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Chiral DNA sequences as commutable controls for clinical genomics
Chirality is a property describing any object that is inequivalent to its mirror image. Due to its 5′–3′ directionality, a DNA sequence is distinct from a mirrored sequence arranged in reverse nucleotide-order, and is therefore chiral. A given sequence and its opposing chiral partner sequence share...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430799/ https://www.ncbi.nlm.nih.gov/pubmed/30902988 http://dx.doi.org/10.1038/s41467-019-09272-0 |
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author | Deveson, Ira W. Madala, Bindu Swapna Blackburn, James Barker, Chris Wong, Ted Barton, Kirston M. Smith, Martin A. Watkins, D. Neil Mercer, Tim R. |
author_facet | Deveson, Ira W. Madala, Bindu Swapna Blackburn, James Barker, Chris Wong, Ted Barton, Kirston M. Smith, Martin A. Watkins, D. Neil Mercer, Tim R. |
author_sort | Deveson, Ira W. |
collection | PubMed |
description | Chirality is a property describing any object that is inequivalent to its mirror image. Due to its 5′–3′ directionality, a DNA sequence is distinct from a mirrored sequence arranged in reverse nucleotide-order, and is therefore chiral. A given sequence and its opposing chiral partner sequence share many properties, such as nucleotide composition and sequence entropy. Here we demonstrate that chiral DNA sequence pairs also perform equivalently during molecular and bioinformatic techniques that underpin genetic analysis, including PCR amplification, hybridization, whole-genome, target-enriched and nanopore sequencing, sequence alignment and variant detection. Given these shared properties, synthetic DNA sequences mirroring clinically relevant or analytically challenging regions of the human genome are ideal controls for clinical genomics. The addition of synthetic chiral sequences (sequins) to patient tumor samples can prevent false-positive and false-negative mutation detection to improve diagnosis. Accordingly, we propose that sequins can fulfill the need for commutable internal controls in precision medicine. |
format | Online Article Text |
id | pubmed-6430799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64307992019-03-25 Chiral DNA sequences as commutable controls for clinical genomics Deveson, Ira W. Madala, Bindu Swapna Blackburn, James Barker, Chris Wong, Ted Barton, Kirston M. Smith, Martin A. Watkins, D. Neil Mercer, Tim R. Nat Commun Article Chirality is a property describing any object that is inequivalent to its mirror image. Due to its 5′–3′ directionality, a DNA sequence is distinct from a mirrored sequence arranged in reverse nucleotide-order, and is therefore chiral. A given sequence and its opposing chiral partner sequence share many properties, such as nucleotide composition and sequence entropy. Here we demonstrate that chiral DNA sequence pairs also perform equivalently during molecular and bioinformatic techniques that underpin genetic analysis, including PCR amplification, hybridization, whole-genome, target-enriched and nanopore sequencing, sequence alignment and variant detection. Given these shared properties, synthetic DNA sequences mirroring clinically relevant or analytically challenging regions of the human genome are ideal controls for clinical genomics. The addition of synthetic chiral sequences (sequins) to patient tumor samples can prevent false-positive and false-negative mutation detection to improve diagnosis. Accordingly, we propose that sequins can fulfill the need for commutable internal controls in precision medicine. Nature Publishing Group UK 2019-03-22 /pmc/articles/PMC6430799/ /pubmed/30902988 http://dx.doi.org/10.1038/s41467-019-09272-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Deveson, Ira W. Madala, Bindu Swapna Blackburn, James Barker, Chris Wong, Ted Barton, Kirston M. Smith, Martin A. Watkins, D. Neil Mercer, Tim R. Chiral DNA sequences as commutable controls for clinical genomics |
title | Chiral DNA sequences as commutable controls for clinical genomics |
title_full | Chiral DNA sequences as commutable controls for clinical genomics |
title_fullStr | Chiral DNA sequences as commutable controls for clinical genomics |
title_full_unstemmed | Chiral DNA sequences as commutable controls for clinical genomics |
title_short | Chiral DNA sequences as commutable controls for clinical genomics |
title_sort | chiral dna sequences as commutable controls for clinical genomics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430799/ https://www.ncbi.nlm.nih.gov/pubmed/30902988 http://dx.doi.org/10.1038/s41467-019-09272-0 |
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