Multiz

Multiz performs dynamic-programming-based multiple genome alignments to construct threaded blocksets for comparative genomics of highly rearranged or incompletely sequenced genomes.

Key Features:

• Threaded blockset alignment: Constructs threaded blocksets as a generalization of traditional multiple sequence alignments to maintain consistent matching segments across sequences.
• Rearrangement handling: Optimized for aligning highly rearranged genomes by preserving segment order and orientation within threaded blocksets.
• Limitations on inversions and duplications: Does not address inversions or duplications within the alignment process.
• Genome size compatibility: Scales to megabase-sized regions and has been applied to multiple mammalian genomes.
• Reference projection capability: Outputs can be projected onto any chosen reference genome to yield consistent predictions of orthologous genomic positions.
• Accuracy evaluation: Performance has been evaluated using simulation programs that mimic evolutionary changes, demonstrating superior accuracy relative to earlier alignment tools.
• Application to genome browsers: Has been used to generate whole-genome multiple alignments for resources such as the Santa Cruz (UCSC) Genome Browser.

Scientific Applications:

• Comparative genomics: Enables identification of conserved elements and evolutionary relationships by aligning large genomic regions across species.
• Orthology prediction: Supports prediction of orthologous genomic positions through alignment projection onto reference genomes.
• Genomic rearrangement studies: Facilitates study of structural variation and its evolutionary implications by handling highly rearranged sequences.

Methodology:

Multiz uses a dynamic-programming-based multiple alignment approach within the TBA (Threaded Blockset Aligner) framework to construct threaded blocksets under assumptions of consistent sequence order and orientation.