Ari Allyn-Feuer1, Alex Ade1, Jasmine A Luzum2, Gerald A Higgins1, Brian D Athey1,3,4,5. 1. Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA. 2. Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA. 3. Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA. 4. Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI 48109, USA. 5. Michigan Institute for Data Science, University of Michigan Office of Research, Ann Arbor, MI 48109, USA.
Abstract
AIM: 'Pharmacoepigenomics' methods informed by omics datasets and pre-existing knowledge have yielded discoveries in neuropsychiatric pharmacogenomics. Now we evaluate the generality of these methods by discovering an extended warfarin pharmacogenomics pathway. MATERIALS & METHODS: We developed the pharmacoepigenomics informatics pipeline, a scalable multi-omics variant screening pipeline for pharmacogenomics, and conducted an experiment in the genomics of warfarin. RESULTS: We discovered known and novel pharmacogenomics variants and genes, both coding and regulatory, for warfarin response, including adverse events. Such genes and variants cluster in a warfarin response pathway consolidating known and novel warfarin response variants and genes. CONCLUSION: These results can inform a new warfarin test. The pharmacoepigenomics informatics pipeline may be able to discover new pharmacogenomics markers in other drug-disease systems.
AIM: 'Pharmacoepigenomics' methods informed by omics datasets and pre-existing knowledge have yielded discoveries in neuropsychiatric pharmacogenomics. Now we evaluate the generality of these methods by discovering an extended warfarin pharmacogenomics pathway. MATERIALS & METHODS: We developed the pharmacoepigenomics informatics pipeline, a scalable multi-omics variant screening pipeline for pharmacogenomics, and conducted an experiment in the genomics of warfarin. RESULTS: We discovered known and novel pharmacogenomics variants and genes, both coding and regulatory, for warfarin response, including adverse events. Such genes and variants cluster in a warfarin response pathway consolidating known and novel warfarin response variants and genes. CONCLUSION: These results can inform a new warfarin test. The pharmacoepigenomics informatics pipeline may be able to discover new pharmacogenomics markers in other drug-disease systems.
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