Yearb Med Inform 2014; 23(01): 199-205
DOI: 10.15265/IY-2014-0015
Original Article
Georg Thieme Verlag KG Stuttgart

Surveying Recent Themes in Translational Bioinformatics: Big Data in EHRs, Omics for Drugs, and Personal Genomics

J. C. Denny
1   Vanderbilt University Medical Center, Departments of Biomedical Informatics and Medicine, Nashville, TN, USA
› Author Affiliations
Further Information

Correspondence to:

Joshua C. Denny, MD, MS
2525 West End Ave - Suite 672
Nashville, TN 37213, USA

Publication History

15 August 2014

Publication Date:
05 March 2018 (online)

 

Summary

Objective: To provide a survey of recent progress in the use of large-scale biologic data to impact clinical care, and the impact the reuse of electronic health record data has made in genomic discovery.

Method: Survey of key themes in translational bioinformatics, primarily from 2012 and 2013.

Result: This survey focuses on four major themes: the growing use of Electronic Health Records (EHRs) as a source for genomic discovery, adoption of genomics and pharmacogenomics in clinical practice, the possible use of genomic technologies for drug repurposing, and the use of personal genomics to guide care.

Conclusion: Reuse of abundant clinical data for research is speeding discovery, and implementation of genomic data into clinical medicine is impacting care with new classes of data rarely used previously in medicine.


#

 


