AGE

AGE performs alignment of sequences containing structural variations to determine single-nucleotide breakpoints and support reconstruction of variant-aware genome sequences.

Key Features:

• Optimal Alignment Algorithm: Implements a dynamic-programming algorithm specifically tailored to align sequences containing structural variations.
• Gap Excision Technique: Performs large-gap jumps between precisely aligned flanking ends to represent insertions, deletions, duplications, inversions, and complex multi-gap events.
• End-to-End Alignment: Simultaneously aligns both the 5' and 3' ends of sequences to maximize the total alignment score across regions containing SVs.
• Memory Efficiency: Designed for memory efficiency to handle alignment of long contigs.
• Extensibility: Supports extensions for tandem duplications, inversions, and complex events involving two large gaps.

Scientific Applications:

• Breakpoint Determination: Determines breakpoints at single-nucleotide resolution to enable classification and functional impact assessment of structural variations.
• Genome Reconstruction: Aids reconstruction of personal genome sequences by providing alignments that account for structural variations.
• Standardization Efforts: Has been applied to align locally assembled contigs to the human reference genome in large-scale projects such as the 1000 Genomes Project to standardize breakpoint determination.

Methodology:

Formulates SV alignment as a computational problem solved by a dynamic-programming approach that simultaneously aligns sequence ends and introduces large-gap jumps to span structural-variation regions while maximizing alignment scores.