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The 10 th biannual conference on Systems Medicine, Personalised Health and Therapy, under the auspices of the Santorini Conferences Association (SCs), the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), the Hellenic Society of Pharmacogenomics and personalized Diagnosis and Therapy (EEPHARM), and the European Society of Pharmacogenomics and Personalised Therapy (ESPT), took place in Santorini, Greece, between 23-26 of May 2022. It was sponsored by several companies: Randox (Crumlin, United Kingdom), Agena Bioscience (Hamburg, Germany) and Cellecta as Gold Sponsors; Thermofisher Scientific (San Francisco, United States) and PharmGenetix (Vienna, Austria), as Silver Sponsors; HMG systems Engineering (Fuerth, Germany) as Bronze Sponsors, reinforced by specific supports from the Santorini Conferences Association (SCs), The Austrian Society for Laboratory Medicine & Clinical Chemistry (OGLMKC), Transgene (Strasbourg, France), The Journal "Frontiers in Genetics" and strengthened with scientific meetings supported by the University of Lorraine and INSERM ('Cercle Gutenberg'). In this article we briefly outline the presentations delivered during the conference and review the key messages and conclusions.The conference was officially initiated by Sofia Siest, the President of the Santorini Conference series, thanked all the members of the different committees and the sponsors. She presented an overview of the outcomes of the previous conference and announced the inauguration of the Santorini Conferences series under the umbrella of the Santorini Conferences Association (SCs) and the development of the new website: www.santoriniconference.org. She then underlined that this was the 20 th Anniversary of the conference's series and outlined the content of the scientific program (presentations and speakers) and the different topics to be covered. Following the welcome session, Raute Sunder-Plassmann (Vienna, Austria) and Markus Paulmichl (Salzburg, Austria) introduced the keynote round table, supported by the Austrian Society for Laboratory Medicine & Clinical Chemistry "OGLMKC" and focused on Pharmacogenetics (PGx) Analysis in the Medical Diagnostic Laboratory -From Science to Clinical Decision Support (CDS). The major topics/highlights of the round table discussion included: • Whole genome sequencing provides opportunities to identify new genetic factors for efficacy and safety phenotypes or for explaining the missing phenotype heritability seen in twin studies. New genetic variants could act as regulators of pharmacogenes expression • Long read sequencing allows to unravel complex gene loci • Large biobanks offer the opportunity to discover pharmacogenomic phenotypes • Value in expanding pharmacogenomic research to diverse ancestry groups • Significance of personalized prescription • Advances in genotyping technologies and a concomitant drop in the costs and turnaround time facilitate multi-gene analyses and preemptive pharmacogenetic testing in medical diagnostic laboratories • Value in switching to extended PGx panel diagnostics • Adhere to current guidelines on pharmacogenomic testing and reporting • Importance of recommendations for standardization of pharmacogenetic terminology and test design • Importance of providing clear, concise, and interpretable reports, providing details on the test itself and the identified variants in a separate supplementary document • Need for integrating PGx data into the patient's electronic health record and -if availablein a Clinical Decision Support System (CDSS).M. Ingelmann Sundberg (Stockholm, Sweden) described how the ability to interrogate the whole genome provides us with unparalleled opportunities to identify new genetic predisposing factors in an unbiased manner for both efficacy and safety phenotypes, often leading to new insights into gene function and explaining the missing heritability seen in twin studies. Rare variants, which are unaccounted for during standard genotyping, actually explain up to 4-6 % of the variability in certain genes encoding enzymes and transporters. Similarly, haplotypes in linkage equilibrium to variants defining a specific CYP allele may cause altered CYP activity due to additional variants affecting gene expression. Additionally, variants in genes not directly linked to the ADME gene in question may influence its regulation, as recently demonstrated for the nuclear factor 1B (NFIB)-dependent regulation of CYP2D6 expression and risperidone metabolism in psychiatric patients. Long read sequencing technologies allow to unravel complex gene loci such as the CYD2D locus. M. Pirmohammed (Liverpool, UK) explained how the availability of large-scale biobanks, such as the UK biobank, enables us