Towards population-scale long-read sequencing

Nat Rev Genet. 2021 Sep;22(9):572-587. doi: 10.1038/s41576-021-00367-3. Epub 2021 May 28.


Long-read sequencing technologies have now reached a level of accuracy and yield that allows their application to variant detection at a scale of tens to thousands of samples. Concomitant with the development of new computational tools, the first population-scale studies involving long-read sequencing have emerged over the past 2 years and, given the continuous advancement of the field, many more are likely to follow. In this Review, we survey recent developments in population-scale long-read sequencing, highlight potential challenges of a scaled-up approach and provide guidance regarding experimental design. We provide an overview of current long-read sequencing platforms, variant calling methodologies and approaches for de novo assemblies and reference-based mapping approaches. Furthermore, we summarize strategies for variant validation, genotyping and predicting functional impact and emphasize challenges remaining in achieving long-read sequencing at a population scale.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Computational Biology / methods*
  • Genome, Human*
  • Genomics / methods*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Industrial Development / trends*
  • Sequence Analysis, DNA / methods*