Personalized Medicine: The Future of Health Care

Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya

doi:10.18585/inabj.v8i3.271

Personalized Medicine: The Future of Health Care

Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

Abstract

BACKGROUND: Most medical treatments have been designed for the “average patients”. As a result of this “one-size-fits-all-approach”, treatments can be very successful for some patients but not for others. The issue is shifting by the new innovation approach in diseases treatment and prevention, precision medicine, which takes into account individual differences in people’s genes, environments, and lifestyles. This review was aimed to describe a new approach of healthcare performance strategy based on individual genetic variants.

CONTENT: Researchers have discovered hundreds of genes that harbor variations contributing to human illness, identified genetic variability in patients’ responses to different of treatments, and from there begun to target the genes as molecular causes of diseases. In addition, scientists are developing and using diagnostic tests based on genetics or other molecular mechanisms to better predict patients’ responses to targeted therapy.

SUMMARY: Personalized medicine seeks to use advances in knowledge about genetic factors and biological mechanisms of disease coupled with unique considerations of an individual’s patient care needs to make health care more safe and effective. As a result of these contributions to improvement in the quality of care, personalized medicine represents a key strategy of healthcare reform.

KEYWORDS: precision medicine, genomic, proteomic, metabolomic

Full Text:

PDF

References

Ginsburg GS, Willard HF. Genomic and personalized medicine: foundations and applications. Transl Res. 2009; 154: 277-87, CrossRef.

Topol EJ. Individualized medicine from prewomb to tomb. Cell. 2014; 157: 241-53, CrossRef.

FDA. Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development. Maryland: U.S. Food and Drug Administration: 2013, article.

Blaus A, Madabushi R, Pacanoski M, Rose M, Schuck RN, Stockbridge N, et al. Personalized cardiovascular medicine today: a Food and Administration/Center for Drug evaluation and research perspective. Circulation. 2015; 132: 1425-32, CrossRef.

The White House [Internet]. Fact Sheet: President Obama’s Precision Medicine Initiative [update 2015 Jan 30, cited 2016 Jul 29]. Available from: https://www.whitehouse.gov/.

National Research Council. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington DC: The National Academies Press; 2011, CrossRef.

Aronson SJ, Rehm HL. Building the foundation for genomics in precision medicine. Nature. 2015; 526: 336-42, CrossRef.

Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, et al. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther. 2013; 93: 324-5, CrossRef.

Korf BR, Rehm HL. New approaches to molecular diagnosis. J Am Med Assoc. 2013; 309: 1511-21, CrossRef.

Hoffman MA, Williams MS. Electronic medical records and personalized medicine. Hum Genet. 2011; 130: 33-9, CrossRef.

Del Fiol G. Williams MS, Maram N, Rocha RA, Wood GM, Mitchell JA. Integrating genetic information resources with an EHR. AMIA Annu Symp Proc. 2006; 2006: 904, PMID.

Béroud C, Collod-Béroud G, Boileau C, Soussi T, Junien C. UMD (Universal mutation database): a generic software to build and analyze locus-specific databases. Hum Mutat. 2000; 15: 86-94, CrossRef.

Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nature Genet. 2013; 45: 1160-7, CrossRef.

Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D, et al. DECIPHER: Database of chromosomal imbalance and phenotype in humans using ensembl resources. Am J Hum Genet. 2009; 84: 524-33, CrossRef.

Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first- tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010; 86: 749-64, CrossRef.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, et al. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nature Genet. 2014; 46: 107-15, CrossRef.

Tryka KA, Hao L, Sturcke A, Jin Y, Wang ZY, Ziyabari L, et al. NCBI’s Database of Genotypes and Phenotypes: dbGaP. Nucleic Acids Res. 2014; 42: D975-9, CrossRef.

Zhang J, Baran J, Cros A, Guberman JM, Haider S, Hsu J, et al. International Cancer Genome Consortium Data Portal -- a one-stop shop for cancer genomics data. Database (Oxford). 2011; 2011: bar026, CrossRef.

The Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nature Genet. 2013; 45: 1113-20, CrossRef.