to identify novel pharmacogenomic phenotypes -but may be limited by the depth of clinical phenotypes within the biobanks. Additionally, it is important to expand pharmacogenomic research to different ethnic groups to ensure that what we discover and implement is relevant to all population and that we do not exacerbate race and health inequalities.Ron HN van Schaik (Rotterdam, The Netherlands) presented how selected centers reported good results for improving medication safety and efficacy by including common genetic variations in genes encoding enzymes, transporters and targets into pharmacogenetic guided treatment decisions. However, comprehensive and/or preemptive pharmacogenetic analyses and their implementation into daily clinical practice is still not very common. Physicians usually rely on reactively ordered PGx tests for selected variants in a single or only a few genes and particularly on a short turnaround time to initiate, adjust or change a standard therapeutic regime. Due to recent advances in genotyping technologies and a concomitant drop in the costs and turnaround time for multi-gene analyses, PGx panel diagnostics using single-nucleotide polymorphism (SNP) genotyping arrays or next-generation sequencing (NGS) based approaches are established in a few medical diagnostic laboratories. But further efforts of wider implementation to the entire healthcare systems is needed. There is also a patient driven demand for PGx guided treatment decisions and multigene/multivariant testing. Preemptive genotyping would ensure that the appropriate genetic information to guide drug therapy is already available when needed and will maximize the effect of PGx. R. Sunder-Plassmann (Vienna, Austria) described how the availability of an abundance of PGx data still represents a huge challenge for physicians, who frequently struggle with the interpretation and application of PGx test results. Hence, PGx reports have to be designed in such a way that the data is easy to comprehend, and the focus is on the current medication and relevant actionable genetic variants, preferentially in a separate short report for immediate use.In addition, a comprehensive report explaining the patient's pharmacogenetic profile in more detail should be also provided. According to current recommendations (ACMG), the patient's genotype, predicted PGx-phenotypes, commonly used drugs that may be affected by the identified genotype, a statement that alternative medication might be considered (if applicable)and resources for guidelines should be reported. Additionally, they suggest reminding physicians that the accuracy of the anticipated PGx phenotype is dependent on the variants identified and that co-medication and drug-drug interactions may also influence the phenotype. For future therapeutic decisions, PGx data should be included in the patients' electronic health records. Currently, only few in vitro diagnostic tests are commercially available for PGx analyses. The majority of medical diagnostic laboratories that offer PGx panel diagnostics use lab developed assays, which may vary in gene selection, variants detected, and nomenclature for phenotype description. This may lead to discrepancies in the test results between laboratories and the need for standardizing the minimal requirements for a diagnostic PGx test. Markus Paulmichl (Salzburg, Austria) closed the session with a presentation on "Standardization in PGx diagnostics".George Dagher (Paris, France) and Sofia Siest (Nancy, France) introduced the keynote lecture on "Advances in Cancer Detection" presented by Nickolas Papadopoulos (Baltimore, United States). Nickolas Papadopoulos highlighted that the earlier a cancer is detected the higher the chance for a successful outcome. For many cancers there are not any screening modalities available. The ability to identify cancers through blood testing is one of the most exciting advances in cancer diagnostics. In a screening setting it provides the opportunity to detect multiple cancer types with a single test. Liquid biopsy also has the potential to detect early signs of minimal residual disease and recurrence. The presentation outlined these opportunities along with challenges associated with such clinical applications. We discussed the biomarkers, technologies and the type of studies required to develop and evaluate the utility of such tests, in the first session of the next conference day.The session was chaired by Georges Weryha, Nancy, France and Georges Dagher, Paris, France and sponsored by AGENA.Klaus Pantel (Hamburg, Germany) started the session with a talk on "Liquid Biopsy: From Discovery to Clinical Implementation", highlighting the utility of liquid biopsy in clinical practice. 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