Towards population-scale long-read sequencing

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 sequenci...

Full description

Saved in:
Bibliographic Details
Published in:Nature reviews. Genetics 2021-09, Vol.22 (9), p.572-587
Main Authors: De Coster, Wouter, Weissensteiner, Matthias H., Sedlazeck, Fritz J.
Format: Article
Language:English
Subjects:
631/114/2785
631/208/457
631/61/514
Agriculture
Animal Genetics and Genomics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Computational Biology - methods
Computer applications
DNA sequencing
Gene Function
Genome, Human
Genomics
Genomics - methods
Genotyping
High-Throughput Nucleotide Sequencing - methods
Human Genetics
Humans
Industrial Development - trends
Methods
Nucleotide sequencing
Population
Population genetics
Population studies
Review
Review Article
Reviews
Sequence Analysis, DNA - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Long-read sequencing at the population scale presents specific challenges but is becoming increasingly accessible. In this Review, Sedlazeck and colleagues discuss the major platforms and analytical tools, considerations in project design and challenges in scaling long-read sequencing to populations.
ISSN:1471-0056
1471-0064
DOI:10.1038/s41576-021-00367-3