Schilsky RL, Michels DL, Kearbey AH, Yu PP, Hudis CA. Building a rapid learning health care system for oncology: the regulatory framework of CancerLinQ. J Clin Oncol. 2014; 32: 2373-9, CrossRef.

Nicholson JK. Global systems biology, personalized medicine and molecular epidemiology. Mol Sys Biol. 2006; 2: 52, CrossRef.

MacArthur DG, Balasubramanian S, Frankish A, Huang N, Morris J, Walter K, et al. A Systematic survey of loss-of-function variants in human protein-coding genes. Science. 2012; 335: 823-8, CrossRef.

Ahrens CH, Brunner E, Qeli E, Basler K, Aebersold R. Generating and navigating proteome maps using mass spectrometry. Nature Rev Mol Cell Biol. 2010; 11: 789-801, CrossRef.

Bensimon A, Heck AJ, Aebersold R. Mass spectrometry-based proteomics and network biology. Annu Rev Biochem. 2012; 81: 379-405, CrossRef.

Richards AL, Merrill AE, Coon JJ. Proteome sequencing goes deep. Curr Opin Chem Biol. 2015; 24: 11-7, CrossRef.

Walther TC, Mann M. Mass spectrometry-based proteomics in cell biology. J Cell Biol. 2010; 190: 491-500, CrossRef.

Larance M, Lamond AI. Multidimensional proteomics for cell biology. Nat Rev Mol Cell Biol. 2015; 16: 269-80, CrossRef.

Nicholson JK, Connelly J, Lindon JC, Holmes E. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 2002; 1: 153-61, CrossRef.

Clish CB. Metabolomics: an emerging but powerful tool for precision medicine. Cold Spring Harb Mol Case Stud. 2015; 1: a000588, CrossRef.

Kuehnbaum NL, Britz-McKibbin P. New advances in separation science for metabolomics: resolving chemical diversity in a post-genomic era. Chem Rev. 2013; 113: 2437-68, CrossRef.

Gieger C, Geistlinger L, Altmaier E, de Angelis MH, Kronenberg F, Meitinger T, et al. Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum. Plos Gen. 2008; 4: e1000282, CrossRef.

Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, et al. HMDB 3.0 -- the human metabolome database in 2013. Nucleic Acids Res. 2013; 41: D801-7, CrossRef.

Mayers JR, Wu C, Clish CB, Kraft P, Torrence ME, Fiske BP, et al. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med. 2014; 20: 1193-8, CrossRef.

Rhee EP, Cheng S, Larson MG, Walford GA, Lewis GD, McCabe E, et al. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Invest. 2011; 121: 1402-11, CrossRef.

Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011; 17: 448-53, CrossRef.

Wang TJ, Ngo D, Psychogios N, Dejam A, Larson MG, Vasan RS, et al. 2-aminoadipic acid is a biomarker for diabetes risk. J Clin Invest. 2013; 123: 4309-17, CrossRef.

Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, MacArthur LH, et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014; 20: 415-8, CrossRef.

Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009; 9: 311-26, CrossRef.

Baynam G, Walters M, Claes P, Kung S, LeSouef P, Dawkins H, et al. Phenotyping: targeting genotype’s rich cousin for diagnosis. J Paediatr Child Health. 2015; 51: 381-6, CrossRef.

Fernald GH, Capriotti E, Daneshjou R, Karczewski KJ, Altman RB. Bioinformatics challenges for personalized medicine. Bioinformatics. 2011; 27: 1741-8, http://dx.doi.org/10.1093/bioinformatics/btr295">CrossRef.

Robinson PN, Mungall CJ, Haendel M. Capturing phenotypes for precision medicine. Cold Spring Harb Mol Case Stud. 2015; 1: a000372, CrossRef.

Robinson PN. Deep phenotyping for precision medicine. Hum Mutat. 2012; 33: 777-80, CrossRef.

Riggs ER, Jackson L, Miller DT, Van Vooren S. Phenotypic information in genomic variant databases enhances clinical care and research: the International Standards for Cytogenomic Arrays Consortium experience. Hum Mutat. 2012; 33: 787-96, CrossRef.

