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 journalArticleAcademicpeer-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
Article numbere0208002
JournalPLoS ONE
Volume13
Issue number11
DOIs
Publication statusPublished - 2018

Cite this

Nieboer, M. M., Dorssers, L. C. J., Straver, R., Looijenga, L. H. J., & de Ridder, J. (2018). Targetclone: A multi-sample approach for reconstructing subclonal evolution of tumors. PLoS ONE, 13(11), [e0208002]. https://doi.org/10.1371/journal.pone.0208002
Nieboer, Marleen M. ; Dorssers, Lambert C. J. ; Straver, Roy ; Looijenga, Leendert H. J. ; de Ridder, Jeroen. / Targetclone: A multi-sample approach for reconstructing subclonal evolution of tumors. In: PLoS ONE. 2018 ; Vol. 13, No. 11.
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Nieboer, MM, Dorssers, LCJ, Straver, R, Looijenga, LHJ & de Ridder, J 2018, 'Targetclone: A multi-sample approach for reconstructing subclonal evolution of tumors' PLoS ONE, vol. 13, no. 11, e0208002. https://doi.org/10.1371/journal.pone.0208002

Targetclone: A multi-sample approach for reconstructing subclonal evolution of tumors. / Nieboer, Marleen M.; Dorssers, Lambert C. J.; Straver, Roy; Looijenga, Leendert H. J.; de Ridder, Jeroen.

In: PLoS ONE, Vol. 13, No. 11, e0208002, 2018.

Research output: Contribution to journalArticleAcademicpeer-review

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Nieboer MM, Dorssers LCJ, Straver R, Looijenga LHJ, de Ridder J. Targetclone: A multi-sample approach for reconstructing subclonal evolution of tumors. PLoS ONE. 2018;13(11). e0208002. https://doi.org/10.1371/journal.pone.0208002