Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long Reads
Summary: One of the remaining challenges to describing an individual's genetic variation lies in the highly heterogeneous and complex genomic regions that impede the use of classical reference-guided mapping and assembly approaches. Once such region is the Immunoglobulin heavy chain locus (IGH)...
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2020-03-01
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doaj-8015ce18506541f8bbcb679a4cc47fda2020-11-25T02:40:45ZengElsevieriScience2589-00422020-03-01233Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long ReadsMichael Ford0Ehsan Haghshenas1Corey T. Watson2S. Cenk Sahinalp3School of Computing Science, Simon Fraser University, Burnaby V5A 1S6, CanadaSchool of Computing Science, Simon Fraser University, Burnaby V5A 1S6, CanadaDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville 40292, USACancer Data Science Laboratory, National Cancer Institute, Bethesda, MD 20892, USA; Corresponding authorSummary: One of the remaining challenges to describing an individual's genetic variation lies in the highly heterogeneous and complex genomic regions that impede the use of classical reference-guided mapping and assembly approaches. Once such region is the Immunoglobulin heavy chain locus (IGH), which is critical for the development of antibodies and the adaptive immune system. We describe ImmunoTyper, the first PacBio-based genotyping and copy number calling tool specifically designed for IGH V genes (IGHV). We demonstrate that ImmunoTyper's multi-stage clustering and combinatorial optimization approach represents the most comprehensive IGHV genotyping approach published to date, through validation using gold-standard IGH reference sequence. This preliminary work establishes the feasibility of fine-grained genotype and copy number analysis using error-prone long reads in complex multi-gene loci and opens the door for in-depth investigation into IGHV heterogeneity using accessible and increasingly common whole-genome sequence. : Biological Sciences; Bioinformatics; Computational Bioinformatics; Genomic Analysis Subject Areas: Biological Sciences, Bioinformatics, Computational Bioinformatics, Genomic Analysishttp://www.sciencedirect.com/science/article/pii/S2589004220300675 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael Ford Ehsan Haghshenas Corey T. Watson S. Cenk Sahinalp |
spellingShingle |
Michael Ford Ehsan Haghshenas Corey T. Watson S. Cenk Sahinalp Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long Reads iScience |
author_facet |
Michael Ford Ehsan Haghshenas Corey T. Watson S. Cenk Sahinalp |
author_sort |
Michael Ford |
title |
Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long Reads |
title_short |
Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long Reads |
title_full |
Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long Reads |
title_fullStr |
Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long Reads |
title_full_unstemmed |
Genotyping and Copy Number Analysis of Immunoglobin Heavy Chain Variable Genes Using Long Reads |
title_sort |
genotyping and copy number analysis of immunoglobin heavy chain variable genes using long reads |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2020-03-01 |
description |
Summary: One of the remaining challenges to describing an individual's genetic variation lies in the highly heterogeneous and complex genomic regions that impede the use of classical reference-guided mapping and assembly approaches. Once such region is the Immunoglobulin heavy chain locus (IGH), which is critical for the development of antibodies and the adaptive immune system. We describe ImmunoTyper, the first PacBio-based genotyping and copy number calling tool specifically designed for IGH V genes (IGHV). We demonstrate that ImmunoTyper's multi-stage clustering and combinatorial optimization approach represents the most comprehensive IGHV genotyping approach published to date, through validation using gold-standard IGH reference sequence. This preliminary work establishes the feasibility of fine-grained genotype and copy number analysis using error-prone long reads in complex multi-gene loci and opens the door for in-depth investigation into IGHV heterogeneity using accessible and increasingly common whole-genome sequence. : Biological Sciences; Bioinformatics; Computational Bioinformatics; Genomic Analysis Subject Areas: Biological Sciences, Bioinformatics, Computational Bioinformatics, Genomic Analysis |
url |
http://www.sciencedirect.com/science/article/pii/S2589004220300675 |
work_keys_str_mv |
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