Progressive Cactus is a multiple-genome aligner for the thousand-genome era

Area of Science:

• Genomics
• Bioinformatics
• Computational Biology

Background:

• Sequencing costs have decreased, and third-generation technologies have improved, leading to a rapid increase in new genome assemblies.
• The NCBI database saw a >50% rise in vertebrate genome assemblies (to 1,485) between July 2018 and July 2019.
• New human de novo assemblies allow analysis of small polymorphisms and large structural differences.

Purpose of the Study:

• To address the challenges posed by the unprecedented scale of genomic data for evolutionary insights.
• To adapt existing genome analysis methods for increased data scale.
• To develop a scalable multiple genome alignment program.

Main Methods:

• Progressive extensions were made to the Cactus program, a reference-free multiple genome alignment tool.
• The enhanced program, Progressive Cactus, was designed to handle tens to thousands of large vertebrate genomes.
• The method was tested on an alignment of over 600 amniote genomes.

Main Results:

• Progressive Cactus enables reference-free alignment of tens to thousands of large vertebrate genomes.
• The program maintains high alignment quality even with a large number of genomes.
• The study produced the largest multiple vertebrate genome alignment to date, with over 600 amniote genomes.

Conclusions:

• Progressive Cactus overcomes the scalability limitations of previous methods for multiple genome alignment.
• The developed method facilitates the analysis of large-scale genomic data, enabling new insights into genome evolution.
• This advancement supports the analysis of thousands of genomes, pushing the boundaries of comparative genomics.