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bioRxiv · 10.64898/2026.05.08.723876

MucOneUp: A Simulation Framework for MUC1-VNTR Variant Benchmarking

Popp, B.·Saei, H.
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Abstract

SummaryVariable number tandem repeats (VNTRs) in the MUC1 gene cause autosomal dominant tubulointerstitial kidney disease when disrupted by frameshift variants, but the GC-rich 60-bp repeat structure (20-125 copies) challenges variant detection. While tools like VNtyper enable MUC1 variant calling, no gold-standard benchmarking datasets exist for systematic performance evaluation. We present MucOneUp, a specialized simulation framework for generating MUC1-VNTR reference sequences with targeted variants and platform-specific sequencing reads (Illumina, Oxford Nanopore, PacBio). MucOneUp employs Markov chain-based repeat generation, supports diploid simulation with customizable variant placement, and includes additional analysis modules for SNaPshot assay simulation and exploratory frameshift analysis. We validate MucOneUp through a multi-variant, cross-platform benchmark of six tool-platform combinations using 13 distinct frameshift variants and investigate VNTR length effects on detection. Availability and implementationMucOneUp is accessible at no cost under the MIT License at https://github.com/berntpopp/MucOneUp and archived on Zenodo (DOI: 10.5281/zenodo.19740406). Contactbernt.popp@charite.de Supplementary informationSupplementary data are provided with this manuscript.

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Popp, B., Saei, H.. 2026-05-12. MucOneUp: A Simulation Framework for MUC1-VNTR Variant Benchmarking. https://doi.org/10.64898/2026.05.08.723876

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