Pharmacogenomics at the center of precision medicine: challenges and perspective in an era of Big Data.

Pharmacogenomics (PGx) is one of the core elements of personalized medicine. PGx information reduces the likelihood of adverse drug reactions and optimizes therapeutic efficacy. St Catherine Specialty Hospital in Zagreb/Zabok, Croatia has implemented a personalized patient approach using the RightMed® Comprehensive PGx panel of 25 pharmacogenes plus Facor V Leiden, Factor II and MTHFR genes, which is interpreted by a special counseling team to offer the best quality of care. With the advent of significant technological advances comes another challenge: how can we harness the data to inform clinically actionable measures and how can we use it to develop better predictive risk models? We propose to apply the principles artificial intelligence to develop a medication optimization platform to prevent, manage and treat different diseases.

[1]  G. Mazandu,et al.  Implementing Artificial Intelligence and Digital Health in Resource-Limited Settings? Top 10 Lessons We Learned in Congenital Heart Defects and Cardiology. , 2020, Omics : a journal of integrative biology.

[2]  D. Primorac,et al.  Challenges in anesthesia personalization: resolving the pharmacogenomic puzzle. , 2019, Personalized medicine.

[3]  Marcus Woo,et al.  An AI boost for clinical trials , 2019, Nature.

[4]  Tom Nadarzynski,et al.  Acceptability of artificial intelligence (AI)-led chatbot services in healthcare: A mixed-methods study , 2019, Digital health.

[5]  Jianying Hu,et al.  Artificial intelligence and machine learning in clinical development: a translational perspective , 2019, npj Digital Medicine.

[6]  E. Heard,et al.  Advances in epigenetics link genetics to the environment and disease , 2019, Nature.

[7]  Ravishankar K. Iyer,et al.  Pharmacogenomics‐Driven Prediction of Antidepressant Treatment Outcomes: A Machine‐Learning Approach With Multi‐trial Replication , 2019, Clinical pharmacology and therapeutics.

[8]  Phedias Diamandis,et al.  Physician perspectives on integration of artificial intelligence into diagnostic pathology , 2019, npj Digital Medicine.

[9]  K. Sangkuhl,et al.  Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 (CYP)2D6 Genotype and Atomoxetine Therapy , 2019, Clinical pharmacology and therapeutics.

[10]  A. Seyhan,et al.  Are innovation and new technologies in precision medicine paving a new era in patients centric care? , 2019, Journal of Translational Medicine.

[11]  D. Primorac,et al.  Continuing war on pain: a personalized approach to the therapy with nonsteroidal anti-inflammatory drugs and opioids. , 2019, Personalized medicine.

[12]  K. Chung,et al.  Implementing Precision Medicine and Artificial Intelligence in Plastic Surgery: Concepts and Future Prospects , 2019, Plastic and reconstructive surgery. Global open.

[13]  Sephalie Y. Patel,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes , 2019, Clinical pharmacology and therapeutics.

[14]  M. Relling,et al.  Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update , 2019, Clinical pharmacology and therapeutics.

[15]  Eric J Topol,et al.  High-performance medicine: the convergence of human and artificial intelligence , 2019, Nature Medicine.

[16]  Andre Esteva,et al.  A guide to deep learning in healthcare , 2019, Nature Medicine.

[17]  Jie Xu,et al.  The practical implementation of artificial intelligence technologies in medicine , 2019, Nature Medicine.

[18]  P. Kasi,et al.  Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma , 2018, Front. Pharmacol..

[19]  F. Sardanelli,et al.  Artificial intelligence in medical imaging: threat or opportunity? Radiologists again at the forefront of innovation in medicine , 2018, European Radiology Experimental.

[20]  G. Hessler,et al.  Artificial Intelligence in Drug Design , 2018, Molecules.

[21]  Holger Fröhlich,et al.  From hype to reality: data science enabling personalized medicine , 2018, BMC Medicine.

[22]  Ahmed Hosny,et al.  Artificial intelligence in radiology , 2018, Nature Reviews Cancer.

[23]  D. Primorac,et al.  Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives. , 2018, Personalized medicine.

