Journal Article

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

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

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Algorithms / Alleles / Analysis / Bioinformatics / Biology / Biology and Life Sciences / Cancer / Clonal Evolution - genetics / Colorectal cancer / Computational Biology - methods / Computer and Information Sciences / Computer applications / Computer simulation / Depth measurement / DNA Copy Number Variations - genetics / DNA methylation / Evolution / Gene frequency / Gene Frequency - genetics / Genetic polymorphisms / Genomes / Health aspects / Heterogeneity / Heterogeneous catalysis / High-Throughput Nucleotide Sequencing - methods / Humans / Medical research / Medicine / Medicine and Health Sciences / Methods / Mutation / Mutation - genetics / Neoplasms - genetics / Novels / Oncology / Ovarian cancer / Ovarian carcinoma / Physical Sciences / Polymorphism / Polymorphism, Single Nucleotide - genetics / Research and Analysis Methods / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Software / Trees / Tumors