Abstract
The challenge of personalised medicine have been the centre of constructive debate in the last years, and have activated multidisciplinary approaches to solve the issues for translation to the clinic. In the preface, the editors summarise the challenges to translate genetic-based knowledge to the clinical setting. In this chapter, we will be reviewing the pre-requisites that will lessen the struggles associated with the implementation of pharmacogenetic testing protocols. To achieve this we will focus on the needs and recommendations to promote patient molecular classification to enhance risk assessment and drug response research; stratification of well-defined therapeutic groups, using genetic analysis, into subgroups of responders to specific therapies; the development of technologies and integrative information systems to provide the healthcare system with optimised and sustainable genetic testing protocols; the need of harmonised guidelines for the proper selection of patient groups for clinical trials; and advances in research to generate evidence based knowledge that can be smoothly translated for healthcare use.
Translation from research to the clinic is mainly associated with (1) the co-evolution of biomarkers and targeted therapy and (2) genotypes associated with drug metabolising enzymes. Although significant pharmacogenetic analyses are currently in use, the main obstacles associated with the efficient implementation include the uptake by the health care systems, incorporation into clinical guidelines as well as economic, educational, legal and commercial aspects. Understanding the approach for successful translation to clinical practice and resolving, in-part, the confounding aspects that negatively impact efficient implementation, shall support the transition from an empirical approach to a personalised health care system.
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Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. New Engl J Med 366(10):883–892. doi:10.1056/NEJMoa1113205
Druker BJ (2008) Translation of the Philadelphia chromosome into therapy for CML. Blood 112(13):4808–4817. doi:10.1182/blood-2008-07-077958
Stegmeier F, Warmuth M, Sellers WR, Dorsch M (2010) Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clin Pharmacol Ther 87(5):543–552. doi:10.1038/clpt.2009.297
Lum DW, Perel P, Hingorani AD, Holmes MV (2013) CYP2D6 genotype and tamoxifen response for breast cancer: a systematic review and meta-analysis. PLoS ONE 8(10):e76648. doi:10.1371/journal.pone.0076648
Ruddy KJ, Desantis SD, Gelman RS, Wu AH, Punglia RS, Mayer EL, Tolaney SM, Winer EP, Partridge AH, Burstein HJ (2013) Personalized medicine in breast cancer: tamoxifen, endoxifen, and CYP2D6 in clinical practice. Breast Cancer Res Treat 141(3):421–427. doi:10.1007/s10549-013-2700-1
Province MA, Goetz MP, Brauch H, Flockhart DA, Hebert JM, Whaley R, Suman VJ, Schroth W, Winter S, Zembutsu H, Mushiroda T, Newman WG, Lee MT, Ambrosone CB, Beckmann MW, Choi JY, Dieudonne AS, Fasching PA, Ferraldeschi R, Gong L, Haschke-Becher E, Howell A, Jordan LB, Hamann U, Kiyotani K, Krippl P, Lambrechts D, Latif A, Langsenlehner U, Lorizio W, Neven P, Nguyen AT, Park BW, Purdie CA, Quinlan P, Renner W, Schmidt M, Schwab M, Shin JG, Stingl JC, Wegman P, Wingren S, Wu AH, Ziv E, Zirpoli G, Thompson AM, Jordan VC, Nakamura Y, Altman RB, Ames MM, Weinshilboum RM, Eichelbaum M, Ingle JN, Klein TE (2014) CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clin Pharmacol Ther 95(2):216–227. doi:10.1038/clpt.2013.186
Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M (2013) A randomized trial of genotype-guided dosing of warfarin. New Engl J Med 369(24):2294–2303. doi:10.1056/NEJMoa1311386
