Long reads vs short reads: two ways to read a genome

How do we read a genome? This video explains short-read sequencing (Illumina) and long-read sequencing (PacBio and Oxford Nanopore): how each one works, what a read is, and why read length matters. It starts from the story of the missing 8% of the human reference genome, which was completed in 2022 with long reads. It draws on four papers. Goodwin et al. (Cold Spring Harbor Laboratory and the University of California, Davis; Nature Reviews Genetics, 2016) is a review of ten years of next-generation sequencing. Logsdon et al. (University of Washington School of Medicine; Nature Reviews Genetics, 2020) is a review of long-read human genome sequencing. Wenger et al. (Pacific Biosciences and partner institutions; Nature Biotechnology, 2019) describes accurate circular consensus (HiFi) reads. Nurk et al. (the Telomere-to-Telomere Consortium; first author at the National Human Genome Research Institute; Science, 2022) reports the complete sequence of a human genome. Traditional Chinese subtitles are available (turn on CC). CHAPTERS 0:00 The missing eight percent 0:56 What a read is 1:49 Short reads 2:56 Long reads: PacBio 4:02 Long reads: Oxford Nanopore 5:08 Why length matters 6:49 What each is good for 7:55 The complete genome REFERENCES Goodwin S., McPherson J.D., McCombie W.R. Coming of age: ten years of next-generation sequencing technologies. Nature Reviews Genetics, 17, 333 (2016; published online 2016-05-17). https://doi.org/10.1038/nrg.2016.49 Logsdon G.A., Vollger M.R., Eichler E.E. Long-read human genome sequencing and its applications. Nature Reviews Genetics, 21, 597-614 (2020; published online 2020-06-05). https://doi.org/10.1038/s41576-020-02... Wenger A.M. et al. Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome. Nature Biotechnology, 37, 1155-1162 (2019). https://doi.org/10.1038/s41587-019-02... Nurk S. et al. The complete sequence of a human genome. Science, 376, 44-53 (2022-04-01). https://doi.org/10.1126/science.abj6987