Duplex-Indel: a Snakemake pipeline for somatic Indel calling in Tn5 transposase-based duplex sequencing data

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Somatic mutations, including small insertions and deletions (Indels), are crucial in cancer development.
• Duplex sequencing offers high accuracy for detecting low-frequency variants.
• Existing methods may not fully leverage duplex sequencing for Indel detection.

Purpose of the Study:

• To introduce Duplex-Indel, a novel Snakemake workflow.
• To enable accurate detection of somatic Indels from Tn5 transposase-based duplex sequencing data.
• To enhance mutation calling accuracy at the single-molecule level.

Main Methods:

• Developed a Snakemake workflow named Duplex-Indel.
• Implemented a consensus-based approach requiring support from both DNA strands for Indel identification.
• Applied the workflow to Tn5 transposase-based duplex sequencing data.

Main Results:

• Duplex-Indel successfully detects somatic small insertions and deletions (Indels).
• The workflow enhances mutation calling accuracy by minimizing technical artifacts.
• Demonstrated accuracy and robustness using cancer cell line data.

Conclusions:

• Duplex-Indel is a robust tool for identifying somatic Indels in duplex sequencing data.
• The consensus approach improves the reliability of single-molecule mutation detection.
• This workflow expands the utility of duplex sequencing for cancer genomics research.