Thakuria JV, Zaranek AW, Church GM, Berry GT. Back to the future: from genome to metabolome. Hum Mutat. 2012; 33: 809-12, CrossRef.

Taboada M, Rodríguez H, Martínez D, Pardo M, Sobrido MJ. Automated semantic annotation of rare disease cases: a case study. Database (Oxford). 2014; 2014 pii: bau045, CrossRef.

Kuleshov V, Xie D, Chen R, Pushkarev D, Ma Z, Blauwkamp T, et al. Whole-genome haplotyping using long reads and statistical methods. Nat Biotechnol. 2014; 32: 261-6, CrossRef.

Welch KO, Marin RS, Pandya A, Arnos KS. Compound heterozygosity for dominant and recessive GJB2 mutations: effect on phenotype and review of the literature. Am J Med Genet A. 2007; 143A: 1567-73, CrossRef.

Fong CYI, Mumford AD, Likeman MJ, Jardine PE. Cerebral palsy in siblings caused by compound heterozygous mutations in the gene encoding protein C. Dev Med Child Neurol. 2010; 52: 489-93, CrossRef.

Shimizu H, Takizawa Y, Pulkkinen L, Murata S, Kawai M, Hachisuka H, et al. Epidermolysis bullosa simplex associated with muscular dystrophy: phenotype-genotype correlations and review of the literature. J Am Acad Dermatol. 1999; 41: 950-6, CrossRef.

Tewhey R, Bansal V, Torkamani A, Topol EJ, Schork NJ. The importance of phase information for human genomics. Nat Rev Genet. 2011; 12: 215-23, CrossRef.

Browning SR, Browning BL. Haplotype phasing: existing methods and new developments. Nat Rev Genet. 2011; 12: 703-14, CrossRef.

Kitzman JO, Mackenzie AP, Adey A, Hiatt JB, Patwardhan RP, Sudmant PH, et al. Haplotype-resolved genome sequencing of a Gujarati Indian individual. Nat Biotechnol. 2011; 29: 59-63, CrossRef.

Fan HC, Wang J, Potanina A, Quake SR. Whole-genome molecular haplotyping of single cells. Nat Biotechnol. 2011; 29: 51-7, CrossRef.

Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, et al. A draft sequence of the Neandertal genome. Science. 2010; 328: 710-22, CrossRef.

Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001; 409: 860-921, CrossRef.

Li R, Li Y, Fang X, Yang H, Wang J, Kristiansen K,et al. SNP detection for massively parallel whole-genome resequencing. Genome Res. 2009; 19: 1124-32, CrossRef.

Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25: 1754-60, CrossRef.

DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011; 43: 491-8, CrossRef.

Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, et al. The diploid genome sequence of an individual human. PLoS Biol. 2007; 5: e254, CrossRef.

Wang J, Wang W, Li R, Li Y, Tian G, Goodman L, et al. The diploid genome sequence of an Asian individual. Nature. 2008; 456: 60-5, CrossRef.

Ahn SM, Kim TH, Lee S, Kim D, Ghang H, Kim DS, et al. The first Korean genome sequence and analysis: full genome sequencing for a socio-ethnic group. Genome Res. 2009; 19: 1622-9, CrossRef.

Tong P, Prendergast JG, Lohan AJ, Farrington SM, Cronin S, Friel N, et al. Sequencing and analysis of an Irish human genome. Genome Biol. 2010; 11: R91, CrossRef.

Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, et al. A map of human genome variation from population-scale sequencing. Nature. 2010; 467: 1061-73, CrossRef.

International HapMap Consortium. A haplotype map of the human genome. Nature. 2005; 437: 1299-320, CrossRef.

Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491: 56-65, CrossRef.

Cao H, Wu H, Luo R, Huang S, Sun Y, Tong X, et al. De Novo assembly of a haplotype-resolved human genome. Nat Biotechnol. 2015; 33: 617-22, CrossRef.

Browning SR, Browning BL. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am J Hum Genet. 2007; 81: 1084-97, CrossRef.

Duitama J, McEwen GK, Huebsch T, Palczewski S, Schulz S, Verstrepen K, et al. Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of single individual haplotyping techniques. Nucleic Acids Res. 2012; 40: 2041-53, CrossRef.

