LongAGE

LongAGE defines breakpoints of genomic structural variants at single-nucleotide resolution by performing memory-efficient alignment with gap excision.

Key Features:

• Memory-efficient AGE implementation: LongAGE implements Alignment with Gap Excision (AGE) with a reduced memory footprint requiring less than hundreds of megabytes.
• Hirschberg algorithm: It uses a classical Hirschberg algorithm-based approach to lower memory usage when aligning long sequences with large gaps.
• Performance trade-off: LongAGE can be up to four times slower in runtime compared to AGE while maintaining high breakpoint accuracy.
• Long-read compatibility: The method has been demonstrated on Pacific Biosciences (PacBio) reads longer than 10 kilobases.
• Complex-region resolution: It resolves breakpoints of structural variants embedded within segmental duplications.
• Empirical evidence for mCNVs: Application to specific loci revealed different breakpoints for deletions and duplications at the same location, supporting multi-allelic copy number variant (mCNV) origins.
• Implementation: LongAGE is implemented in C++.

Scientific Applications:

• Breakpoint definition of structural variants: Defining single-nucleotide-resolution breakpoints of genomic structural variants, including deletions and duplications.
• Analysis of long-read sequencing data: Applying to PacBio long reads (greater than 10 kb) for SV breakpoint resolution.
• Study of segmental duplications: Resolving SV breakpoints within segmental duplications to investigate complex genomic regions.
• Investigation of multi-allelic CNVs: Providing direct evidence for mCNVs by distinguishing independent breakpoints for allelic variants.

Methodology:

LongAGE implements Alignment with Gap Excision (AGE) using a classical Hirschberg algorithm-based approach to reduce memory usage when aligning long sequences with large gaps.