

Marleen M Nieboer, Lambert C J Dorssers, Roy Straver, Leendert H J Looijenga, Jeroen de Ridder

Research output: Contribution to journalArticlepeer-review

Abstract

Most tumors are composed of a heterogeneous population of subclones. A more detailed insight into the subclonal evolution of these tumors can be helpful to study progression and treatment response. Problematically, tumor samples are typically very heterogeneous, making deconvolving individual tumor subclones a major challenge. To overcome this limitation, reducing heterogeneity, such as by means of microdissections, coupled with targeted sequencing, is a viable approach. However, computational methods that enable reconstruction of the evolutionary relationships require unbiased read depth measurements, which are commonly challenging to obtain in this setting. We introduce TargetClone, a novel method to reconstruct the subclonal evolution tree of tumors from single-nucleotide polymorphism allele frequency and somatic single-nucleotide variant measurements. Furthermore, our method infers copy numbers, alleles and the fraction of the tumor component in each sample. TargetClone was specifically designed for targeted sequencing data obtained from microdissected samples. We demonstrate that our method obtains low error rates on simulated data. Additionally, we show that our method is able to reconstruct expected trees in a testicular germ cell cancer and ovarian cancer dataset. The TargetClone package including tree visualization is written in Python and is publicly available at https://github.com/UMCUGenetics/targetclone.

Original languageEnglish
Pages (from-to)e0208002
JournalPloS one
Volume13
Issue number11
DOIs
Publication statusPublished - 2018

Keywords

  • Algorithms
  • Alleles
  • Clonal Evolution/genetics
  • Computational Biology/methods
  • DNA Copy Number Variations/genetics
  • Gene Frequency/genetics
  • High-Throughput Nucleotide Sequencing/methods
  • Humans
  • Mutation/genetics
  • Neoplasms/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Software

Fingerprint

Dive into the research topics of 'TargetClone: A multi-sample approach for reconstructing subclonal evolution of tumors'. Together they form a unique fingerprint.

Cite this