Rosmarin D, Palles C, Church D, Domingo E, Jones A, Johnstone E, Wang H, Love S, Julier P, Scudder C, Nicholson G, Gonzalez-Neira A, Martin M, Sargent D, Green E, McLeod H, Zanger UM, Schwab M, Braun M, Seymour M, Thompson L, Lacas B, Boige V, Ribelles N, Afzal S, Enghusen H, Jensen SA, Etienne-Grimaldi MC, Milano G, Wadelius M, Glimelius B, Garmo H, Gusella M, Lecomte T, Laurent-Puig P, Martinez-Balibrea E, Sharma R, Garcia-Foncillas J, Kleibl Z, Morel A, Pignon JP, Midgley R, Kerr D, Tomlinson I (2014) Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: investigation in the QUASAR2 study, systematic review, and meta-analysis. J Clin Oncol 32(10):1031–1039. doi:10.1200/JCO.2013.51.1857
Colomer R, Monzo M, Tusquets I, Rifa J, Baena JM, Barnadas A, Calvo L, Carabantes F, Crespo C, Munoz M, Llombart A, Plazaola A, Artells R, Gilabert M, Lloveras B, Alba E (2008) A single-nucleotide polymorphism in the aromatase gene is associated with the efficacy of the aromatase inhibitor letrozole in advanced breast carcinoma. Clin Cancer Res 14(3):811–816. doi:10.1158/1078-0432.CCR-07-1923
Makeeva O, Stepanov V, Puzyrev V, Goldstein DB, Grossman I (2008) Global pharmacogenetics: genetic substructure of Eurasian populations and its effect on variants of drug-metabolizing enzymes. Pharmacogenomics 9(7):847–868. doi:10.2217/14622416.9.7.847
Haibe-Kains B, El-Hachem N, Birkbak NJ, Jin AC, Beck AH, Aerts HJ, Quackenbush J (2013) Inconsistency in large pharmacogenomic studies. Nature 504(7480):389–393. doi:10.1038/nature12831
Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER, 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA, 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH (2013) A pharmacogenetic versus a clinical algorithm for warfarin dosing. New Engl J Med 369(24):2283–2293. doi:10.1056/NEJMoa1310669
Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, Milligan PE, Grice G, Lenzini P, Rettie AE, Aquilante CL, Grosso L, Marsh S, Langaee T, Farnett LE, Voora D, Veenstra DL, Glynn RJ, Barrett A, McLeod HL (2008) Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 84(3):326–331. doi:10.1038/clpt.2008.10
Ross S, Anand SS, Joseph P, Pare G (2012) Promises and challenges of pharmacogenetics: an overview of study design, methodological and statistical issues. JRSM Cardiovasc Dis 1(1):2
Holmes MV, Shah T, Vickery C, Smeeth L, Hingorani AD, Casas JP (2009) Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies. PLoS ONE 4(12):e7960. doi:10.1371/journal.pone.0007960
Rae JM (2013) CYP2D6 genotype should not be used to determine endocrine therapy in postmenopausal breast cancer patients. Clin Pharmacol Ther 94(2):183–185. doi:10.1038/clpt.2013.102
Ratain MJ, Nakamura Y, Cox NJ (2013) CYP2D6 genotype and tamoxifen activity: understanding interstudy variability in methodological quality. Clin Pharmacol Ther 94(2):185–187. doi:10.1038/clpt.2013.66
Kaye C, Korf B (2013) Genetic Literacy and Competency. Pediatrics 132(Suppl):S224–S230. doi:10.1542/peds.2013-1032G
Skirton H, Lewis C, Kent A, Coviello DA (2010) Genetic education and the challenge of genomic medicine: development of core competences to support preparation of health professionals in Europe. Eur J Hum Genet 18(9):972–977. doi:10.1038/ejhg.2010.64
Englander R, Cameron T, Ballard AJ, Dodge J, Bull J, Aschenbrener CA (2013) Toward a common taxonomy of competency domains for the health professions and competencies for physicians. Acad Med 88(8):1088–1094. doi:10.1097/ACM.0b013e31829a3b2b
Korf BR (2013) Genomic medicine: educational challenges. Mol Genet Genomic Med 1(3):119–122. doi:10.1002/mgg3.38
