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Whole-genome haplotyping using long reads and statistical methods

Rapid growth of sequencing technologies has greatly contributed to increasing our understanding of human genetics. Yet, in spite of this growth, mainstream technologies have been largely unsuccessful in resolving the diploid nature of the human genome. Here we describe statistically aided long read...

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Autores principales: Kuleshov, Volodymyr, Xie, Dan, Chen, Rui, Pushkarev, Dmitry, Ma, Zhihai, Blauwkamp, Tim, Kertesz, Michael, Snyder, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073643/
https://www.ncbi.nlm.nih.gov/pubmed/24561555
http://dx.doi.org/10.1038/nbt.2833
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author Kuleshov, Volodymyr
Xie, Dan
Chen, Rui
Pushkarev, Dmitry
Ma, Zhihai
Blauwkamp, Tim
Kertesz, Michael
Snyder, Michael
author_facet Kuleshov, Volodymyr
Xie, Dan
Chen, Rui
Pushkarev, Dmitry
Ma, Zhihai
Blauwkamp, Tim
Kertesz, Michael
Snyder, Michael
author_sort Kuleshov, Volodymyr
collection PubMed
description Rapid growth of sequencing technologies has greatly contributed to increasing our understanding of human genetics. Yet, in spite of this growth, mainstream technologies have been largely unsuccessful in resolving the diploid nature of the human genome. Here we describe statistically aided long read haplotyping (SLRH), a rapid, accurate method based on a simple experimental protocol that requires potentially as little as 30 Gbp of sequencing in addition to a standard (50x coverage) whole-genome analysis for human samples. Using this technology, we phase 99% of single-nucleotide variants in three human genomes into long haplotype blocks of 200 kbp to 1 Mbp in length. As a demonstration of the potential applications of our method, we determine allele-specific methylation patterns in a human genome and identify hundreds of differentially methylated regions that were previously unknown. Such information may offer insight into the mechanisms behind differential gene expression.
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spelling pubmed-40736432014-09-01 Whole-genome haplotyping using long reads and statistical methods Kuleshov, Volodymyr Xie, Dan Chen, Rui Pushkarev, Dmitry Ma, Zhihai Blauwkamp, Tim Kertesz, Michael Snyder, Michael Nat Biotechnol Article Rapid growth of sequencing technologies has greatly contributed to increasing our understanding of human genetics. Yet, in spite of this growth, mainstream technologies have been largely unsuccessful in resolving the diploid nature of the human genome. Here we describe statistically aided long read haplotyping (SLRH), a rapid, accurate method based on a simple experimental protocol that requires potentially as little as 30 Gbp of sequencing in addition to a standard (50x coverage) whole-genome analysis for human samples. Using this technology, we phase 99% of single-nucleotide variants in three human genomes into long haplotype blocks of 200 kbp to 1 Mbp in length. As a demonstration of the potential applications of our method, we determine allele-specific methylation patterns in a human genome and identify hundreds of differentially methylated regions that were previously unknown. Such information may offer insight into the mechanisms behind differential gene expression. 2014-02-23 2014-03 /pmc/articles/PMC4073643/ /pubmed/24561555 http://dx.doi.org/10.1038/nbt.2833 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kuleshov, Volodymyr
Xie, Dan
Chen, Rui
Pushkarev, Dmitry
Ma, Zhihai
Blauwkamp, Tim
Kertesz, Michael
Snyder, Michael
Whole-genome haplotyping using long reads and statistical methods
title Whole-genome haplotyping using long reads and statistical methods
title_full Whole-genome haplotyping using long reads and statistical methods
title_fullStr Whole-genome haplotyping using long reads and statistical methods
title_full_unstemmed Whole-genome haplotyping using long reads and statistical methods
title_short Whole-genome haplotyping using long reads and statistical methods
title_sort whole-genome haplotyping using long reads and statistical methods
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073643/
https://www.ncbi.nlm.nih.gov/pubmed/24561555
http://dx.doi.org/10.1038/nbt.2833
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