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"We can quickly assemble entire genomes and metagenomics, including microbial genomes, on an ordinary laptop computer," said Bonnie Berger, a professor of mathematics at MIT's Computer Science and Artificial Intelligence Laboratory and the author of the study
.
"This ability is essential to assess changes in the gut microbiota related to diseases and bacterial infections (such as sepsis) so that we can treat them faster and save lives
Since the Human Genome Project (Human Genome Project), the genome assembly project has made considerable progress
.
In 2003, the Human Genome Project completed the first complete assembly of the human genome at a cost of approximately US$2.
In order to achieve genome assembly more efficiently than current technologies, Bonnie Berger and his colleagues turned to language models
.
Current technology requires pairwise comparisons of all possible reading combinations
Berger said: "Our minimal space de Bruijn diagrams store only a small part of the total nucleotides while preserving the entire genome structure, making them orders of magnitude more efficient than the classic de Bruijn diagrams
.
"
The researchers applied their method to collect real HiFi data of Drosophila melanogaster (almost perfect single-molecule reading accuracy) and human genome data provided by Pacific Biosciences (PacBio)
.
When Berger and his colleagues evaluated the resulting genomes, compared with other genome assemblers, mdbg-based software required 33 times less time and random access memory (RAM) computing hardware 8 times less
Next, Berger and his colleagues used their method to build an index of 661,406 bacterial genomes, which is by far the largest of its kind
.
They found that this new technology can search for all antimicrobial resistance genes in 13 minutes, while it takes 7 hours to use standard sequence alignment
Berger said: "We know that this method is effective, but we don't know that after further optimizing the code, it can scale so well on real data
.
"
Rayan Chikhi, a researcher and team leader at the Pasteur Institute and one of the authors of the study, said: "The overall idea is feasible and does not require some usually expensive pre-processing steps, such as the mistakes made by most other genome assembly methods.
Correction
.
"
Berger added: "We can also process sequencing data
with an error rate of up to 4% .
" "As the price of long-read sequencers with different error rates drops rapidly, this capability opens the door to the democratization of sequencing data analysis
Berger pointed out that although the method currently performs best when processing PacBio HiFi readings, the error rate is much lower than 1%, and it may soon be compatible with the ultra-long reading of Oxford nanopores.
The current errors of Oxford nanopores The rate is 5-12%, but it may soon provide 4% reads
.
Berger said: "This can help field scientists build rapid genomic testing sites and go beyond PCR and marker arrays that might miss important differences between genomes
.
"
This work was supported by the National Institutes of Health, ANR Inception, PRAIRIE and PANGAIA
.
Journal Reference :
Barış Ekim, Bonnie Berger, Rayan Chikhi.
Minimizer-space de Bruijn graphs: Whole-genome assembly of long reads in minutes on a personal computer .
Cell Systems , 2021; DOI: 10.
1016/j.
cels.
2021.
08.
009