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Long-Read Sequencing: Nature’s Method of the Year 2022

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  • Long-Read Sequencing: Nature’s Method of the Year 2022

    This week Nature Methods announced long-read sequencing as their Method of the Year 2022.

    Their choice is no surprise, as the year was filled with groundbreaking research exemplifying the importance of long-read sequencing in genomics most notably, the Telomere-to-Telomere (T2T) Consortium’s achievement of the first complete human genome and their follow-up of the first complete Y chromosome. These tasks would not have been possible without the use of long-read sequencing.

    The two primary technologies for long-read sequencing are Pacific Biosciences’ Single Molecule Real-Time (SMRT) sequencing and Oxford Nanopore Technologies’ nanopore sequencing. Although their sequencing methods are vastly different, both have contributed considerably to the advancement of genomics.

    Long-read instruments have allowed researchers to fill in the gaps and complex regions of genomes that have been historically difficult to process using short reads alone. Their constant development has placed their sequencing accuracy on par with leading short-read sequencers. Collaborations between companies like Google and Pacific Biosciences have facilitated improvements for long-read data analysis through advanced statistical and machine learning methods

    Utilization of long-read sequencing will enable researchers to interpret difficult sections of the genome, such as highly repetitive regions and complex structural variations, as well as isoform structure and expression from transcriptomes. Larger collaborations from the Vertebrate Genomes Project are applying this technology to produce high quality genomes of a variety of species.

    The fields of epigenomics and epitranscriptomics are also benefiting greatly from long reads. Nanopore sequencing has the ability to detect base modifications on native molecules allowing researchers to learn more about their functions without extensive processing. In addition, microbial genomics has utilized long-read sequencing to improve identification of microbes within a mixed culture. For instance, the HiFi reads from Pacific Biosciences has enhanced the process of creating metagenome-assembled genomes (MAGs).

    Pacific Biosciences and Oxford Nanopore Technologies are continuing to release and develop new instruments, while additional approaches to long-read sequencing (Illumina’s Infinity and Element Bioscience’s LoopSeq) have also been recently announced.

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