Woolley AT, Guillemette C, Li Cheung C, Housman DE, Lieber CM. Direct haplotyping of kilobase-size DNA using carbon nanotube probes. Nat Biotechnol. 2000; 18: 760-3, CrossRef.

Cao H, Wang Y, Zhang W, Chai X, Zhang X, Chen S, et al. A short-read multiplex sequencing method for reliable, cost-effective and high-throughput genotyping in large-scale studies. Hum Mutat. 2013; 34: 1715-20, CrossRef.

Dapprich J, Ferriola D, Magira EE, Kunkel M, Monos D. SNP-specific extraction of haplotype-resolved targeted genomic regions. Nucleic Acids Res. 2008; 36: e94, CrossRef.

Suk EK, McEwen GK, Duitama J, Nowick K, Schulz S, Palczewski S, et al. A comprehensively molecular haplotype-resolved genome of a European individual. Genome Res. 2011; 21: 1672-85, CrossRef.

ABPI. The stratification of disease for personalised medicines: Research driven recommendations to strengthen a unified UK strategy through a stakeholder alliance. London: The Association of the British Pharmaceutical Industry; 2014, article.

[N.A.]. The coming era of human phenotyping. Nat Biotechnol. 2015; 6: 567, CrossRef.

Relling MV, Evans WE. Pharmacogenomic in the clinic. Nature. 2015; 526: 343-50, CrossRef.

Kinch MS, Haynesworth A, Kinch SL, Hoyer D. An overview of FDA-approved new molecular entities: 1827-2013. Drug Discov Today. 2014; 19: 1033-9, CrossRef.

Ehmann F, Caneva L, Prasad K, Paulmichl M, Maliepaard M, Llerena A, et al. Pharmacogenomic information in drug labels: European Medicines Agency perspective. Pharmacogenomics J. 2015; 15: 201-10, CrossRef.

Ishiguro A, Yagi S, Uyama Y. Characteristics of pharmacogenomics/ biomarker-guided clinical trials for regulatory approval of anti-cancer drugs in Japan. J Hum Genet. 2013; 58: 313-6, CrossRef.

U.S. Food and Drug Administration [Internet]. Table of Pharmacogenomic Biomarkers in Drug Labeling [updated 2016 Jul 11, cited 2016 Jul 29]. Available from: CrossRef.

CPIC (Clinical Pharmacogenetics Implementation Consortium) [Internet]. Genes – Drugs [updated 2016 May 13; cited 2016 Jul 29]. Available from: https://cpicpgx.org/.

Dunnenberger HM, Crews KR, Hoffman JM, Caudle KE, Broeckel U, Howard SC, et al. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annu Rev Pharmacol Toxicol. 2015; 55: 89-106, CrossRef.

Buchanan J, Wordsworth S, Schuh A. Issues surrounding the health economic evaluation of genomic technologies. Pharmacogenomics. 2013; 14: 1833-47, CrossRef.

Schroeder SA, Frist W. Phasing out fee-for-service payment. N Engl J Med. 2013; 368: 2029-32, CrossRef.

Levy KD, Decker BS, Carpenter JS, Flockhart DA, Dexter PR, Desta Z, et al. Prerequisites to implementing a pharmacogenomics program in a large health-care system. Clin Pharmacol Ther. 2014; 96: 307-9, CrossRef.

Gordon AS, Tabor HK, Johnson AD, Snively BM, Assimes TL, Auer PL, et al. Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset. Hum Mol Genet. 2014; 23: 1957-63, CrossRef.

Chen Z, Liew D, Kwan P. Effects of a HLA-B*15:02 screening policy on antiepileptic drug use and severe skin reactions. Neurology. 2014; 83: 2077-84, CrossRef.

Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014; 42: D980-5, CrossRef.

Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP, Landrum MJ, et al. ClinGen -- the Clinical Genome Resource. N Engl J Med. 2015; 372: 2235-42, CrossRef.

Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012; 92: 414-7, CrossRef.