Gurwitz D, Lunshof JE, Dedoussis G, Flordellis CS, Fuhr U, Kirchheiner J, Licinio J, Llerena A, Manolopoulos VG, Sheffield LJ, Siest G, Torricelli F, Vasiliou V, Wong S (2005) Pharmacogenomics education: international society of pharmacogenomics recommendations for medical, pharmaceutical, and health schools deans of education. Pharmacogenomics J 5(4):221–225. doi:10.1038/sj.tpj.6500312
Eeles R, Purland G, Maher J, Evans DG (2007) Delivering cancer genetics services–new ways of working. Fam Cancer 6(2):163–167. doi:10.1007/s10689-007-9137-9
Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE (2012) Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 92(4):414–417. doi:10.1038/clpt.2012.96
Relling M, Klein T (2011) CPIC: clinical pharmacogenetics implementation consortium of the pharmacogenomics research network. Clin Pharmacol Ther 89(3):464–467
Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286(5439):487–491
Burmester JK, Sedova M, Shapero MH, Mansfield E (2010) DMET microarray technology for pharmacogenomics-based personalized medicine. Methods Mol Biol 632:99–124. doi:10.1007/978-1-60761-663-47
Absalan F, Ronaghi M (2007) Molecular inversion probe assay. Methods Mol Biol 396:315–330
Johnson JA, Burkley BM, Langaee TY, Clare-Salzler MJ, Klein TE, Altman RB (2012) Implementing personalized medicine: development of a cost-effective customized pharmacogenetics genotyping array. Clin Pharmacol Ther 92(4):437–439. doi:10.1038/clpt.2012.125
Altman RB, Whirl-Carrillo M, Klein TE (2013) Challenges in the pharmacogenomic annotation of whole genomes. Clin Pharmacol Ther 94(2):211–213. doi:10.1038/clpt.2013.111
Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J (2011) Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 12(11):745–755. doi:10.1038/nrg3031
Gamazon ER, Perera M (2012) Genome-wide approaches in pharmacogenomics: heritability estimation and pharmacoethnicity as primary challenges. Pharmacogenomics 13(10):1101–1104. doi:10.2217/pgs.12.88
Metzker ML (2010) Sequencing technologies—the next generation. Nat Rev Genet 11(1):31–46. doi:10.1038/nrg2626
Fedurco M, Romieu A, Williams S, Lawrence I, Turcatti G (2006) BTA, a novel reagent for DNA attachment on glass and efficient generation of solid-phase amplified DNA colonies. Nucleic Acids Res 34(3):e22
Dressman D, Yan H, Traverso G, Kinzler KW, Vogelstein B (2003) Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. Proc Natl Acad Sci USA 100(15):8817–8822. doi:10.1073/pnas.1133470100
Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, Wang MD, Zhang K, Mitra RD, Church GM (2005) Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309(5741):1728–1732
Kim JB, Porreca GJ, Song L, Greenway SC, Gorham JM, Church GM, Seidman CE, Seidman JG (2007) Polony multiplex analysis of gene expression (PMAGE) in mouse hypertrophic cardiomyopathy. Science 316(5830):1481–1484
Leamon JH, Lee WL, Tartaro KR, Lanza JR, Sarkis GJ, deWinter AD, Berka J, Weiner M, Rothberg JM, Lohman KL (2003) A massively parallel PicoTiterPlate based platform for discrete picoliter-scale polymerase chain reactions. Electrophoresis 24(21):3769–3777. doi:10.1002/elps.200305646
Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Braslavsky I, Causey M, Colonell J, Dimeo J, Efcavitch JW, Giladi E, Gill J, Healy J, Jarosz M, Lapen D, Moulton K, Quake SR, Steinmann K, Thayer E, Tyurina A, Ward R, Weiss H, Xie Z (2008) Single-molecule DNA sequencing of a viral genome. Science 320(5872):106–109. doi:10.1126/science.1150427
Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, Peluso P, Rank D, Baybayan P, Bettman B, Bibillo A, Bjornson K, Chaudhuri B, Christians F, Cicero R, Clark S, Dalal R, Dewinter A, Dixon J, Foquet M, Gaertner A, Hardenbol P, Heiner C, Hester K, Holden D, Kearns G, Kong X, Kuse R, Lacroix Y, Lin S, Lundquist P, Ma C, Marks P, Maxham M, Murphy D, Park I, Pham T, Phillips M, Roy J, Sebra R, Shen G, Sorenson J, Tomaney A, Travers K, Trulson M, Vieceli J, Wegener J, Wu D, Yang A, Zaccarin D, Zhao P, Zhong F, Korlach J, Turner S (2009) Real-time DNA sequencing from single polymerase molecules. Science 323(5910):133–138. doi:10.1126/science.1162986
Erlich Y, Mitra PP, delaBastide M, McCombie WR, Hannon GJ (2008) Alta-Cyclic: a self-optimizing base caller for next-generation sequencing. Nat Methods 5(8):679–682. doi:10.1038/nmeth.1230
Metzker ML (2009) Sequencing in real time. Nat Biotechnol 27(2):150–151. doi:10.1038/nbt0209-150
Mardis ER (2008) Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet 9:387–402. doi:10.1146/annurev.genom.9.081307.164359
Landegren U, Kaiser R, Sanders J, Hood L (1988) A ligase-mediated gene detection technique. Science 241(4869):1077–1080
Ronaghi M, Karamohamed S, Pettersson B, Uhlen M, Nyren P (1996) Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem 242 (1):84–89
Ronaghi M, Uhlen M, Nyren P (1998) A sequencing method based on real-time pyrophosphate. Science 281(5375):363, 365
Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, Carnevali P, Nazarenko I, Nilsen GB, Yeung G, Dahl F, Fernandez A, Staker B, Pant KP, Baccash J, Borcherding AP, Brownley A, Cedeno R, Chen L, Chernikoff D, Cheung A, Chirita R, Curson B, Ebert JC, Hacker CR, Hartlage R, Hauser B, Huang S, Jiang Y, Karpinchyk V, Koenig M, Kong C, Landers T, Le C, Liu J, McBride CE, Morenzoni M, Morey RE, Mutch K, Perazich H, Perry K, Peters BA, Peterson J, Pethiyagoda CL, Pothuraju K, Richter C, Rosenbaum AM, Roy S, Shafto J, Sharanhovich U, Shannon KW, Sheppy CG, Sun M, Thakuria JV, Tran A, Vu D, Zaranek AW, Wu X, Drmanac S, Oliphant AR, Banyai WC, Martin B, Ballinger DG, Church GM, Reid CA (2010) Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327(5961):78–81. doi:10.1126/science.1181498
Shendure J, Ji H (2008) Next-generation DNA sequencing. Nat Biotechnol 26(10):1135–1145. doi:10.1038/nbt1486
Chaisson MJ, Brinza D, Pevzner PA (2009) De novo fragment assembly with short mate-paired reads: Does the read length matter? Genome Res 19(2):336–346. doi:10.1101/gr.079053.108
Trapnell C, Salzberg SL (2009) How to map billions of short reads onto genomes. Nat Biotechnol 27(5):455–457. doi:10.1038/nbt0509-455n
Flicek P, Birney E (2009) Sense from sequence reads: methods for alignment and assembly. Nat Methods 6(11 Suppl):S6–S12. doi:10.1038/nmeth.1376
Simpson JT, Wong K, Jackman SD, Schein JE, Jones SJ, Birol I (2009) ABySS: a parallel assembler for short read sequence data. Genome Res 19(6):1117–1123. doi:10.1101/gr.089532.108
Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753. doi:10.1038/nature08494i]
Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, Belmont JW, Boudreau A, Hardenbol P, Leal SM, Pasternak S, Wheeler DA, Willis TD, Yu F, Yang H, Zeng C, Gao Y, Hu H, Hu W, Li C, Lin W, Liu S, Pan H, Tang X, Wang J, Wang W, Yu J, Zhang B, Zhang Q, Zhao H, Zhou J, Gabriel SB, Barry R, Blumenstiel B, Camargo A, Defelice M, Faggart M, Goyette M, Gupta S, Moore J, Nguyen H, Onofrio RC, Parkin M, Roy J, Stahl E, Winchester E, Ziaugra L, Altshuler D, Shen Y, Yao Z, Huang W, Chu X, He Y, Jin L, Liu Y, Sun W, Wang H, Wang Y, Xiong X, Xu L, Waye MM, Tsui SK, Xue H, Wong JT, Galver LM, Fan JB, Gunderson K, Murray SS, Oliphant AR, Chee MS, Montpetit A, Chagnon F, Ferretti V, Leboeuf M, Olivier JF, Phillips MS, Roumy S, Sallee C, Verner A, Hudson TJ, Kwok PY, Cai D, Koboldt DC, Miller RD, Pawlikowska L, Taillon-Miller P, Xiao M, Tsui LC, Mak W, Song YQ, Tam PK, Nakamura