A Clonal Evolution Simulator for Planning Somatic Evolution Studies

Abstract

Somatic evolution plays a key role in development, cell differentiation, and normal aging, but also diseases such as cancer. Understanding mechanisms of somatic mutability and how they can vary between cell lineages will likely play a crucial role in biological discovery and medical applications. This need has led to a proliferation of new technologies for profiling single-cell variation, each with distinctive capabilities and limitations that can be leveraged alone or in combination with other technologies. The enormous space of options for assaying somatic variation, however, presents unsolved informatics problems with regards to selecting optimal combinations of technologies for designing appropriate studies for any particular scientific questions. Versatile simulation tools are needed to explore and optimize potential study designs if researchers are to deploy multiomic technologies most effectively. In this paper, we present a simulator allowing for the generation of synthetic data from a wide range of clonal lineages, variant classes, and sequencing technology choices, intended to provide a platform for effective study design in somatic lineage analysis. Users can input various properties of the somatic evolutionary system, mutation classes, and biotechnology options and then generate samples of synthetic sequence reads and their corresponding ground-truth parameters for a given study design. We demonstrate the utility of the simulator for testing and optimizing study designs for various experimental queries.