Direct probabilistic quantification of mosaic loss of chromosome Y from sequencing data

Authors

Lin, J.-R., Chang, Y.-C., Maslov, A. Y., Song, Y., Gao, T., Shan, J., Bennett, D. A., Milman, S., Barzilai, N., Vijg, J., Montagna, C., Zhang, Z.

Abstract

Loss of chromosome Y (LOY) is the most common aneuploidy in aging men and is increasingly recognized as a marker of aging and genomic instability. Because LOY occurs in mosaic form, its degree reflects the fraction of cells lacking the Y chromosome. Existing SNP-array- and sequencing-based methods rely largely on single genomic features and indirect transformations to estimate this fraction. We developed BaySeq-Y, a Bayesian method that directly estimates LOY mosaicism from sequencing data using VCF files with read depth (DP) and allelic depth (AD). Within a rigorous Bayesian framework, BaySeq-Y integrates complementary LOY-associated genomic features, including decreased read depth and allelic imbalance, and can additionally leverage haplotype phasing to improve precision. In simulations and fluorescence in situ hybridization validation (FISH), BaySeq-Y provided accurate estimates and outperformed existing methods. Applications to ROSMAP and GTEx supported its biological relevance through transcriptomic validation, demonstrating its utility for quantifying LOY across diverse sequencing datasets.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 02 Jul 2026.

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