Y, Kawaguchi T, Kitamoto T, Morizono T, Nagashima A, Ohnishi Y, Sekine A, Tanaka T, Tsunoda T, Deloukas P, Bird CP, Delgado M, Dermitzakis ET, Gwilliam R, Hunt S, Morrison J, Powell D, Stranger BE, Whittaker P, Bentley DR, Daly MJ, de Bakker PI, Barrett J, Chretien YR, Maller J, McCarroll S, Patterson N, Pe'er I, Price A, Purcell S, Richter DJ, Sabeti P, Saxena R, Schaffner SF, Sham PC, Varilly P, Stein LD, Krishnan L, Smith AV, Tello-Ruiz MK, Thorisson GA, Chakravarti A, Chen PE, Cutler DJ, Kashuk CS, Lin S, Abecasis GR, Guan W, Li Y, Munro HM, Qin ZS, Thomas DJ, McVean G, Auton A, Bottolo L, Cardin N, Eyheramendy S, Freeman C, Marchini J, Myers S, Spencer C, Stephens M, Donnelly P, Cardon LR, Clarke G, Evans DM, Morris AP, Weir BS, Mullikin JC, Sherry ST, Feolo M, Skol A, Zhang H, Matsuda I, Fukushima Y, Macer DR, Suda E, Rotimi CN, Adebamowo CA, Ajayi I, Aniagwu T, Marshall PA, Nkwodimmah C, Royal CD, Leppert MF, Dixon M, Peiffer A, Qiu R, Kent A, Kato K, Niikawa N, Adewole IF, Knoppers BM, Foster MW, Clayton EW, Watkin J, Muzny D, Nazareth L, Sodergren E, Weinstock GM, Yakub I, Birren BW, Wilson RK, Fulton LL, Rogers J, Burton J, Carter NP, Clee CM, Griffiths M, Jones MC, McLay K, Plumb RW, Ross MT, Sims SK, Willey DL, Chen Z, Han H, Kang L, Godbout M, Wallenburg JC, L'Archeveque P, Bellemare G, Saeki K, An D, Fu H, Li Q, Wang Z, Wang R, Holden AL, Brooks LD, McEwen JE, Guyer MS, Wang VO, Peterson JL, Shi M, Spiegel J, Sung LM, Zacharia LF, Collins FS, Kennedy K, Jamieson R, Stewart J (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449(7164):851–861
LaFramboise T (2009) Single nucleotide polymorphism arrays: a decade of biological, computational and technological advances. Nucleic Acids Res 37(13):4181–4193. doi:10.1093/nar/gkp552
Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA (2010) Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. New Engl J Med 362(13):1181–1191. doi:10.1056/NEJMoa0908094
Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M, Shendure J, Drmanac R, Jorde LB, Hood L, Galas DJ (2010) Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328(5978):636–639. doi:10.1126/science.1186802
Anderson MW, Schrijver I (2010) Next generation DNA sequencing and the future of genomic medicine. Genes (Basel) 1(1):38–69. doi:10.3390/genes1010038
Peters BA, Kermani BG, Sparks AB, Alferov O, Hong P, Alexeev A, Jiang Y, Dahl F, Tang YT, Haas J, Robasky K, Zaranek AW, Lee JH, Ball MP, Peterson JE, Perazich H, Yeung G, Liu J, Chen L, Kennemer MI, Pothuraju K, Konvicka K, Tsoupko-Sitnikov M, Pant KP, Ebert JC, Nilsen GB, Baccash J, Halpern AL, Church GM, Drmanac R (2012) Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells. Nature 487(7406):190–195. doi:10.1038/nature11236
Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42 (D1):D980–D985. doi:10.1093/nar/gkt1113
Zheng CJ, Han LY, Xie B, Liew CY, Ong S, Cui J, Zhang HL, Tang ZQ, Gan SH, Jiang L, Chen YZ (2007) PharmGED: pharmacogenetic effect database. Nucleic Acids Res 35(Database):D794–D799. doi:10.1093/nar/gkl853
Kho AN, Rasmussen LV, Connolly JJ, Peissig PL, Starren J, Hakonarson H, Hayes MG (2013) Practical challenges in integrating genomic data into the electronic health record. Genet Med 15(10):772–778. doi:10.1038/gim.2013.131
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Grech, G., van Schaik, R., Borg, J. (2015). Implementation of Genomic Medicine: Tools and Challenges. In: Grech, G., Grossman, I. (eds) Preventive and Predictive Genetics: Towards Personalised Medicine. Advances in Predictive, Preventive and Personalised Medicine, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-15344-5_12
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