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

By J. Armstrong, Glenn Hickey, Mark Diekhans, Ian T. Fiddes, Adam M. Novak, A. Deran, Qi Fang, Duo Xie, Shaohong Feng, Josefin Stiller and 11 more. Nature, 2020

445 citations recorded by the source corpus.

New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies1–3. For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies5 are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus6, a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far. The Progressive Cactus program can create reference-free alignments of hundreds of large vertebrate genomes efficiently, and is used for the alignment of more than 600 amniote genomes.

Subfields: Genetics, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/3c8a35dd03a8d34ffc98e86644436abbdc0ec4e8

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

In Plant Science

Citations in the corpus

A draft human pangenome reference (2022, methodology): “MC extends the Minigraph pangenome with a base-level alignment of the homology relationships between the assemblies using the Cactus genome aligner (Armstrong et al., 2020), while retaining the structure of the Minigraph pangenome.”
GENCODE 2021 (2020, methodology): “For example, we have used Cactus to create a 600-way vertebrate whole genome alignment incorporating data from the 200 Mammals and Bird 10K projects as the basis of a single base-pair resolution map of evolutionary selection (20).”
The UCSC Genome Browser database: 2023 update (2022, unknown): “There is also now a 241-way Cactus (25,26) comparative genomics alignment track on hg38 generated by the Zoono-mia Project (27), which is the largest conservation track in the Genome Browser.”
Ensembl 2022 (2021, methodology): “We have deployed the Cactus (9) multiple genome aligner software, which is able to compute high quality multiple genome alignments with thousands of genomes in linear time.”