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Updated: Jun 10, 2026
14:06
Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
Published on: June 23, 2012
Structural variant calling using Sniffles2
Luis F Paulin1, Hermann Romanek1, Farhang Jaryani1,2,3
1Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Nature Protocols
|June 8, 2026
Summary
Sniffles2 software reliably detects structural variants (SVs) from long-read sequencing data. This protocol details its use for germline, mosaic, and joint SV calling in various applications, offering high precision and speed.
Area of Science:
- Genomics
- Bioinformatics
- Computational Biology
Background:
- Structural variants (SVs) are common genomic alterations with significant roles in evolution, disease, and gene regulation.
- Accurate SV detection is crucial for understanding genetic variation and its impact.
Purpose of the Study:
- To provide a comprehensive protocol for utilizing Sniffles2 (v2.6.3) for precise identification of germline and mosaic structural variants.
- To detail SV joint calling capabilities for tumor/normal and family trio analyses, scalable to population studies.
Main Methods:
- Utilizing Sniffles2 software for structural variant detection from long-read sequencing data.
- Implementing protocols for germline, mosaic (5-22% VAF), and joint SV calling.
- Benchmarking Sniffles2 against existing tools for precision and speed.
Main Results:
- Sniffles2 demonstrates high precision in detecting structural variants across various types (deletions, duplications, insertions, inversions, translocations).
- The tool accurately identifies low-variant allele fraction mosaic SVs.
- Sniffles2 achieves rapid SV calling, processing a 40x human genome in approximately 34 CPU minutes.
Conclusions:
- Sniffles2 is a fast, precise, and user-friendly tool for comprehensive structural variant analysis using long-read sequencing.
- The detailed protocol enables accurate germline and mosaic SV detection and joint calling for diverse research applications.
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