More Efficient Genome Assembly Method Developed

A technique for reconstructing whole genomes on a personal computer has been developed by scientists at the Massachusetts Institute of Technology and the Institut Pasteur. This technique is about a hundred times faster than current approaches and uses one-fifth the resources, according to a study published today in Cell Systems.

“We can quickly assemble entire genomes and metagenomes, including microbial genomes, on a modest laptop computer,” says Bonnie Berger, an author of the study. “This ability is essential in assessing changes in the gut microbiome linked to disease and bacterial infections, such as sepsis, so that we can more rapidly treat them and save lives.”

Genome assembly projects have come a long way since the Human Genome Project. But while human genome assembly projects no longer take years, they still require several days and massive computer power. Third-generation sequencing technologies offer terabytes of high-quality genomic sequences with tens of thousands of base pairs, yet genome assembly using such an immense quantity of data has proved challenging.

To approach genome assembly more efficiently than current techniques, which involve making pairwise comparisons between all possible pairs of reads, Berger and colleagues turned to language models. Building from the concept of a de Bruijn graph, a simple, efficient data structure used for genome assembly, the researchers developed a minimizer-space de Bruin graph (mdBG), which uses short sequences of nucleotides called minimizers instead of single nucleotides.

“Our minimizer-space de Bruijn graphs store only a small fraction of the total nucleotides, while preserving the overall genome structure, enabling them to be orders of magnitude more efficient than classical de Bruijn graphs,” says Berger.

The researchers applied their method to assemble real HiFi data for Drosophila melanogaster fruit flies, as well as human genome data provided by Pacific Biosciences. When they evaluated the resulting genomes, Berger and colleagues found that their mdBG-based software required about 33 times less time and 8 times less random-access memory computing hardware than other genome assemblers. Their software performed genome assembly for the HiFi human data 81 times faster with 18 times less memory usage than the Peregrine assembler and 338 times faster with 19 times less memory usage than the hifiasm assembler.

Next, Berger and colleagues used their method to construct an index for a collection of 661,406 bacterial genomes, the largest collection of its kind to date. They found that the novel technique could search the entire collection for antimicrobial resistance genes in 13 minutes—a process that took 7 hours using standard sequence alignment.