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Accurate detection of somatic single-nucleotide variants from bulk RNA-seq data using RNA-MosaicHunter
August Yue Huang1,2,3, Yuchen Cheng1,4, Jayoung Ku1,2,3
1Division of Genetics and Genomics and Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, United States.
Nucleic Acids Research
|January 8, 2026
Summary
Somatic variants, or mutations, are linked to various disorders. A new tool, RNA-MosaicHunter, accurately detects these mutations from RNA sequencing data, aiding research in aging and diseases like Alzheimer's.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- Somatic variants contribute to non-cancerous disorders, developmental issues, and aging.
- Existing tools for somatic single-nucleotide variant (sSNV) detection are DNA-centric and often cancer-focused.
- There's a need for RNA sequencing-based sSNV detection in non-cancerous tissues.
Purpose of the Study:
- Introduce RNA-MosaicHunter, a novel bioinformatic tool for sSNV detection from bulk RNA sequencing data.
- Evaluate RNA-MosaicHunter's performance in accuracy and sensitivity.
- Apply RNA-MosaicHunter to large-scale datasets to explore somatic variants in aging and Alzheimer's disease.
Main Methods:
- Developed RNA-MosaicHunter for sSNV detection from RNA sequencing data.
- Benchmarked RNA-MosaicHunter using TCGA and cell-line mixture datasets.
- Applied the tool to Genotype Tissue Expression (GTEx) project data and Alzheimer's disease (AD) brain samples.
Main Results:
- RNA-MosaicHunter achieved high precision (94.7%-99.3%) in benchmarking.
- The tool identified mutational characteristics associated with normal aging in GTEx samples, outperforming previous methods.
- A significantly higher burden of sSNVs was observed in the cerebral cortex of Alzheimer's disease patients.
Conclusions:
- RNA-MosaicHunter provides accurate sSNV detection from RNA-seq data.
- The tool facilitates the profiling and characterization of somatic variants across diverse tissues and diseases.
- Findings suggest a potential role for sSNVs in Alzheimer's disease pathogenesis and normal aging.