#
  • References

  • 1 Green ED, Guyer MS. Charting a course for genomic medicine from base pairs to bedside.. Nature 2011; Feb 10 470 7333 204-13.
  • 2 International Human Genome Sequencing Consortium.. Finishing the euchromatic sequence of the human genome.. Nature 2004; Oct 21 431 7011 931-45.
  • 3 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; Jun 9 106 (23) 9362-7.
  • 4 OMIM - Online Mendelian Inheritance in Man [Internet].. [cited 2014 May 20].. Available from: http://omim.org
  • 5 Altman RB, Miller KS. 2010 Translational bioinformatics year in review.. J Am Med Inform Assoc 2011; Jul 1 18 (04) 358-66.
  • 6 McCarty CA, Chisholm RL, Chute CG, Kullo IJ, Jarvik GP, Larson EB. et al. The eMERGE Network: A consortium of biorepositories linked to electronic medical records data for conducting genomic studies.. BMC Med Genomics 2011; 4 (01) 13.
  • 7 Gottesman O, Kuivaniemi H, Tromp G, Faucett WA, Li R, Manolio TA. et al. The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future.. Genet Med 2013; 15 (10) 761-71.
  • 8 Denny JC, Ritchie MD, Crawford DC, Schildcrout JS, Ramirez AH, Pulley JM. et al. Identification of genomic predictors of atrioventricular conduction: using electronic medical records as a tool for genome science.. Circulation 2010; Nov 16 122 (20) 2016-21.
  • 9 Kullo IJ, Ding K, Jouni H, Smith CY, Chute CG. A genome-wide association study of red blood cell traits using the electronic medical record.. PloS One [Internet].; 2010. [cited 2010 Oct 29];5(9). Available from: http://www.ncbi.nlm.nih.gov/pubmed/20927387
  • 10 Ritchie MD, Denny JC, Crawford DC, Ramirez AH, Weiner JB, Pulley JM. et al. Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical record.. Am J Hum Genet 2010; Apr 9 86 (04) 560-72.
  • 11 Denny JC, Ritchie MD, Basford MA, Pulley JM, Bastarache L, Brown-Gentry K. et al. PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.. Bioinformatics 2010; May 1 26 (09) 1205-10.
  • 12 Newton KM, Peissig PL, Kho AN, Bielinski SJ, Berg RL, Choudhary V. et al. Validation of electronic medical record-based phenotyping algorithms: results and lessons learned from the eMERGE network.. J Am Med Inform Assoc 2013 Mar 26;
  • 13 Denny JC, Crawford DC, Ritchie MD, Bielinski SJ, Basford MA, Bradford Y. et al. Variants Near FOXE1 Are Associated with Hypothyroidism and Other Thyroid Conditions: Using Electronic Medical Records for Genome- and Phenome-wide Studies.. Am J Hum Genet 2011; Oct 7 89 (04) 529-42.
  • 14 Thompson WK, Rasmussen LV, Pacheco JA, Peissig PL, Denny JC, Kho AN. et al. An evaluation of the NQF Quality Data Model for representing Electronic Health Record driven phenotyping algorithms.. AMIA Annu Symp Proc 2012; 2012: 911-20.
  • 15 Rea S, Pathak J, Savova G, Oniki TA, Westberg L, Beebe CE. et al. Building a robust, scalable and standards-driven infrastructure for secondary use of EHR data: the SHARPn project.. J Biomed Inform 2012; Aug 45 (04) 763-71.
  • 16 Delaney JT, Ramirez AH, Bowton E, Pulley JM, Basford MA, Schildcrout JS. et al. Predicting clopidogrel response using DNA samples linked to an electronic health record.. Clin Pharmacol Ther 2012; Feb 91 (02) 257-63.
  • 17 Xu H, Jiang M, Oetjens M, Bowton EA, Ramirez AH, Jeff JM. et al. Facilitating pharmacogenetic studies using electronic health records and natural-language processing: a case study of warfarin.. J Am Med Inform Assoc 2011; Aug 18 (04) 387-91.
  • 18 Wei W-Q, Feng Q, Jiang L, Waitara MS, Iwuchukwu OF, Roden DM. et al. Characterization of Statin Dose Response in Electronic Medical Records.. Clin Pharmacol Ther [Internet]; 2013. Nov 13 [cited 2013 Dec 31]; Available from: http://www.nature.com/clpt/journal/vaop/ncurrent/full/clpt2013202a.html
  • 19 Wilke RA, Xu H, Denny JC, Roden DM, Krauss RM, McCarty CA. et al. The emerging role of electronic medical records in pharmacogenomics.. Clin Pharmacol Ther 2011; Mar 89 (03) 379-86.
  • 20 Bowton E, Field JR, Wang S, Schildcrout JS, Van Driest SL, Delaney JT. et al. Biobanks and electronic medical records: enabling cost-effective research.. Sci Transl Med 2014; Apr 30 6 (234) 234cm3.
  • 21 Hebbring SJ. The Challenges, Advantages, and Future of Phenome-Wide Association Studies.. Immunology; 2013. Oct 22;
  • 22 Hebbring SJ, Schrodi SJ, Ye Z, Zhou Z, Page D, Brilliant MH. A PheWAS approach in studying HLA-DRB1*1501.. Genes Immun 2013; Apr 14 (03) 187-91.
  • 23 Ritchie MD, Denny JC, Zuvich RL, Crawford DC, Schildcrout JS, Bastarache L. et al. Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk.. Circulation 2013; Apr 2 127 (13) 1377-85.
  • 24 Shameer K, Denny JC, Ding K, Jouni H, Crosslin DR, de Andrade M. et al. A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.. Hum Genet; 2013. Sep 12;
  • 25 Denny JC, Bastarache L, Ritchie MD, Carroll RJ, Zink R, Mosley JD. et al. Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data.. Nat Biotechnol 2013; Nov 24 31 (12) 1102-11.
