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. 2021 Nov 8;22(1):543.
doi: 10.1186/s12859-021-04458-0.

VPMBench: a test bench for variant prioritization methods

Andreas Ruscheinski  1 , Anna Lena Reimler  2 , Roland Ewald  3 , Adelinde M Uhrmacher  2
Affiliations

VPMBench: a test bench for variant prioritization methods

Andreas Ruscheinski et al. BMC Bioinformatics. .

Abstract

Background: Clinical diagnostics of whole-exome and whole-genome sequencing data requires geneticists to consider thousands of genetic variants for each patient. Various variant prioritization methods have been developed over the last years to aid clinicians in identifying variants that are likely disease-causing. Each time a new method is developed, its effectiveness must be evaluated and compared to other approaches based on the most recently available evaluation data. Doing so in an unbiased, systematic, and replicable manner requires significant effort.

Results: The open-source test bench "VPMBench" automates the evaluation of variant prioritization methods. VPMBench introduces a standardized interface for prioritization methods and provides a plugin system that makes it easy to evaluate new methods. It supports different input data formats and custom output data preparation. VPMBench exploits declaratively specified information about the methods, e.g., the variants supported by the methods. Plugins may also be provided in a technology-agnostic manner via containerization.

Conclusions: VPMBench significantly simplifies the evaluation of both custom and published variant prioritization methods. As we expect variant prioritization methods to become ever more critical with the advent of whole-genome sequencing in clinical diagnostics, such tool support is crucial to facilitate methodological research.

Keywords: Bioinformatics; Evaluation; Software; Test bench; Variant prioritization.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the VPMBench architecture
Fig. 2
Fig. 2
Plots of the confusion matrices and ROC curves for fathmm-MKL (non-coding) and fathmm-MKL (coding), and CADD scores
Fig. 3
Fig. 3
Relative concordance of CADD, fathmm-MKL (coding), and fathmm-MKL (non-coding) for annual ClinVar releases
See this image and copyright information in PMC

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