[24]  M. Whirl‐Carrillo,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy , 2018, Clinical pharmacology and therapeutics.

[25]  Julie A. Johnson,et al.  Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine , 2018, Expert opinion on drug metabolism & toxicology.

[26]  M. Whirl‐Carrillo,et al.  Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update , 2018, Clinical pharmacology and therapeutics.

[27]  Julia M. Barbarino,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update , 2018, Clinical pharmacology and therapeutics.

[28]  S. Mohamad R. Soroushmehr,et al.  Deep Learning in Pharmacogenomics: From Gene Regulation to Patient Stratification , 2018, Pharmacogenomics.

[29]  A. Lukowiak,et al.  Estimating cost savings of pharmacogenetic testing for depression in real-world clinical settings , 2018, Neuropsychiatric disease and treatment.

[30]  T. Park,et al.  Analysis of population-specific pharmacogenomic variants using next-generation sequencing data , 2017, Scientific Reports.

[31]  T E Klein,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics‐Guided Warfarin Dosing: 2017 Update , 2017, Clinical pharmacology and therapeutics.

[32]  Rj H Gordon,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron , 2017, Clinical pharmacology and therapeutics.

[33]  Julia M. Barbarino,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy , 2017, Clinical pharmacology and therapeutics.

[34]  K. Sangkuhl,et al.  Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update , 2017, Clinical pharmacology and therapeutics.

[35]  R. Shah Pharmacogenetics and precision medicine: Is inflammation a covert threat to effective genotype-based therapy? , 2017, Therapeutic advances in drug safety.

[36]  Kalpana Raja,et al.  Machine learning workflow to enhance predictions of Adverse Drug Reactions (ADRs) through drug-gene interactions: application to drugs for cutaneous diseases , 2017, Scientific Reports.

[37]  Sivanesan Dakshanamurthy,et al.  Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools. , 2017, Current drug metabolism.

[38]  Laura Shafner,et al.  Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy , 2017, Stroke.

[39]  Demis Hassabis,et al.  Artificial Intelligence: Chess match of the century , 2017, Nature.

[40]  W. Chung,et al.  Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation , 2016, International journal of molecular sciences.

[41]  F. Carvalho,et al.  Comparative metabolism of tramadol and tapentadol: a toxicological perspective , 2016, Drug metabolism reviews.

[42]  M. Weale,et al.  Cost-effectiveness of pharmacogenetic-guided treatment: are we there yet? , 2016, The Pharmacogenomics Journal.

[43]  Muhammad Badruddin Khan,et al.  Machine Learning: Algorithms and Applications , 2016 .

[44]  M. Pirmohamed,et al.  A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions , 2016, PharmacoEconomics.

[45]  S. Vegter,et al.  Economic Evaluations of Pharmacogenetic and Pharmacogenomic Screening Tests: A Systematic Review. Second Update of the Literature , 2016, PloS one.

[46]  Y. Teo,et al.  Genetic diversity of variants involved in drug response and metabolism in Sri Lankan populations: implications for clinical implementation of pharmacogenomics , 2015, Pharmacogenetics and genomics.

[47]  K. Sangkuhl,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors , 2015, Clinical pharmacology and therapeutics.

[48]  Julia M. Barbarino,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing , 2015, Clinical pharmacology and therapeutics.

[49]  Richard Ofori-Asenso,et al.  Perspective: Does personalized medicine hold the future for medicine? , 2015, Journal of pharmacy & bioallied sciences.

[50]  R. Shah,et al.  Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine , 2015, Drug Metabolism and Disposition.

[51]  R. Shah,et al.  Addressing phenoconversion: the Achilles' heel of personalized medicine , 2015, British journal of clinical pharmacology.

[52]  H. Ho,et al.  Metabolism-related pharmacokinetic drug−drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations , 2015, British journal of clinical pharmacology.

[53]  T E Klein,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing , 2014 .

[54]  L Gong,et al.  The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 and Simvastatin‐Induced Myopathy: 2014 Update , 2014, Clinical pharmacology and therapeutics.