  • 26 Pendergrass SA, Brown-Gentry K, Dudek S, Frase A, Torstenson ES, Goodloe R. et al. Phenome-wide association study (PheWAS) for detection of pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network.. PLoS Genet 2013; 9 (01) e 1003087.
  • 27 Pendergrass SA, Dudek SM, Crawford DC, Ritchie MD. Visually integrating and exploring high throughput Phenome-Wide Association Study (PheWAS) results using PheWAS-View.. BioData Min 2012; 5 (01) 5.
  • 28 Million Veteran Program (MVP) [Internet].. [cited 2012 Jun 20].. Available from: http://www.research.va.gov/mvp/
  • 29 The Research Program on Genes, Environment, and Health [Internet].. [cited 2014 Jan 2].. Available from: http://www.dor.kaiser.org/external/DORExternal/rpgeh/index.aspx?ekmensel=194f64c3_47_48_btnlink
  • 30 Collins R. What makes UK Biobank special?. Lancet 2012; Mar 31 379 9822 1173-4.
  • 31 Chen Z, Chen J, Collins R, Guo Y, Peto R, Wu F. et al. China Kadoorie Biobank of 0.5 million people: survey methods, baseline characteristics and long-term follow-up.. Int J Epidemiol 2011; Dec 40 (06) 1652-66.
  • 32 LePendu P, Iyer SV, Bauer-Mehren A, Harpaz R, Mortensen JM, Podchiyska T. et al. Pharmacovigilance Using Clinical Notes.. Clin Pharmacol Ther [Internet]; 2013. Apr 10 [cited 2013 Apr 12]; Available from: http://www.nature.com/clpt/journal/vaop/ncurrent/full/clpt201347a.html
  • 33 Leeper NJ, Bauer-Mehren A, Iyer SV, LePendu P, Olson C, Shah NH. Practice-Based Evidence: Profiling the Safety of Cilostazol by Text-Mining of Clinical Notes.. PLoS ONE 2013; May 23 8 (05) e 63499.
  • 34 Ryan PB, Madigan D, Stang PE, Schuemie MJ, Hripcsak G. Medication-Wide Association Studies.. CPT Pharmacomet Syst Pharmacol 2013; Sep 18 2 (09) e76.
  • 35 Frankovich J, Longhurst CA, Sutherland SM. Evidence-Based Medicine in the EMR Era.. N Engl J Med 2011; 365 (19) 1758-9.
  • 36 Liao KP, Kurreeman F, Li G, Duclos G, Murphy S. P RG, et al. Autoantibodies, autoimmune risk alleles and clinical associations in rheumatoid arthritis cases and non-RA controls in the electronic medical records.. Arthritis Rheum; 2012. Dec 10;
  • 37 Neuraz A, Chouchana L, Malamut G, Le Beller C, Roche D, Beaune P. et al. Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics.. PLoS Comput Biol 2013; Dec 26 9 (12) e 1003405.
  • 38 Boland MR, Hripcsak G, Albers DJ, Wei Y, Wilcox AB, Wei J. et al. Discovering medical conditions associated with periodontitis using linked electronic health records.. J Clin Periodontol 2013; May 40 (05) 474-82.
  • 39 Doshi-Velez F, Ge Y, Kohane I. Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis.. Pediatrics; 2013. Dec 9;peds.2013–0819.
  • 40 Blair DR, Lyttle CS, Mortensen JM, Bearden CF, Jensen AB, Khiabanian H. et al. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.. Cell 2013; Sep 26 155 (01) 70-80.
  • 41 Hripcsak G, Albers DJ. Next-generation phenotyping of electronic health records.. J Am Med Inform Assoc 2013; Jan 1 20 (01) 117-21.
  • 42 Weiskopf NG, Hripcsak G, Swaminathan S, Weng C. Defining and measuring completeness of electronic health records for secondary use.. J Biomed Inform 2013; Oct 46 (05) 830-6.
  • 43 Wei W-Q, Leibson CL, Ransom JE, Kho AN, Caraballo PJ, Chai HS. et al. Impact of data fragmentation across healthcare centers on the accuracy of a high-throughput clinical phenotyping algorithm for specifying subjects with type 2 diabetes mellitus.. J Am Med Inform Assoc 2012; Apr 19 (02) 219-24.
  • 44 Collins F. Opportunities and challenges for the NIH--an interview with Francis Collins. Interview by Robert Steinbrook.. N Engl J Med 2009; Oct 1 361 (14) 1321-3.
  • 45 Sarkar IN. Bringing genome tests into clinical practice.. Yearb Med Inform 2013; 8 (01) 172-4.
  • 46 Pulley JM, Denny JC, Peterson JF, Bernard GR, Vnencak-Jones CL, Ramirez AH. et al. Operational Implementation of Prospective Genotyping for Personalized Medicine: The Design of the Vanderbilt PREDICT Project.. Clin Pharmacol Ther 2012; May 16 92 (01) 87-95.
  • 47 Hicks JK, Crews KR, Hoffman JM, Kornegay NM, Wilkinson MR, Lorier R. et al. A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record.. Clin Pharmacol Ther 2012; 92 (05) 563-6.
  • 48 Van Driest SL, Shi Y, Bowton EA, Schildcrout JS, Peterson JF, Pulley J. et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing.. Clin Pharmacol Ther; 2013. Nov 19;
  • 49 O’Donnell PH, Bush A, Spitz J, Danahey K, Saner D, Das S. et al. The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics.. Clin Pharmacol Ther 2012; Oct 92 (04) 446-9.
  • 50 Johnson JA, Elsey AR, Clare-Salzler MJ, Nessl D, Conlon M, Nelson DR. Institutional Profile: University of Florida and Shands Hospital Personalized Medicine Program: clinical implementation of pharmacogenetics.. Pharmacogenomics 2013; May 14 (07) 723-6.
  • 51 Gottesman O, Scott SA, Ellis SB, Overby CL, Ludtke A, Hulot J-S. et al. The CLIPMERGE PGx Program: clinical implementation of personalized medicine through electronic health records and genomics-pharmacogenomics.. Clin Pharmacol Ther 2013; Aug 94 (02) 214-7.
