Submitted Abstracts from Summer School Participants

2018 Public Health Genomics  
Recipient of an Onassis Foundation scholarship Objectives and Study: Pharmacogenomics aims to rationalize drug use. To date, over 150 drugs have been approved by the US Food and Drug Administration and the European Medicines Agency bearing pharmacogenomics information in their labels. However, no comprehensive lists exist online for clinicians to retrieve the information related to the respective pharmacogenomic biomarkers. Methods: To create such a comprehensive resource, we have extracted and
more » ... curated information from the published literature and online resources. Herein, we selected only those pharmacogenomic biomarkers having strong evidence for their clinical utility. Our repository was further enriched with the existing information documented in the major regulatory bodies, such as the Pharmacogenomics Working Parties of the US Food and Drug Administration and the European Medicines Agency. Results: Our literature mining effort resulted in a total of 370 records, involving correlations between 226 drugs and 95 genes, implicated in drug treatment modalities. From these recommendations, 103 relate to drug toxicity (e.g. adverse drug reactions), 123 are associated with lack of drug efficacy, 45 correspond to both aforementioned cases, while 23 are for information only. Similarities and, most importantly, discrepancies between the regulatory bodies in question were highlighted. Conclusion: Triangulating between drugs, genes and pharmacogenomic biomarkers represents our effort to transform this repository into a comprehensive and dynamically curated online database catalyzing the application of clinical pharmacogenomics. This online tool will stand as the first example of an one-stop solution to assess in real-time the implication of genomic biomarkers in drug response, leading to treatment individualization. Objectives and Study: Precision medicine, genomic and diagnostic services are no longer limited to developed countries. This broadening in geography of biomarker applications and omics diagnostics also demands empirical study of implementation, diagnostic testing, and counselling practices in the field. For example, the Malaysian population has large ethnic diversity and high prevalence of genetic disorders such as hemoglobinopathies and metabolic disorders. Increased morbidity and mortality from such diseases have a direct impact on society and health system sustainability and for this, decision-making becomes of outmost importance. We report here on our findings on the landscape of genomic testing and genetic counselling services in Malaysia. Methods: We first defined the framework of all Malaysian stakeholders that offer genomics services and next, we identified the related information gaps, as depicted through the service providers' online websites. Results: Our research framework revealed that there is a very diverse spectrum of genomics services in Malaysia, in which wetand dry-laboratory services integrate. Moreover, we identify the current gaps and possible remedies to improve the quality of genomic and predictive analytics, not to mention considerations to ensure robust ethics and responsible innovation. To our knowledge, this is the first such study to be performed for a Southeast Asian country. Conclusion: Our genomic medicine services mapping strategy presented in this study may serve as a model for field assessment at regional, national, and international levels as precision medicine is expanding globally and new governance challenges and opportunities continue to emerge for smart implementation science. Objectives and Study: The diversity and interactions of the microbial ecosystem in humans become of prime interest when clinical pharmacogenomics is to be implemented. Despite the advent of technology and the extensive use of next-generation sequencing, information still needs to be translated in knowledge. Results: Publicly available guidelines were reviewed and compared to reach a consensus in terms of the investigated gene-drug pairs, their different level and classification of evidence, which are rated through a scoring system, the recommended therapeutic strategy and the clinical impact of pre-emptive PGx test. Information on the strength of the recommendation (classification of recommendation, level of evidence and clinical impact) were considered necessary to be integrated in the prescribing system along with the therapeutic recommendation. A prototype of a decisionsupport system is being developed through the partnership with two high-tech companies in Italy, which are actively working on the healthcare system computerization. Conclusions: Scientific and clinical expertise in the oncologic pharmacogenomic field were put together, thanks to the coordinated efforts of an established partnership. The pre-emptive pharmacogenomic approach in the clinical practice in Italy was implemented and demonstrated its benefit in both patients' clinical outcome and quality of life, with an economic advantage for the healthcare system. 17 types of interest (Behcet's plus ALS plus spastic paraparesis), c) in neurodegenerative disease phenotypes of interest (amyotrophic lateral sclerosis plus spastic paraparesis) and/ or metabolic disorders (Behcet's disease). In total, 260,671 genomic variants were assessed and SLC22A24 genomic variants were further validated by PCR and Sanger sequencing in ALS patients of Hellenic origin. Results: Our findings demonstrate the existenc e of significant genomic consistency among the disease phenotypes in question, with 12,612 genomic variants being in common. Interestingly, these genomic variants are predominantly found in chromosomes 7, 8 and 11. Moreover, genomic variants unique to ALS and/or spastic paraparesis have been highlighted. Conclusion: Our wet-and dry-lab approach may serve as a paradigm to reveal the "actionable genome" and empower data reliability in multigenic disease phenotypes.
doi:10.1159/000493204 pmid:30219809 fatcat:tby4kmgmp5cabk74tpw77yxjcq