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. 2024 Feb 6;4(1):vbae017.
doi: 10.1093/bioadv/vbae017. eCollection 2024.

ZygosityPredictor

Marco Rheinnecker  1 , Martina Fröhlich  1   2 , Marc Rübsam  1 , Nagarajan Paramasivam  1 , Christoph E Heilig  2   3 , Stefan Fröhling  2   3 , Richard F Schlenk  2   4   5   6 , Barbara Hutter  1   2 , Daniel Hübschmann  1   2   7   8
Affiliations

ZygosityPredictor

Marco Rheinnecker et al. Bioinform Adv. .

Abstract

Summary: ZygosityPredictor provides functionality to evaluate how many copies of a gene are affected by mutations in next generation sequencing data. In cancer samples, the tool processes both somatic and germline mutations. In particular, ZygosityPredictor computes the number of affected copies for single nucleotide variants and small insertions and deletions (Indels). In addition, the tool integrates information at gene level via phasing of several variants and subsequent logic to derive how strongly a gene is affected by mutations and provides a measure of confidence. This information is of particular interest in precision oncology, e.g. when assessing whether unmutated copies of tumor-suppressor genes remain.

Availability and implementation: ZygosityPredictor was implemented as an R-package and is available via Bioconductor at https://bioconductor.org/packages/ZygosityPredictor. Detailed documentation is provided in the vignette including application to an example genome.

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Conflict of interest statement

None declared.

Figures

Figure 1.
Figure 1.
Schematic for determination of the number of affected copies for a somatic or germline mutation in a tumor sample. Tumor cells are depicted in red, admixed healthy cells are depicted in blue. The relevant parameters are color-coded. Calculation of affected copies are depicted in grey boxes.
Figure 2.
Figure 2.
Phasing. (A) Schematic for read-level phasing in a diploid genome with two variants in a region of interest. On the left, the variants are located on different alleles; on the right, variants are located on the same allele and therefore leave one wt allele intact. Below, repercussions on NGS reads/read-pairs are shown. (B) Example of a genomic region with 7 mutations/variants to be phased. Variants are depicted in red and SNPs (germline variation including polymorphisms) in blue. AIP, allelic imbalance phasing. (C) Phasing-matrix of the same example as in (B) with detailed indirect reasoning for all pairwise variant combinations that cannot be determined by direct phasing. Colors of phased combinations correspond to read-pair colors in (B).
See this image and copyright information in PMC

References

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