Carter RF. Adapting next generation technologies to clinical molecular oncology service. Clin Lab News. 2015; 2015: 22-8, article.

Dorschner MO, Amendola LM, Shirts BH, Kiedrowski L, Salama J, Gordon AS, et al. Refining the structure and content of clinical genomic reports. Am J Med Genet C Semin Med Genet. 2014; 1: 85-92, CrossRef.

Brazil M. Genomics technologies march into new markets. Med

Tech Deal Makers. P:M8. Available from: https://biopharmadealmakers.nature.com/.

Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA. 1977; 74: 5463-7, CrossRef.

Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science. 2001; 291: 1304-51, CrossRef.

Cahill TJ, Ashrafian H, Watkins H. Genetic cardiomyopathies causing heart failure. Circ Res. 2013; 113: 660-75, CrossRef.

Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003; 34: 154-6, CrossRef.

George AL Jr. Molecular and genetic basis of sudden cardiac death. J Clin Invest. 2013; 123: 75-83, CrossRef.

Marian AJ. Recent developments in cardiovascular genetics and genomics. Circ Res. 2014; 115: e11-7, CrossRef.

Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT. Pulmonary arterial hypertension: the clinical syndrome. Circ Res. 2014; 115: 115-30, CrossRef.

Marian AJ. Medical DNA sequencing. Curr Opin Cardiol. 2011; 26: 175-80, CrossRef.

Marian AJ, Belmont J. Strategic approaches to unraveling genetic causes of cardiovascular diseases. Circ Res. 2011; 108: 1252-69, CrossRef.

Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature. 2012; 488: 471-5, CrossRef.

Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, at al. A map of human genome variation from population-scale sequencing. Nature. 2010; 467: 1061-73, CrossRef.

Keinan A, Clark AG. Recent explosive human population growth has resulted in an excess of rare genetic variants. Science. 2012; 336: 740-3, CrossRef.

Marian AJ. The bottleneck in genetic testing. Circ Res. 2015; 117: 586-8, CrossRef.

Liu L, Li Y, Li S, Hu N, He Y, Pong R, et al. Comparison of next-generation sequencing systems. J Biomed Biotechnol. 2012; 2012: 251364, CrossRef.

Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci USA. 1977; 74: 560-4, CrossRef.

Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975; 94: 441-8, CrossRef.

Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008; 456: 53-9, CrossRef.

Mardis ER. The impact of next-generation sequencing technology on genetics. Trends Genet. 2008; 24: 133-41, CrossRef.

Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet. 2008; 9: 387-402, CrossRef.

Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature. 2005; 437: 376-80, CrossRef.

Metzker ML. Sequencing technologies: the next generation. Nat Rev Genet. 2010; 11: 31-46, CrossRef.

Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M, et al. An integrated semiconductor device enabling non-optical genome sequencing. Nature. 2011; 475: 348-52, CrossRef.

Schuster SC. Next-generation sequencing transforms today’s biology. Nat Methods. 2008; 5: 16-8, CrossRef.

Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008; 26: 1135-45, CrossRef.

Valouev A, Ichikawa J, Tonthat T, Stuart J, Ranade S, Peckham H, et al. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res. 2008; 18: 1051-63, CrossRef.

Hutchison CA 3rd. DNA sequencing: bench to bedside and beyond. Nucleic Acids Res. 2007; 35: 6227-37, CrossRef.

Metzker ML. Emerging technologies in DNA sequencing. Genome Res. 2005; 15: 1767-76, CrossRef.

Mardis ER. A decade’s perspective on DNA sequencing technology. Nature. 2011; 470: 198-203, CrossRef.

Aziz N, Zhao Q, Bry L, Driscoll D, Funke B, Gibson JS, et al. College of American Pathologists’ laboratory standards for next-generation sequencing clinical tests. Arch Pathol Lab Med. 2015; 139: 481-93, CrossRef.

Gargis AS, Kalman L, Berry MW, Bick DP, Dimmock DP, Hambuch T, et al. Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol 2012; 30: 1033-6, CrossRef.

Rehm HD, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, et al. ACMG clinical laboratory standards for next-generation sequencing. Gen Med. 2013; 15: 733-47, CrossRef.

Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA. 2009; 106: 9362-7, CrossRef.

Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science. 2010; 327: 78-81, CrossRef.

Ashley EA, Butte AJ, Wheeler MT, Chen R, Klein TE, Dewey FE, et al. Clinical assessment incorporating a personal genome. Lancet. 2010; 375: 1525-35, CrossRef.

Collins FS, Guyer MS, Charkravarti A. Variations on a theme: cataloging human DNA sequence variation. Science. 1997; 278, 1580-1, CrossRef.

Keutgen XM, Filicori F, Crowley MJ, Wang Y, Scognamiglio T, Hoda R, et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res. 2012; 18: 2032-8, CrossRef.

Sboner A, Elemento O. A primer on precision medicine informatics. Brief Bioinform. 2016; 17: 145-53, CrossRef.

Servant N, Romejon J, Gestraud P, La Rosa P, Lucotte G, Lair S, et al. Bioinformatics for precision medicine in oncology: principles and application to the SHIVA clinical trial. Front Genet. 2014; 5: 152, CrossRef.

Luscombe NM, Greenbaum D, Gerstein M. What is bioinformatics? An introduction and overview. Yearb Med Inform. 2001; 2001: 83-100, article.

Bernstein FC, Koetzle TF, Williams GJ, Meyer EF Jr, Brice MD, Rodgers JR, et al. The Protein Data Bank. A computer-based archival file for macromolecular structures. Eur J Biochem. 1977; 80: 319-24, CrossRef.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The Protein Data Bank. Nucleic Acids Res. 2000; 28: 235-42, CrossRef.

Pearson WR, Lipman DJ. Improved tools for biological sequence comparison. Proc Natl Acad Sci USA. 1988; 85: 2444-8, CrossRef.

Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997; 25: 3389-402, CrossRef.

Bender E. Big data in biomedicine. Nature. 2015; 527: S1, CrossRef.

Green ED, Guyer MS, National Human Genome Research I. Charting a course for genomic medicine from base pairs to bedside. Nature. 2011; 470: 204-13, CrossRef.

Manolio TA, Chisholm RL, Ozenberger B, Roden DM, Williams MS, Wilson R, et al. Implementing genomic medicine in the clinic: The future is here. Genet Med. 2013; 15: 258-67, CrossRef.

Lazaridis KN, McAllister TM, Babovic-Vuksanovic D, Beck SA, Borad MJ, Bryce AH, et al. Implementing individualized medicine into the medical practice.m J Med Gen C Semin Med Genet. 2014; 166C: 15-23, CrossRef.

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100: 57-70, CrossRef.

Chin L, Gray JW. Translating insights from the cancer genome into clinical practice. Nature. 2008; 452: 553-63, CrossRef.

Andre F, Mardis E, Salm M, Soria JC, Siu LL, Swanton C. Prioritizing targets for precision cancer medicine. Ann Oncol. 2014; 25: 2295-303, CrossRef.

Stratton MR. Exploring the genomes of cancer cells: progress and promise. Science. 2011; 331: 1553-8, CrossRef.

Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009; 458: 719-24, CrossRef.

Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, Bernabé RR, et al. International network of cancer genome projects. Nature. 2010; 464: 993-8, CrossRef. Erratum in: Nature. 2010; 465: 966, CrossRef.

The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008; 455: 1061-8, CrossRef. Erratum in: Nature. 2013; 494: 506, CrossRef.

Chin L, Andersen JN, Futreal PA. Cancer genomics: from discovery science to personalized medicine. Nature Med. 2011; 17: 297-303, CrossRef.

Zhang B, Wang J, Wang X, Zhu J, Liu Q, Shi Z, et al. Proteogenomic characterization of human colon and rectal cancer. Nature. 2014; 513: 382-7, CrossRef.

Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004; 364: 1127-34, CrossRef.

Gerber DE, Minna JD. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell. 2010; 18: 548-51, CrossRef.

Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012; 366: 707-14, CrossRef.

Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011; 365: 1273-83, CrossRef.

Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013; 368: 2385-94, CrossRef.

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mated EGFR. N Engl J Med. 2010; 362: 2380-8, CrossRef.

Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustiutn G, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014; 15: 852-61, CrossRef.

Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. J Am Med Assoc. 2014; 311: 1998-2006, CrossRef.

Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015; 372: 1689-99, CrossRef.

Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002; 347: 472-80, CrossRef.

Green ED, Guyer MS, National Human Genome Research Institute. Charting a course for genomic medicine from base pairs to bedside. Nature. 2011; 470: 204-13, CrossRef.

Blankin AV, Piantadosi S, Hollingsworth SI. Patient-centric trials for therapeutic development in precision oncology. Nature. 2015; 526: 361-70, CrossRef.

Griffin JL, Shockcor JP. Metabolic profiles of cancer cells. Nat Rev Cancer. 2004; 4: 551-61, CrossRef.

Mendes P, Kell DB, Westerhoff HV. Why and when channeling can decrease pool size at constant net flux in a simple dynamic channel. Biochim Biophys Acta. 1996; 1289: 175-86, CrossRef.

Mendes P, Kell DB, Westerhoff HV. Channelling can decrease pool size. Eur J Biochem. 1992; 204: 257-66, CrossRef.

Boros LG, Lerner MR, Morgan DL, Taylor SL, Smith BJ, Postier RG, et al. [1,2-13C2]-D-glucose profiles of the serum, liver, pancreas, and DMBA-induced pancreatic tumors of rats. Pancreas. 2005; 31: 337-43, CrossRef.

Spratlin JL, Serkova NJ, Eckhardt SG. Clinical applications of metabolomics in oncology: a review. Clin Cancer Res. 2009; 15: 431-40, CrossRef.

Meric-Bernstam F, Farhangfar C, Mendelsohn J, Mills B. Building a personalized medicine infrastructure at a major cancer center. J Clin Oncol. 2013; 31: 1849-57, CrossRef.

Cerrone M, Napolitano C, Priori SG. Genetics of ion-channel disorders. Curr Opin Cardiol. 2012; 27: 242-52, CrossRef.

Moore JR, Leinwand L, Warshaw DM. Understanding cardiomyopathy phenotypes based on the functional impact of mutations in the myosin motor. Circ Res. 2012; 111: 375-85, CrossRef.

Fouchier SW, Dallinga-Thie GM, Meijers JC, Zelcer N, Kastelein JJ, Defesche JC, et al. Mutations in STAP1 are associated with autosomal dominant hypercholesterolemia. Circ Res. 2014; 115: 552-5, CrossRef.

Simino J, Kume R, Kraja AT, Turner ST, Hanis CL, Sheu WH, et al. Linkage analysis incorporating gene-age interactions identifies seven novel lipid loci: the Family Blood Pressure Program. Atherosclerosis. 2014; 235: 84-93, CrossRef.

Rosenthal EA, Ranchalis J, Crosslin DR, Burt A, Brunzell JD, Motulsky AG, et al. Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia. Am J Hum Genet. 2013; 93: 1035-45, CrossRef.

Malandrino N, Smith RJ. Peronalized medicine in diabetes. Clin Chem. 2011; 57: 231-40, CrossRef.

Smith RJ, Nathan DM, Arslanian SA, Groop L, Rizza RA, Rotter JI. Individualizing therapies in type 2 diabetes mellitus based on patient characteristics: what we know and what we need to know. J Clin Endocrinol Metab. 2010; 95: 1566-74, CrossRef.

Muller G. Personalized prognosis and diagnosis of type 2 diabetes: vision or fiction? Pharmacology. 2010; 85: 168-87, CrossRef.

Wolkenhauer O, Fell D, De Meyts P, Bluthgen N, Herzel H, Le Novere N, et al. SysBioMed report: advancing systems biology for medical applications. IET Syst Biol. 2009; 3: 131-6, CrossRef.

Hood L, Heath JR, Phelps ME, Lin B. Systems biology and new technologies enable predictive and preventative medicine. Science. 2004; 306: 640-3, CrossRef.

DOI: https://doi.org/10.18585/inabj.v8i3.271

Copyright (c) 2016 The Prodia Education and Research Institute