SCSIM: Jointly simulating correlated single-cell and bulk next-generation DNA sequencing data

Abstract

Background: Recently, it has become possible to collect next-generation DNA sequencing data sets that are composed of multiple samples from multiple biological units where each of these samples may be from a single cell or bulk tissue. Yet, there does not yet exist a tool for simulating DNA sequencing data from such a nested sampling arrangement with single-cell and bulk samples so that developers of analysis methods can assess accuracy and precision. Results: We have developed a tool that simulates DNA sequencing data from hierarchically grouped (correlated) samples where each sample is designated bulk or single-cell. Our tool uses a simple configuration file to define the experimental arrangement and can be integrated into software pipelines for testing of variant callers or other genomic tools. Conclusions: The DNA sequencing data generated by our simulator is representative of real data and integrates seamlessly with standard downstream analysis tools.

CNAsim: improved simulation of single-cell copy number profiles and DNA-seq data from tumors

“…In recent years, a number of simulators have been developed to address this challenge by modeling specific aspects of the scDNA-seq pipeline. These include PSiTE ( Yang et al 2019 ), SCSsim ( Yu et al 2020 ), SCSIM ( Giguere et al 2020 ), MosaicSim ( Srivatsa et al 2022 ), SCSilicon ( Feng and Chen 2022 ), and SimSCSnTree ( Mallory and Nakhleh 2022 ). Among these, SCSIM ( Giguere et al 2020 ) and SCSsim ( Yu et al , 2020 ) generate single-cell sequencing reads assuming biases from the whole-genome amplification (WGA) process, however neither approach models the evolutionary relationships between cells or subclones.…”

“…These include PSiTE ( Yang et al 2019 ), SCSsim ( Yu et al 2020 ), SCSIM ( Giguere et al 2020 ), MosaicSim ( Srivatsa et al 2022 ), SCSilicon ( Feng and Chen 2022 ), and SimSCSnTree ( Mallory and Nakhleh 2022 ). Among these, SCSIM ( Giguere et al 2020 ) and SCSsim ( Yu et al , 2020 ) generate single-cell sequencing reads assuming biases from the whole-genome amplification (WGA) process, however neither approach models the evolutionary relationships between cells or subclones. MosaicSim ( Srivatsa et al 2022 ) is a more general next-generation sequencing (NGS) simulator tool that explicitly creates a phylogenetic tree of the tumor but is limited in the diversity of and user-control over possible CNAs.…”