The new metagenome assembler can generate accurate DNA sequences

Metagenomics often involves the sequencing of DNA samples which can only be described as “complicated”. Such DNA exhibits high heterogeneity, which can cause interspecies disassembly.

These disassemblies threaten the very purpose of metagenome sequencing, which is to comprehensively study the gene pool, generating multiple draft genomes in a given sample. This problem is further complicated by the presence of certain organisms in these samples which cannot be cultured using standard microbiological techniques. How can this cascade of problems be solved?

Tokyo Tech scientists now have the answer. They developed a new metagenome assembler called MetaPlatanus, which can generate accurate DNA sequences, including those of non-cultured organisms. Their groundbreaking findings were published as a research article in Research on nucleic acids.

MetaPlatanus uses accurate readings of short DNA sequences to assemble contig. Contigs are slightly longer stretches of the DNA sequence that are analogous to the puzzle pieces in the larger genome. Contigs are assembled into larger chromosomal-scale scaffolds using repeatedly inputs such as long-range sequence links, species-specific sequence compositions, depth of coverage, and binning information.

Explaining the choice of inputs for generating MetaPlatanus-based scaffolds, Dr. Rei Kajitani, Assistant Professor at the School of Life Science and Technology, Tokyo Tech, and lead scientist of the study, says: “We use a hybrid method of assembling the metagenome that not only utilizes the advantages of both short-range and long-range sequence reads, but also compensates for the shortcomings posed by both read lengths and the sample itself. “

We applied binning to link sequences divided by difficult-to-assemble regions, such as repetitive ones. Our approach is new as the combination of collection and assembly processes has not been implemented as a public tool, so far!“

Dr Rei Kajitani, Lead Scientist and Assistant Professor, School of Life Science and Technology, Tokyo Institute of Technology

Dr. Kajitani and his team left no stone unturned in checking the accuracy of the results produced by MetaPlatanus. In this regard, they performed a process called benchmarking using dummy datasets of known bacteria. Unsurprisingly, MetaPlatanus provided highly contiguous results, with very few interspecies disassembly.

Notably, while testing the accuracy of MetaPlatanus with previously published human gut data, it also assembled many biologically important elements, including coding genes, gene clusters, viral sequences, and more than half of the bacterial genomes.

Furthermore, compared to other existing tools, only MetaPlatanus was able to perform an almost complete assembly of some high-abundance bacterial genomes, during benchmarking using already published human saliva data.

In fact, Dr. Kajitani and his team appear to have found metagenomic gold with MetaPlatanus. Excited by the potential applications of MetaPlatanus, he exclaims, “We believe the metagenome assembler we developed at Tokyo Tech could help examine the contexts of sequence elements spreading across the genome, which could have countless real-world applications.”

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Undoubtedly, this study could prove to be a milestone in the field of metagenomics.