[55]  C. Altar,et al.  A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. , 2014, Psychiatric services.

[56]  M. Relling,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Rasburicase Therapy in the Context of G6PD Deficiency Genotype , 2014, Clinical pharmacology and therapeutics.

[57]  E. McDonagh,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Genotype , 2014, Clinical pharmacology and therapeutics.

[58]  T. Klein,et al.  Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update , 2014, Clinical pharmacology and therapy.

[59]  L. Gong,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for IFNL3 (IL28B) Genotype and PEG Interferon‐α–Based Regimens , 2014, Clinical pharmacology and therapy.

[60]  Janet Sultana,et al.  Clinical and economic burden of adverse drug reactions , 2013, Journal of pharmacology & pharmacotherapeutics.

[61]  J. Mega,et al.  Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update , 2013, Clinical pharmacology and therapeutics.

[62]  C. Rotimi,et al.  Pharmacogenomics, ancestry and clinical decision making for global populations , 2013, The Pharmacogenomics Journal.

[63]  Darcy A. Davis,et al.  Bringing Big Data to Personalized Healthcare: A Patient-Centered Framework , 2013, Journal of General Internal Medicine.

[64]  K. Tansey,et al.  Contribution of Common Genetic Variants to Antidepressant Response , 2013, Biological Psychiatry.

[65]  C. Thorn,et al.  Clinical Pharmacogenetics Implementation Consortium Guidelines for Human Leukocyte Antigen‐B Genotype and Allopurinol Dosing , 2013, Clinical pharmacology and therapeutics.

[66]  T. Klein,et al.  Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA‐B Genotype and Abacavir Dosing , 2012, Clinical pharmacology and therapeutics.

[67]  F. Fonseca,et al.  Pharmacokinetic interactions between clopidogrel and rosuvastatin: effects on vascular protection in subjects with coronary heart disease. , 2012, International journal of cardiology.

[68]  L. Hood,et al.  Systems cancer medicine: towards realization of predictive, preventive, personalized and participatory (P4) medicine , 2012, Journal of internal medicine.

[69]  N. Clark,et al.  Alleviating suffering 101--pain relief in the United States. , 2012, The New England journal of medicine.

[70]  Christine W. Duarte,et al.  High-dimensional pharmacogenetic prediction of a continuous trait using machine learning techniques with application to warfarin dose prediction in African Americans , 2011, Bioinform..

[71]  L. Hood,et al.  Predictive, personalized, preventive, participatory (P4) cancer medicine , 2011, Nature Reviews Clinical Oncology.

[72]  G. Novelli,et al.  Personalized genomic medicine , 2010, Internal and emergency medicine.

[73]  Subin Mary Zachariah,et al.  Pharmacogenomics: The Right Drug to the Right Person , 2009, Journal of clinical medicine research.

[74]  E. Antman,et al.  Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials , 2009, The Lancet.

[75]  B. Schackman,et al.  Cost effectiveness of pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 before irinotecan administration for metastatic colorectal cancer , 2009, Cancer.

[76]  M Heath-Chiozzi,et al.  Clinical application of pharmacogenetics. , 2001, Trends in molecular medicine.

[77]  B K Tang,et al.  Hypothesis: comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. , 1998, Pharmacogenetics.

[78]  R. Herings,et al.  Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme , 1995, The Lancet.

[79]  D Servan-Schreiber,et al.  Artificial Intelligence and Psychiatry , 1986, The Journal of nervous and mental disease.

[80]  A. M. Turing,et al.  Computing Machinery and Intelligence , 1950, The Philosophy of Artificial Intelligence.

[81]  Nicholas J Schork,et al.  Artificial Intelligence and Personalized Medicine. , 2019, Cancer treatment and research.

[82]  M. Whirl‐Carrillo,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing , 2016, Clinical pharmacology and therapeutics.

[83]  P. Corey,et al.  Incidence of Adverse Drug Reactions in Hospitalized Patients , 2012 .

[84]  Russ B Altman,et al.  PharmGKB: the Pharmacogenomics Knowledge Base. , 2013, Methods in molecular biology.