Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer

The MinION is a bench top sequencer by Oxford nanopore technologies (ONT) that allows long reads of DNA sequence. Few studies have tested whether polymorphisms can be detected using this device. Several polymorphisms within the APP gene were used to test this capability. Library preparation and sequ...

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Main Author: Brookes, Keeley
Format: Article
Published: OMICS International 2016
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Online Access:https://eprints.nottingham.ac.uk/33520/
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author Brookes, Keeley
author_facet Brookes, Keeley
author_sort Brookes, Keeley
building Nottingham Research Data Repository
collection Online Access
description The MinION is a bench top sequencer by Oxford nanopore technologies (ONT) that allows long reads of DNA sequence. Few studies have tested whether polymorphisms can be detected using this device. Several polymorphisms within the APP gene were used to test this capability. Library preparation and sequencing were performed using standard ONT protocols for samples harbouring ive different mutations. Alignments to the reference sequence were analysed in MinoTour and basecalls were manually investigated using proportion of reference calls between samples to identify the variants. MinoTour’s algorithm for variant detection was unable to identify the polymorphisms due to high base calling error rate. By calculating the difference in reference basecall proportions along the amplicon, it was possible to identify the polymorphisms above a Bonferroni-corrected threshold (p<1 × 10-4). The MinION has potential for polymorphism detection when comparing samples; however careful interpretation is needed as high base calling error rates can mask the presence of polymorphisms.
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spelling nottingham-335202024-08-15T15:19:15Z https://eprints.nottingham.ac.uk/33520/ Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer Brookes, Keeley The MinION is a bench top sequencer by Oxford nanopore technologies (ONT) that allows long reads of DNA sequence. Few studies have tested whether polymorphisms can be detected using this device. Several polymorphisms within the APP gene were used to test this capability. Library preparation and sequencing were performed using standard ONT protocols for samples harbouring ive different mutations. Alignments to the reference sequence were analysed in MinoTour and basecalls were manually investigated using proportion of reference calls between samples to identify the variants. MinoTour’s algorithm for variant detection was unable to identify the polymorphisms due to high base calling error rate. By calculating the difference in reference basecall proportions along the amplicon, it was possible to identify the polymorphisms above a Bonferroni-corrected threshold (p<1 × 10-4). The MinION has potential for polymorphism detection when comparing samples; however careful interpretation is needed as high base calling error rates can mask the presence of polymorphisms. OMICS International 2016-05-13 Article PeerReviewed Brookes, Keeley (2016) Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer. Journal of Next Generation Sequencing & Applications, 3 (1). ISSN 2469-9853 Nanopore technology; MinION; Sequencing; Polymorphism detection; Deletion doi:10.4172/jngsa.1000125 doi:10.4172/jngsa.1000125
spellingShingle Nanopore technology; MinION; Sequencing; Polymorphism detection; Deletion
Brookes, Keeley
Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer
title Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer
title_full Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer
title_fullStr Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer
title_full_unstemmed Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer
title_short Identifying polymorphisms in the Alzheimer's related APP gene using the MinION sequencer
title_sort identifying polymorphisms in the alzheimer's related app gene using the minion sequencer
topic Nanopore technology; MinION; Sequencing; Polymorphism detection; Deletion
url https://eprints.nottingham.ac.uk/33520/
https://eprints.nottingham.ac.uk/33520/