Abstract
SummaryTumour evolution results in progressive cancer phenotypes such as metastatic spread and treatment resistance. To better treat cancers, we must characterize tumour evolution and the genetic events that confer progressive phenotypes. This is facilitated by high coverage genome or exome sequencing. However, the best approach by which, or indeed whether, these data can be used to accurately model and interpret underlying evolutionary dynamics is yet to be confirmed. Establishing this requires sequencing data from appropriately heterogeneous tumours in which the exact trajectory and combination of events occurring throughout its evolution are known. We therefore developed HeteroGenesis: a tool to generate realistically evolved tumour genomes, which can be sequenced using weighted-Wessim (w-Wessim), an in silico exome sequencing tool that we have adapted from previous methods. HeteroGenesis simulates more complex and realistic heterogeneous tumour genomes than existing methods, can model different evolutionary dynamics, and enables the creation of multi-region and longitudinal data.Availability and implementationHeteroGenesis and w-Wessim are freely available under the GNU General Public Licence from https://github.com/GeorgetteTanner, implemented in Python and supported on linux and MS Windows.Supplementary information Supplementary data are available at Bioinformatics online.
Highlights
The evolution of a tumour affects its clinical course: malignant phenotypes undergo selection resulting in increased growth, invasion, metastases or therapy resistance
HeteroGenesis: a clonal tumour genome simulator evolution, such as: (i) multi-level subclone phylogenies, (ii) individual chromosome and whole-genome aneuploidy, (iii) overlapping copy number variants (CNVs)— either nested within the same chromosome copy, or partially or fully overlapping the same region on different copies, (iv) variants occurring in a flexible order and (v) distinct germline and somatic variants
We developed HeteroGenesis: a simulator of genomes from realistically heterogeneous tumours that can result from varied and user-determined evolutionary trajectories
Summary
The evolution of a tumour affects its clinical course: malignant phenotypes undergo selection resulting in increased growth, invasion, metastases or therapy resistance. HeteroGenesis: a clonal tumour genome simulator evolution, such as: (i) multi-level subclone phylogenies, (ii) individual chromosome and whole-genome aneuploidy, (iii) overlapping copy number variants (CNVs)— either nested within the same chromosome copy, or partially or fully overlapping the same region on different copies, (iv) variants occurring in a flexible order and (v) distinct germline and somatic variants (see Supplementary Table S1). To address these shortcomings, we developed HeteroGenesis: a simulator of genomes from realistically heterogeneous tumours that can result from varied and user-determined evolutionary trajectories. These tools create sequencing data and ‘ground truth’ variant profiles for simulated bulk tumour samples, which can include ‘normal’ contamination and be manipulated to model multi-region and longitudinal sampling
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