NextSV

NextSV integrates multiple aligners and structural variant callers to detect deletions, insertions, duplications, and inversions from low-coverage Pacific Biosciences (PacBio) long-read human whole-genome sequencing data, producing sensitive and stringent call sets to balance recall and precision.

Key Features:

• Meta-caller integration: Integrates three aligners and three distinct SV callers into a single meta-caller framework for SV detection.
• SV type support: Detects deletions, insertions, duplications, and inversions.
• Dual call sets: Produces a sensitive call set aimed at maximizing recall and a stringent call set focused on enhancing precision.
• Low-coverage optimization: Optimized for low-coverage PacBio long-read sequencing data and evaluated around ~10X coverage.
• Benchmarking metrics: Reports precision, recall, and F1 score for comparative performance assessment.
• Dataset evaluation: Benchmarked using NA12878 and HX1 genomes across varying PacBio coverages.
• Mendelian error analysis: Assesses Mendelian errors using an Ashkenazi Jewish trio to evaluate inherited SV detection.
• Coverage recommendation: Indicates that approximately 10X PacBio coverage provides a balance between sequencing cost and effective SV detection.

Scientific Applications:

• Human structural variant discovery: Detection of deletions, insertions, duplications, and inversions from low-coverage PacBio whole-genome data.
• SV caller and aligner comparison: Comparative evaluation of multiple aligners and SV callers via meta-calling to improve call reliability.
• Mendelian inheritance studies: Analysis of inherited structural variants and Mendelian error rates in pedigree datasets such as the Ashkenazi Jewish trio.
• Sequencing design guidance: Informing experimental design and coverage decisions for long-read sequencing projects targeting SV discovery.

Methodology:

Integrates three aligners and three SV callers into a meta-caller workflow, generates sensitive and stringent call sets, benchmarks performance on NA12878 and HX1 under varying PacBio coverages (reporting deletion recall ~93.5–94.1% and insertion recall ~87.9–93.2% near 10X and F1-based precision/accuracy), and assesses Mendelian errors using an Ashkenazi Jewish trio.