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Benchmarking pharmacogenomics genotyping tools: Performance analysis on short-read sequencing samples and depth-dependent evaluation.
- Source :
-
Clinical and translational science [Clin Transl Sci] 2024 Aug; Vol. 17 (8), pp. e13911. - Publication Year :
- 2024
-
Abstract
- Pharmacogenomics (PGx) investigates the influence of genetics on drug responses, enabling tailored treatments for personalized healthcare. This study assessed the accuracy of genotyping six genes using whole genome sequencing with four different computational tools and various sequencing depths. The effects of using different reference genomes (GRCh38 and GRCh37) and sequence aligners (BWA-MEM and Bowtie2) were also explored. The results showed generally minor variations in tool performance across most genes; however, more notable discrepancies were observed in the analysis of the complex CYP2D6 gene. Cyrius, a CYP2D6-specific tool, demonstrated the most robust performance, achieving the highest concordance rates for CYP2D6 in all instances, comparable to the consensus approach in most cases. There were rather small differences between the samples with 20× coverage depth and those with higher depth, but the decreased performance was more evident at lower depths, particularly at 5×. Additionally, variations in CYP2D6 results were observed when samples were aligned to different reference genomes using the same method, or to the same genome using different aligners, which led to reporting incorrect rare star alleles in several cases. These findings inform the selection of optimal PGx tools and methodologies as well as suggest that employing a consensus approach with two or more tools might be preferable for certain genes and tool combinations, especially at lower sequencing depths, to ensure accurate results. Additionally, we show how the upstream alignment can affect the performance of tools, an important factor to take into account.<br /> (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
- Subjects :
- Humans
Cytochrome P-450 CYP2C19 genetics
Whole Genome Sequencing standards
Whole Genome Sequencing methods
Genotyping Techniques methods
Genotype
Cytochrome P-450 CYP2C9 genetics
Cytochrome P-450 CYP2A6 genetics
Pharmacogenomic Testing standards
Pharmacogenomic Testing methods
High-Throughput Nucleotide Sequencing standards
Vitamin K Epoxide Reductases
Benchmarking
Cytochrome P-450 CYP2D6 genetics
Pharmacogenetics standards
Pharmacogenetics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1752-8062
- Volume :
- 17
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Clinical and translational science
- Publication Type :
- Academic Journal
- Accession number :
- 39123290
- Full Text :
- https://doi.org/10.1111/cts.13911