%0 Journal Article %J Nat Rev Genet %D 2021 %T Towards population-scale long-read sequencing. %A De Coster, Wouter %A Weissensteiner, Matthias H %A Sedlazeck, Fritz J %K Computational Biology %K Genome, Human %K Genomics %K High-Throughput Nucleotide Sequencing %K Humans %K Industrial Development %K Sequence Analysis, DNA %X

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.

%B Nat Rev Genet %V 22 %P 572-587 %8 2021 09 %G eng %N 9 %1 https://www.ncbi.nlm.nih.gov/pubmed/34050336?dopt=Abstract %R 10.1038/s41576-021-00367-3