Stargazer: a software tool for calling star alleles from next-generation sequencing data using CYP2D6 as a model.
CYP2D6 genotyping
next-generation sequencing
pharmacogenomics
star alleles
structural variation
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
12
01
2018
accepted:
23
04
2018
pubmed:
8
6
2018
medline:
13
11
2019
entrez:
8
6
2018
Statut:
ppublish
Résumé
Genotyping CYP2D6 is important for precision drug therapy because the enzyme it encodes metabolizes approximately 25% of drugs, and its activity varies considerably among individuals. Genotype analysis of CYP2D6 is challenging due to its highly polymorphic nature. Over 100 haplotypes (star alleles) have been defined for CYP2D6, some involving a gene conversion with its nearby nonfunctional but highly homologous paralog CYP2D7. We present Stargazer, a new bioinformatics tool that uses next-generation sequencing (NGS) data to call star alleles for CYP2D6 ( https://stargazer.gs.washington.edu/stargazerweb/ ). Stargazer is currently being extended for other pharmacogenes. Stargazer identifies star alleles from NGS data by detecting single nucleotide variants, insertion-deletion variants, and structural variants. Stargazer detects structural variation, including gene deletions, duplications, and conversions, by calculating paralog-specific copy numbers from read depths. We applied Stargazer to the NGS data of 32 ethnically diverse HapMap trios that were genotyped by TaqMan assays, long-range polymerase chain reaction, quantitative multiplex polymerase chain reaction, high-resolution melting analysis, and/or Sanger sequencing. CYP2D6 genotyping by Stargazer was 99.0% concordant with the data obtained by these methods, and showed that 28.1% of the samples had structural variation including CYP2D6/CYP2D7 hybrids. Accurate genotyping of pharmacogenes with NGS and subsequent allele calling with Stargazer will aid the implementation of precision drug therapy.
Identifiants
pubmed: 29875422
doi: 10.1038/s41436-018-0054-0
pii: S1098-3600(21)04621-9
pmc: PMC6281872
mid: NIHMS962794
doi:
Substances chimiques
Cytochrome P-450 CYP2D6
EC 1.14.14.1
Types de publication
Comparative Study
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
361-372Subventions
Organisme : NIGMS NIH HHS
ID : P50 GM115318
Pays : United States
Organisme : NIGMS NIH HHS
ID : R24 GM115277
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007828
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM092676
Pays : United States
Organisme : NHLBI NIH HHS
ID : U19 HL069757
Pays : United States
Organisme : NIH HHS
ID : S10 OD021553
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM116691
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL069757
Pays : United States
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