Team:Patras/Poster
Poster
Team
Authors and Affiliated Institutions
Abstract
Pharmacogenomics is rapidly assuming an integral part of modern health care. Still, its broad applicability relies on the feasibility of performing pharmacogenomic testing in all clinical settings, including in remote areas or resource-limited settings with budget restrictions.
In our project, Hippocrates, we developed a diagnostic tool that aims to introduce the Pharmacogenomics into clinical practice. We present the development of rapid and reliable pharmacogenomics assays using a portable molecular laboratory, namely BentoLab, in the size of a hand-luggage combined with Artificial Intelligence. More specifically, we demonstrate that the genomic analysis of the rs4149056, located within the gene SLCO1B1, can be performed with accuracy on this device. To prove its reliability, all the samples were genotyped using a) the KASP assays referred to as the gold standard and b) using a conventional laboratory equipment. Taking into account the compact size of BentoLab, which directly and positively impacts its portability, and the high accuracy achieved, we conclude that the BentoLab-based genotyping method is warranted for further studies in clinical practices at remote areas and resource-limited as well as time-constrained planetary health settings.
The Artificial Intelligence was used to upgrade the BentoLab and assist the user by directly translating the genetic analysis results into dosing recommendation. The system was established by locating and classifying different objects of interest (OoI) in images of the electrophoresis gels. To perform multiple object detection, a modification of the algorithm Yolo is implemented.
To conclude, the BentoLab-AI system makes Pharmacogenomics’ implementation into clinical practice more accessible than ever before. Through this, personalized medicine can be achieved even by health professionals who have never performed genetic analysis.
Inspiration
Introduction
Problem
Idea
Solution
Wet Lab
Dry Lab
Wet Lab Results
Dry Lab Results
Proof of Concept
Future Directions
Human Practices
References
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2. Redmon, Joseph, Farhadi and Ali, "YOLO9000: Better, Faster, Stronger," arXiv preprint arXiv:1612.08242, 2016
3. Ahrberg CD, Ilic BR, Manz A, and Neuzˇil P. (2016). Handheld real-time PCR device. Lab Chip 16, 586–592.
4. Brunham LR, Baker S, Mammen A, et al. (2018). Role of genetics in the prediction of statin-associated muscle symptoms and optimization of statin use and adherence. Cardiovasc Res 114, 1073–1081.
5. Jangam SR, Agarwal AK, Sur K, and Kelso DM. (2013). A point-of-care PCR test for HIV-1 detection in resourcelimitedsettings. Biosens Bioelectron 42, 69–75.
6. Khine H, Yuet WC, Adams-Huet B, and Ahmad Z. (2016). Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia. Am Heart J 179, 1–9.
7. Koutsilieri S, Tzioufa F, Sismanoglou DC, et al. (2020). Unveiling the guidance heterogeneity for genome-informed drug treatment interventions among regulatory bodies and research consortia. Pharmacol Res 153, 104590.
8. Kurosaki Y, Magassouba N, Oloniniyi OK, et al. (2016). Development and evaluation of reverse transcription-loop6 PSARIAS ET AL. Downloaded by Universiteit Utrecht from www.liebertpub.com at 10/22/20. For personal use only. mediated isothermal amplification (RT-LAMP) assay coupled with a portable device for rapid diagnosis of Ebola virus disease in Guinea. PLoS Negl Trop Dis 10, e0004472.
9. Lim S, Nan H, Lee M, and Kang SH. (2014). Fast on-site diagnosis of influenza A virus by Palm PCR and portable capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci 963, 134–139.
10. Macleod JA, Nemeth AC, Dicke WC, et al. (2016). Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection. Lab Chip 16, 2513–2520.
11. Marx V. (2015). PCR heads into the field. Nat Methods 12, 393–397.
12. McDonagh EM, Thorn CF, Bautista JM, et al. (2012). PharmGKB summary: Very important pharmacogene information for G6PD. Pharmacogenet Genomics 22, 219.
13. Meade T, Sleight P, Collins R, et al. (2008). SLCO1B1 variants and statin-induced myopathy—A genomewide study. N Engl J Med 359, 789–799.
