FixItFelix: improving genomic analysis by fixing reference errors

The current version of the human reference genome, GRCh38, contains a number of errors including 1.2 Mbp of falsely duplicated and 8.04 Mbp of collapsed regions. These errors impact the variant calling of 33 protein-coding genes, including 12 with medical relevance. Here, we present FixItFelix, an e...

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Autores principales: Behera, Sairam, LeFaive, Jonathon, Orchard, Peter, Mahmoud, Medhat, Paulin, Luis F., Farek, Jesse, Soto, Daniela C., Parker, Stephen C. J., Smith, Albert V., Dennis, Megan Y., Zook, Justin M., Sedlazeck, Fritz J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942314/
https://www.ncbi.nlm.nih.gov/pubmed/36810122
http://dx.doi.org/10.1186/s13059-023-02863-7
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author Behera, Sairam
LeFaive, Jonathon
Orchard, Peter
Mahmoud, Medhat
Paulin, Luis F.
Farek, Jesse
Soto, Daniela C.
Parker, Stephen C. J.
Smith, Albert V.
Dennis, Megan Y.
Zook, Justin M.
Sedlazeck, Fritz J.
author_facet Behera, Sairam
LeFaive, Jonathon
Orchard, Peter
Mahmoud, Medhat
Paulin, Luis F.
Farek, Jesse
Soto, Daniela C.
Parker, Stephen C. J.
Smith, Albert V.
Dennis, Megan Y.
Zook, Justin M.
Sedlazeck, Fritz J.
author_sort Behera, Sairam
collection PubMed
description The current version of the human reference genome, GRCh38, contains a number of errors including 1.2 Mbp of falsely duplicated and 8.04 Mbp of collapsed regions. These errors impact the variant calling of 33 protein-coding genes, including 12 with medical relevance. Here, we present FixItFelix, an efficient remapping approach, together with a modified version of the GRCh38 reference genome that improves the subsequent analysis across these genes within minutes for an existing alignment file while maintaining the same coordinates. We showcase these improvements over multi-ethnic control samples, demonstrating improvements for population variant calling as well as eQTL studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-023-02863-7.
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spelling pubmed-99423142023-02-22 FixItFelix: improving genomic analysis by fixing reference errors Behera, Sairam LeFaive, Jonathon Orchard, Peter Mahmoud, Medhat Paulin, Luis F. Farek, Jesse Soto, Daniela C. Parker, Stephen C. J. Smith, Albert V. Dennis, Megan Y. Zook, Justin M. Sedlazeck, Fritz J. Genome Biol Method The current version of the human reference genome, GRCh38, contains a number of errors including 1.2 Mbp of falsely duplicated and 8.04 Mbp of collapsed regions. These errors impact the variant calling of 33 protein-coding genes, including 12 with medical relevance. Here, we present FixItFelix, an efficient remapping approach, together with a modified version of the GRCh38 reference genome that improves the subsequent analysis across these genes within minutes for an existing alignment file while maintaining the same coordinates. We showcase these improvements over multi-ethnic control samples, demonstrating improvements for population variant calling as well as eQTL studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-023-02863-7. BioMed Central 2023-02-21 /pmc/articles/PMC9942314/ /pubmed/36810122 http://dx.doi.org/10.1186/s13059-023-02863-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Method
Behera, Sairam
LeFaive, Jonathon
Orchard, Peter
Mahmoud, Medhat
Paulin, Luis F.
Farek, Jesse
Soto, Daniela C.
Parker, Stephen C. J.
Smith, Albert V.
Dennis, Megan Y.
Zook, Justin M.
Sedlazeck, Fritz J.
FixItFelix: improving genomic analysis by fixing reference errors
title FixItFelix: improving genomic analysis by fixing reference errors
title_full FixItFelix: improving genomic analysis by fixing reference errors
title_fullStr FixItFelix: improving genomic analysis by fixing reference errors
title_full_unstemmed FixItFelix: improving genomic analysis by fixing reference errors
title_short FixItFelix: improving genomic analysis by fixing reference errors
title_sort fixitfelix: improving genomic analysis by fixing reference errors
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942314/
https://www.ncbi.nlm.nih.gov/pubmed/36810122
http://dx.doi.org/10.1186/s13059-023-02863-7
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