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Long Read Sequencing

Guest Editors: Barbara Wold and Kin Fai Au

In this new special issue in Genome Biology, we present a series of papers using Long-read sequencing. Long-read sequencing technologies provide unprecedented opportunities to solve many complex biomedical problems, especially for those unsolved by short-read sequencing. Their long read lengths offer unambiguous mappability for reliable identification of genomic events and are also informative for long-range analyses, such as haplotyping and genome assembly. In addition, the long-read techniques, PacBio and Oxford Nanopore Technologies sequence single molecules and can detect canonical nucleotides as well as base modifications. Both experimental and computational method developments are needed to fully utilize long-read sequencing while accounting for their corresponding weakness (e.g. higher error rates). To translate the technological advances into biomedical breakthroughs, other avenues of research are exploring innovative applications of long-read sequencing to significant biomedical contexts.

(Image by Jane Cha at the Jackson Laboratory)



  1. Despite recent improvements in basecalling accuracy, nanopore sequencing still has higher error rates on short-tandem repeats (STRs). Instead of using basecalled reads, we developed DeepRepeat which converts i...

    Authors: Li Fang, Qian Liu, Alex Mas Monteys, Pedro Gonzalez-Alegre, Beverly L. Davidson and Kai Wang
    Citation: Genome Biology 2022 23:108
  2. Adaptive sampling is a method of software-controlled enrichment unique to nanopore sequencing platforms. To test its potential for enrichment of rarer species within metagenomic samples, we create a synthetic ...

    Authors: Samuel Martin, Darren Heavens, Yuxuan Lan, Samuel Horsfield, Matthew D. Clark and Richard M. Leggett
    Citation: Genome Biology 2022 23:11
  3. In cancer, fusions are important diagnostic markers and targets for therapy. Long-read transcriptome sequencing allows the discovery of fusions with their full-length isoform structure. However, due to higher ...

    Authors: Nadia M. Davidson, Ying Chen, Teresa Sadras, Georgina L. Ryland, Piers Blombery, Paul G. Ekert, Jonathan Göke and Alicia Oshlack
    Citation: Genome Biology 2022 23:10
  4. Long-read de novo genome assembly continues to advance rapidly. However, there is a lack of effective tools to accurately evaluate the assembly results, especially for structural errors. We present Inspector, ...

    Authors: Yu Chen, Yixin Zhang, Amy Y. Wang, Min Gao and Zechen Chong
    Citation: Genome Biology 2021 22:312
  5. A modified Chromium 10x droplet-based protocol that subsamples cells for both short-read and long-read (nanopore) sequencing together with a new computational pipeline (FLAMES) is developed to enable isoform disc...

    Authors: Luyi Tian, Jafar S. Jabbari, Rachel Thijssen, Quentin Gouil, Shanika L. Amarasinghe, Oliver Voogd, Hasaru Kariyawasam, Mei R. M. Du, Jakob Schuster, Changqing Wang, Shian Su, Xueyi Dong, Charity W. Law, Alexis Lucattini, Yair David Joseph Prawer, Coralina Collar-Fernández…
    Citation: Genome Biology 2021 22:310
  6. We present SquiggleNet, the first deep-learning model that can classify nanopore reads directly from their electrical signals. SquiggleNet operates faster than DNA passes through the pore, allowing real-time c...

    Authors: Yuwei Bao, Jack Wadden, John R. Erb-Downward, Piyush Ranjan, Weichen Zhou, Torrin L. McDonald, Ryan E. Mills, Alan P. Boyle, Robert P. Dickson, David Blaauw and Joshua D. Welch
    Citation: Genome Biology 2021 22:298
  7. Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylati...

    Authors: Yang Liu, Wojciech Rosikiewicz, Ziwei Pan, Nathaniel Jillette, Ping Wang, Aziz Taghbalout, Jonathan Foox, Christopher Mason, Martin Carroll, Albert Cheng and Sheng Li
    Citation: Genome Biology 2021 22:295
  8. The rise in throughput and quality of long-read sequencing should allow unambiguous identification of full-length transcript isoforms. However, its application to single-cell RNA-seq has been limited by throug...