14. Menounos P, Zervas C, Garinis G, et al. (2000). Molecular heterogeneity of the glucose-6-phosphate dehydrogenase deficiency in the Hellenic population. Hum Hered 50, 237–241.
15. Nair CB, Manjula J, Subramani PA, et al. (2016). Differential diagnosis of malaria on truelab Uno, a portable, real-time, MicroPCR device for point-of-care applications. PLoS One 11, e0146961.
16. Pasanen MK, Fredrikson H, Neuvonen PJ, and Niemi M. (2007). Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther 82, 726–733.
17. Pasanen MK, Neuvonen M, Neuvonen PJ, and Niemi M. (2006). SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet Genomics 16, 873–879.
18. Pirmohamed M. (2001). Pharmacogenetics and pharmacogenomics. Br J Clin Pharmacol 52, 345–347.
19. Relling MV, Mcdonagh EM, Chang T, et al. (2014). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clin Pharmacol Ther 96, 169–174.
20. Siamoglou S, Karamperis K, Mitropoulou C, and Patrinos GP. (2020). Costing methods as a means to measure the costs of pharmacogenomics testing. J Appl Lab Med 5, 1005–1016.
21. Siamoglou S, and Patrinos GP. (2019). 2MoBiL laboratory in educational activities in the field of molecular genetics and Personalised Medicine [in Greek]. EnasolijetlAmg Iasqija 1, 17–25.
22. Stroes ES, Thompson PD, Corsini A, et al. (2015). Statin-associated muscle symptoms: Impact on statin therapy—European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. Eur Heart J 36, 1012–1022.
23. Teama S. (2018). DNA polymorphisms: DNA-based molecular markers and their application in medicine. Genetic Diversity and Disease Susceptibility, 25. DOI: 10.5772/intechopen .79517.
24. Thorn CF, Klein TE, and Altman RB. (2013). PharmGKB: The pharmacogenomics knowledge base. Methods Mol Biol 1015, 311–320.
25. Tuteja S, and Rader DJ. (2018). SLCO1B1 and statin therapy: Getting the GIST of pharmacogenetic testing. Circ Genomic Precis Med 11, e002320.
26. Visser BJ, Meerveld-Gerrits J, Kroon D, et al. (2015). Assessing the quality of anti-malarial drugs from Gabonese pharmacies using the MiniLab: A field study. Malar J 14, 1–13.
27. Wang H, Zhang X, Xu X, et al. (2017). A portable microfluidic platform for rapid molecular diagnostic testing of patients with myeloproliferative neoplasms. Sci Rep 7, 1–11.
28. Wilke RA, Ramsey LB, Johnson SG, et al. (2012). The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin Pharmacol Ther 92, 112–117.
29. Zaky WI, Tomaino FR, Pilotte N, et al. (2018). Backpack PCR: A point-of-collection diagnostic platform for the rapid detection of Brugia parasites in mosquitoes. PLoS Negl Trop Dis 12, e0006962.
2. Redmon, Joseph, Farhadi and Ali, "YOLO9000: Better, Faster, Stronger," arXiv preprint arXiv:1612.08242, 2016
3. Ahrberg CD, Ilic BR, Manz A, and Neuzˇil P. (2016). Handheld real-time PCR device. Lab Chip 16, 586–592.
4. Brunham LR, Baker S, Mammen A, et al. (2018). Role of genetics in the prediction of statin-associated muscle symptoms and optimization of statin use and adherence. Cardiovasc Res 114, 1073–1081.
5. Jangam SR, Agarwal AK, Sur K, and Kelso DM. (2013). A point-of-care PCR test for HIV-1 detection in resourcelimitedsettings. Biosens Bioelectron 42, 69–75.
6. Khine H, Yuet WC, Adams-Huet B, and Ahmad Z. (2016). Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia. Am Heart J 179, 1–9.
7. Koutsilieri S, Tzioufa F, Sismanoglou DC, et al. (2020). Unveiling the guidance heterogeneity for genome-informed drug treatment interventions among regulatory bodies and research consortia. Pharmacol Res 153, 104590.
