2-AIN-506 a 2-AIN-252: Seminár z bioinformatiky (2) a (4)
Leto 2020

Rory Bowden, Robert W. Davies, Andreas Heger, Alistair T. Pagnamenta, Mariateresa {de Cesare}, Laura E. Oikkonen, Duncan Parkes, Colin Freeman, Fatima Dhalla, Smita Y. Patel, Niko Popitsch, Camilla L. C. Ip, Hannah E. Roberts, Silvia Salatino, Helen Lockstone, Gerton Lunter, Jenny C. Taylor, David Buck, Michael A. Simpson, Peter Donnelly. Sequencing of human genomes with nanopore technology. Nat Commun, 10(1):1869. 2019.

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Whole-genome sequencing (WGS) is becoming widely used in clinical medicine in
diagnostic contexts and to inform treatment choice. Here we evaluate the
potential of the Oxford Nanopore Technologies (ONT) MinION long-read sequencer
for routine WGS by sequencing the reference sample NA12878 and the genome of an
individual with ataxia-pancytopenia syndrome and severe immune dysregulation. We 
develop and apply a novel reference panel-free analytical method to infer and
then exploit phase information which improves single-nucleotide variant (SNV)
calling performance from otherwise modest levels. In the clinical sample, we
identify and directly phase two non-synonymous de novo variants in SAMD9L, (OMIM 
#159550) inferring that they lie on the same paternal haplotype. Whilst consensus
SNV-calling error rates from ONT data remain substantially higher than those from
short-read methods, we demonstrate the substantial benefits of analytical
innovation. Ongoing improvements to base-calling and SNV-calling methodology must
continue for nanopore sequencing to establish itself as a primary method for
clinical WGS.