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bioRxiv · 10.1101/2020.05.05.077966

Accurate CYP2D6 genotyping using whole genome sequencing data

Chen, X.·Shen, F.·Gonzaludo, N.·Malhotra, A.·Rogert, C.·Taft, R. J.·Bentley, D. R.·Eberle, M. A.
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Abstract

Responsible for the metabolism of 25% of clinically used drugs, CYP2D6 is a critical component of personalized medicine initiatives. Genotyping CYP2D6 is challenging due to sequence similarity with its pseudogene paralog CYP2D7 and a high number and variety of common structural variants (SVs). Here we describe a novel bioinformatics method, Cyrius, that accurately genotypes CYP2D6 using whole-genome sequencing (WGS) data. We show that Cyrius has superior performance (96.5% concordance with truth genotypes) compared to existing methods (84-86.8%). After implementing the improvements identified from the comparison against the truth data, Cyriuss accuracy has since been improved to 99.3%. Using Cyrius, we built a haplotype frequency database from 2504 ethnically diverse samples and estimate that SV-containing star alleles are more frequent than previously reported. Cyrius will be an important tool to incorporate pharmacogenomics in WGS-based precision medicine initiatives.

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Chen, X., Shen, F., Gonzaludo, N., Malhotra, A., Rogert, C., Taft, R. J., Bentley, D. R., Eberle, M. A.. 2020-05-06. Accurate CYP2D6 genotyping using whole genome sequencing data. https://doi.org/10.1101/2020.05.05.077966

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