8. Kurosaki Y, Magassouba N, Oloniniyi OK, et al. (2016). Development and evaluation of reverse transcription-loop6 PSARIAS ET AL. Downloaded by Universiteit Utrecht from www.liebertpub.com at 10/22/20. For personal use only. mediated isothermal amplification (RT-LAMP) assay coupled with a portable device for rapid diagnosis of Ebola virus disease in Guinea. PLoS Negl Trop Dis 10, e0004472.
9. Lim S, Nan H, Lee M, and Kang SH. (2014). Fast on-site diagnosis of influenza A virus by Palm PCR and portable capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci 963, 134–139.
10. Macleod JA, Nemeth AC, Dicke WC, et al. (2016). Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection. Lab Chip 16, 2513–2520.
11. Marx V. (2015). PCR heads into the field. Nat Methods 12, 393–397.
12. McDonagh EM, Thorn CF, Bautista JM, et al. (2012). PharmGKB summary: Very important pharmacogene information for G6PD. Pharmacogenet Genomics 22, 219.
13. Meade T, Sleight P, Collins R, et al. (2008). SLCO1B1 variants and statin-induced myopathy—A genomewide study. N Engl J Med 359, 789–799.
14. Menounos P, Zervas C, Garinis G, et al. (2000). Molecular heterogeneity of the glucose-6-phosphate dehydrogenase deficiency in the Hellenic population. Hum Hered 50, 237–241.
15. Nair CB, Manjula J, Subramani PA, et al. (2016). Differential diagnosis of malaria on truelab Uno, a portable, real-time, MicroPCR device for point-of-care applications. PLoS One 11, e0146961.
16. Pasanen MK, Fredrikson H, Neuvonen PJ, and Niemi M. (2007). Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther 82, 726–733.
17. Pasanen MK, Neuvonen M, Neuvonen PJ, and Niemi M. (2006). SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet Genomics 16, 873–879.
18. Pirmohamed M. (2001). Pharmacogenetics and pharmacogenomics. Br J Clin Pharmacol 52, 345–347.
19. Relling MV, Mcdonagh EM, Chang T, et al. (2014). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clin Pharmacol Ther 96, 169–174.
20. Siamoglou S, Karamperis K, Mitropoulou C, and Patrinos GP. (2020). Costing methods as a means to measure the costs of pharmacogenomics testing. J Appl Lab Med 5, 1005–1016.
21. Siamoglou S, and Patrinos GP. (2019). 2MoBiL laboratory in educational activities in the field of molecular genetics and Personalised Medicine [in Greek]. EnasolijetlAmg Iasqija 1, 17–25.
22. Stroes ES, Thompson PD, Corsini A, et al. (2015). Statin-associated muscle symptoms: Impact on statin therapy—European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. Eur Heart J 36, 1012–1022.
23. Teama S. (2018). DNA polymorphisms: DNA-based molecular markers and their application in medicine. Genetic Diversity and Disease Susceptibility, 25. DOI: 10.5772/intechopen .79517.
24. Thorn CF, Klein TE, and Altman RB. (2013). PharmGKB: The pharmacogenomics knowledge base. Methods Mol Biol 1015, 311–320.
25. Tuteja S, and Rader DJ. (2018). SLCO1B1 and statin therapy: Getting the GIST of pharmacogenetic testing. Circ Genomic Precis Med 11, e002320.
26. Visser BJ, Meerveld-Gerrits J, Kroon D, et al. (2015). Assessing the quality of anti-malarial drugs from Gabonese pharmacies using the MiniLab: A field study. Malar J 14, 1–13.
27. Wang H, Zhang X, Xu X, et al. (2017). A portable microfluidic platform for rapid molecular diagnostic testing of patients with myeloproliferative neoplasms. Sci Rep 7, 1–11.
28. Wilke RA, Ramsey LB, Johnson SG, et al. (2012). The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin Pharmacol Ther 92, 112–117.
29. Zaky WI, Tomaino FR, Pilotte N, et al. (2018). Backpack PCR: A point-of-collection diagnostic platform for the rapid detection of Brugia parasites in mosquitoes. PLoS Negl Trop Dis 12, e0006962.
Acknowledgements
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