Karl Dietrich Hatz
Complete pharmacogenomic profile from exome sequencing
Exome sequencing (ES) is a cornerstone of clinical genetic diagnosis, yet its application in pharmacogenomics remains limited. While some pharmacogenetic variants are detectable by ES, clinically relevant loci such as CYP2D6, UGT1A1, and HLA remain challenging. We present a robust, comprehensive method to derive a complete pharmacogenomic profile directly from standard ES data. Our method addresses primary limitations of ES for pharmacogenomics, including low coverage and structural complexity at critical loci. We analyzed 66 samples from diverse sources, targeting 217 variants across a panel of 23 pharmacogenes. The method was validated by comparing its results with reference samples from the Genetic Testing Reference Material Coordination Program, as well as with the Veridose Core+CNV assay(R) (Agena) and the Personal Medicine Profile assay(R) (GeneTelligence). HLA typing performance was assessed and confirmed through comparison with both the Immucor LIFECODES HLA-SSO kit and a clinical transplantation-grade HLA assay. This validation demonstrates that ES can provide a comprehensive pharmacogenomic profile in a single, streamlined workflow, facilitating seamless integration of pharmacogenomics into precision medicine. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement BC is supported by a grant from INSERM and the French Ministry of Health (Inserm-AAP Messidore 2022-No. 9), and by a French Government grand managed by the Agence Nationale de la Recherche under the France 2030 program, reference ANR22-EXPR0013). AG is supported by a CIFRE fellowship awarded by the French National Association for Research and Technology (ANRT). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board (Direction de la Recherche Clinique et de l'Innovation (APHP220461)) and the Ethics board of Sorbonne Universite (CER-2022-009) gave ethical approval for this work. Written informed consent for participation in the study and publication of related data was obtained from all individuals whose data are included in the manuscript, in accordance with institutional, national, and international regulations. Copies of all consent forms are securely stored and can be made available to the journal or relevant authorities upon request. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymized data that support the findings of this study are available on request from the corresponding author, Laure Raymond. The data are not publicly available due to restrictions, their containing information that could compromise the privacy of research participants.
Rhyothemis
Dora Koller
Muninn 🍃