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vcfsim: flexible simulation of all-sites VCFs with missing data.

Paimon Goulart1, Kieran Samuk2

  • 1Department of Computer Science and Engineering, The University of California, Riverside.

Biorxiv : the Preprint Server for Biology
|October 3, 2025
PubMed
Summary

Introducing vcfsim, a new tool for simulating all-sites VCFs. This tool accurately models missing genetic data and variable ploidy, crucial for population genetics research.

Keywords:
BenchmarkingCoalescentDemographyGenomic data analysisMissing dataPloidyPopulation geneticsSimulationSoftwareVariant Call Format (VCF)

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Area of Science:

  • Genomics
  • Bioinformatics
  • Population Genetics

Background:

  • Variant Call Format (VCF) files are standard for genetic variation data.
  • Standard VCFs omit invariant sites, conflating them with missing data.
  • Missing data can bias population genetic parameter estimation.

Purpose of the Study:

  • To address the lack of realistic simulation frameworks for all-sites VCFs.
  • To introduce a tool for generating biologically realistic all-sites VCFs with missing data and variable ploidy.

Main Methods:

  • Developed `vcfsim`, an open-source command-line tool.
  • Integrated `vcfsim` with the `msprime` coalescent simulation platform.
  • Implemented functions for simulating VCFs with variable ploidy and missing data.

Main Results:

  • `vcfsim` generates post-processed VCFs statistically identical to raw `msprime` output.
  • The tool accurately simulates missing data and variable ploidy, including sex chromosomes.
  • Simulations allow for exploration of intraindividual ploidy variation and population structures.

Conclusions:

  • `vcfsim` is a valuable, user-friendly tool for genomics research.
  • Applications include software benchmarking, population genetic inference, and machine learning model training.
  • Facilitates the study of missing data effects in genomic datasets.