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Haplosaurus computes protein haplotypes for use in precision drug design

Selecting the most appropriate protein sequences is critical for precision drug design. Here we describe Haplosaurus, a bioinformatic tool for computation of protein haplotypes. Haplosaurus computes protein haplotypes from pre-existing chromosomally-phased genomic variation data. Integration into th...

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Autores principales: Spooner, William, McLaren, William, Slidel, Timothy, Finch, Donna K., Butler, Robin, Campbell, Jamie, Eghobamien, Laura, Rider, David, Kiefer, Christine Mione, Robinson, Matthew J., Hardman, Colin, Cunningham, Fiona, Vaughan, Tristan, Flicek, Paul, Huntington, Catherine Chaillan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175845/
https://www.ncbi.nlm.nih.gov/pubmed/30297836
http://dx.doi.org/10.1038/s41467-018-06542-1
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author Spooner, William
McLaren, William
Slidel, Timothy
Finch, Donna K.
Butler, Robin
Campbell, Jamie
Eghobamien, Laura
Rider, David
Kiefer, Christine Mione
Robinson, Matthew J.
Hardman, Colin
Cunningham, Fiona
Vaughan, Tristan
Flicek, Paul
Huntington, Catherine Chaillan
author_facet Spooner, William
McLaren, William
Slidel, Timothy
Finch, Donna K.
Butler, Robin
Campbell, Jamie
Eghobamien, Laura
Rider, David
Kiefer, Christine Mione
Robinson, Matthew J.
Hardman, Colin
Cunningham, Fiona
Vaughan, Tristan
Flicek, Paul
Huntington, Catherine Chaillan
author_sort Spooner, William
collection PubMed
description Selecting the most appropriate protein sequences is critical for precision drug design. Here we describe Haplosaurus, a bioinformatic tool for computation of protein haplotypes. Haplosaurus computes protein haplotypes from pre-existing chromosomally-phased genomic variation data. Integration into the Ensembl resource provides rapid and detailed protein haplotypes retrieval. Using Haplosaurus, we build a database of unique protein haplotypes from the 1000 Genomes dataset reflecting real-world protein sequence variability and their prevalence. For one in seven genes, their most common protein haplotype differs from the reference sequence and a similar number differs on their most common haplotype between human populations. Three case studies show how knowledge of the range of commonly encountered protein forms predicted in populations leads to insights into therapeutic efficacy. Haplosaurus and its associated database is expected to find broad applications in many disciplines using protein sequences and particularly impactful for therapeutics design.
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spelling pubmed-61758452018-10-11 Haplosaurus computes protein haplotypes for use in precision drug design Spooner, William McLaren, William Slidel, Timothy Finch, Donna K. Butler, Robin Campbell, Jamie Eghobamien, Laura Rider, David Kiefer, Christine Mione Robinson, Matthew J. Hardman, Colin Cunningham, Fiona Vaughan, Tristan Flicek, Paul Huntington, Catherine Chaillan Nat Commun Article Selecting the most appropriate protein sequences is critical for precision drug design. Here we describe Haplosaurus, a bioinformatic tool for computation of protein haplotypes. Haplosaurus computes protein haplotypes from pre-existing chromosomally-phased genomic variation data. Integration into the Ensembl resource provides rapid and detailed protein haplotypes retrieval. Using Haplosaurus, we build a database of unique protein haplotypes from the 1000 Genomes dataset reflecting real-world protein sequence variability and their prevalence. For one in seven genes, their most common protein haplotype differs from the reference sequence and a similar number differs on their most common haplotype between human populations. Three case studies show how knowledge of the range of commonly encountered protein forms predicted in populations leads to insights into therapeutic efficacy. Haplosaurus and its associated database is expected to find broad applications in many disciplines using protein sequences and particularly impactful for therapeutics design. Nature Publishing Group UK 2018-10-08 /pmc/articles/PMC6175845/ /pubmed/30297836 http://dx.doi.org/10.1038/s41467-018-06542-1 Text en © The Author(s) 2018 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
Spooner, William
McLaren, William
Slidel, Timothy
Finch, Donna K.
Butler, Robin
Campbell, Jamie
Eghobamien, Laura
Rider, David
Kiefer, Christine Mione
Robinson, Matthew J.
Hardman, Colin
Cunningham, Fiona
Vaughan, Tristan
Flicek, Paul
Huntington, Catherine Chaillan
Haplosaurus computes protein haplotypes for use in precision drug design
title Haplosaurus computes protein haplotypes for use in precision drug design
title_full Haplosaurus computes protein haplotypes for use in precision drug design
title_fullStr Haplosaurus computes protein haplotypes for use in precision drug design
title_full_unstemmed Haplosaurus computes protein haplotypes for use in precision drug design
title_short Haplosaurus computes protein haplotypes for use in precision drug design
title_sort haplosaurus computes protein haplotypes for use in precision drug design
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175845/
https://www.ncbi.nlm.nih.gov/pubmed/30297836
http://dx.doi.org/10.1038/s41467-018-06542-1
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