    Authors: Elisabeth Rebboah, Fairlie Reese, Katherine Williams, Gabriela Balderrama-Gutierrez, Cassandra McGill, Diane Trout, Isaryhia Rodriguez, Heidi Liang, Barbara J. Wold and Ali Mortazavi
    Citation: Genome Biology 2021 22:286
  9. While long-read sequencing allows for the complete assembly of bacterial genomes, long-read assemblies contain a variety of errors. Here, we present Trycycler, a tool which produces a consensus assembly from m...

    Authors: Ryan R. Wick, Louise M. Judd, Louise T. Cerdeira, Jane Hawkey, Guillaume Méric, Ben Vezina, Kelly L. Wyres and Kathryn E. Holt
    Citation: Genome Biology 2021 22:266
  10. We develop the Oncogene Concatenated Enriched Amplicon Nanopore Sequencing (OCEANS) method, in which variants with low variant allele frequency (VAFs) are amplified and subsequently concatenated for Nanopore S...

    Authors: Deepak Thirunavukarasu, Lauren Y. Cheng, Ping Song, Sherry X. Chen, Mitesh J. Borad, Lawrence Kwong, Phillip James, Daniel J. Turner and David Yu Zhang
    Citation: Genome Biology 2021 22:227
  11. Currently, different sequencing platforms are used to generate plant genomes and no workflow has been properly developed to optimize time, cost, and assembly quality. We present LeafGo, a complete de novo plan...

    Authors: Patrick Driguez, Salim Bougouffa, Karen Carty, Alexander Putra, Kamel Jabbari, Muppala Reddy, Richard Soppe, Ming Sin Cheung, Yoshinori Fukasawa and Luca Ermini
    Citation: Genome Biology 2021 22:256
  12. Tandem repeat (TR) expansion is the underlying cause of over 40 neurological disorders. Long-read sequencing offers an exciting avenue over conventional technologies for detecting TR expansions. Here, we prese...

    Authors: Readman Chiu, Indhu-Shree Rajan-Babu, Jan M. Friedman and Inanc Birol
    Citation: Genome Biology 2021 22:224
  13. The origin of sex chromosomes requires the establishment of recombination suppression between the proto-sex chromosomes. In many fish species, the sex chromosome pair is homomorphic with a recent origin, provi...

    Authors: Lingzhan Xue, Yu Gao, Meiying Wu, Tian Tian, Haiping Fan, Yongji Huang, Zhen Huang, Dapeng Li and Luohao Xu
    Citation: Genome Biology 2021 22:203
  14. Resistance to CD19-directed immunotherapies in lymphoblastic leukemia has been attributed, among other factors, to several aberrant CD19 pre-mRNA splicing events, including recently reported excision of a cryptic...

    Authors: Laura Schulz, Manuel Torres-Diz, Mariela Cortés-López, Katharina E. Hayer, Mukta Asnani, Sarah K. Tasian, Yoseph Barash, Elena Sotillo, Kathi Zarnack, Julian König and Andrei Thomas-Tikhonenko
    Citation: Genome Biology 2021 22:190
  15. Long-read RNA sequencing (RNA-seq) technologies can sequence full-length transcripts, facilitating the exploration of isoform-specific gene expression over short-read RNA-seq. We present LIQA to quantify isofo...

    Authors: Yu Hu, Li Fang, Xuelian Chen, Jiang F. Zhong, Mingyao Li and Kai Wang
    Citation: Genome Biology 2021 22:182
  16. Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. However, few studies have examined the role of SVs in high-altitude adaptation and little...

    Authors: Cheng Quan, Yuanfeng Li, Xinyi Liu, Yahui Wang, Jie Ping, Yiming Lu and Gangqiao Zhou
    Citation: Genome Biology 2021 22:159