  • 52 Implementing Genomics in Practice (IGNITE) [Internet].. [cited 2014 Jan 9].. Available from: http://www.genome.gov/27554264
  • 53 Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network.. Clin Pharmacol Ther 2011; Mar 89 (03) 464-7.
  • 54 List Dosing Guidelines [PharmGKB] [Internet].. [cited 2014 Jan 9].. Available from: http://www.pharmgkb.org/view/dosing-guidelines.do?-source=CPIC
  • 55 Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot J-S, Johnson JA. et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy.. Clin Pharmacol Ther 2011; Aug 90 (02) 328-32.
  • 56 Scott SA, Sangkuhl K, Stein CM, Hulot J-S, Mega JL, Roden DM. et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.. Clin Pharmacol Ther 2013; Sep 94 (03) 317-23.
  • 57 Pharmacogenomic Biomarkers in Drug Labels [Internet].. [cited 2011 Mar 9].. Available from: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm
  • 58 Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical R&D efficiency.. Nat Rev Drug Discov 2012; Mar 11 (03) 191-200.
  • 59 Dudley JT, Sirota M, Shenoy M, Pai RK, Roedder S, Chiang AP. et al. Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease.. Sci Transl Med 2011; Aug 17 3 (96) 96 ra76.
  • 60 Sirota M, Dudley JT, Kim J, Chiang AP, Morgan AA, Sweet-Cordero A. et al. Discovery and preclinical validation of drug indications using compendia of public gene expression data.. Sci Transl Med 2011; Aug 17 3 (96) 96 ra77.
  • 61 Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ. et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.. Science 2006; Sep 29 313 5795 1929-35.
  • 62 Jahchan NS, Dudley JT, Mazur PK, Flores N, Yang D, Palmerton A. et al. A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors.. Cancer Discov 2013; Dec 3 (12) 1364-77.
  • 63 Sanseau P, Agarwal P, Barnes MR, Pastinen T, Richards JB, Cardon LR. et al. Use of genome-wide association studies for drug repositioning.. Nat Biotechnol 2012; Apr 30 (04) 317-20.
  • 64 Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery.. Nature [Internet] 2013. Dec 25 [cited 2013 Dec 28]; advance online publication.; Available from: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12873.html
  • 65 Khatri P, Roedder S, Kimura N, De Vusser K, Morgan AA, Gong Y. et al. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.. J Exp Med 2013; Oct 21 210 (11) 2205-21.
  • 66 Sateriale A, Bessoff K, Sarkar IN, Huston CD. Drug repurposing: mining protozoan proteomes for targets of known bioactive compounds.. J Am Med Inform Assoc 2013 Jun 11;
  • 67 Griffith M, Griffith OL, Coffman AC, Weible JV, McMichael JF, Spies NC. et al. DGIdb: mining the druggable genome.. Nat Methods 2013; Dec 10 (12) 1209-10.
  • 68 Tenenbaum J, James A, Paulyson-Nuñez K. An Altered Treatment Plan Based on Direct to Consumer (DTC) Genetic Testing: Personalized Medicine from the Patient/Pin-cushion Perspective.. J Pers Med 2012; Oct 30 2 (04) 192-200.
  • 69 Kalf RRJ, Mihaescu R, Kundu S, de Knijff P, Green RC, Janssens ACJW. Variations in predicted risks in personal genome testing for common complex diseases.. Genet Med [Internet] 2013 Jun 27 [cited 2013 Dec 27]; Available from: http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201380a.html
  • 70 Tung JY, Do CB, Hinds DA, Kiefer AK, Macpherson JM, Chowdry AB. et al. Efficient replication of over 180 genetic associations with self-reported medical data.. PloS One 2011; 6 (08) e23473.
  • 71 Hinds DA, McMahon G, Kiefer AK, Do CB, Eriksson N, Evans DM. et al. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.. Nat Genet 2013; Aug 45 (08) 907-11.
  • 72 Eriksson N, Tung JY, Kiefer AK, Hinds DA, Fran-cke U, Mountain JL. et al. Novel associations for hypothyroidism include known autoimmune risk loci.. PloS One 2012; 7 (04) e 34442.
  • 73 2013 - 23andMe, Inc. 11/22/13 [Internet].. [cited 2013 Dec 27]. Available from: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm376296.htm
  • 74 Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HYK, Chen R. et al. Personal omics profiling reveals dynamic molecular and medical phenotypes.. Cell 2012; Mar 16 148 (06) 1293-307.
  • 75 Lovly CM, Dahlman KB, Fohn LE, Su Z, Dias-Santagata D, Hicks DJ. et al. Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials.. PloS One 2012; 7 (04) e 35309.
  • 76 Dahlman KB, Xia J, Hutchinson K, Ng C, Hucks D, Jia P. et al. BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors.. Cancer Discov 2012; Sep 2 (09) 791-7.
  • 77 Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP. et al. BRAF mutations in hairy-cell leukemia.. N Engl J Med 2011; Jun 16 364 (24) 2305-15.
  • 78 Hairy Cell Leukemia—New Genes, New Targets - Springer.. [cited 2014 Jan 4]; Available from: http://link.springer.com/article/10.1007%2Fs11899-013-0167-0/fulltext.html#Sec17
  • 79 Ciriello G, Miller ML, Aksoy BA, Senbabaoglu Y, Schultz N, Sander C. Emerging landscape of oncogenic signatures across human cancers.. Nat Genet 2013; Oct 45 (10) 1127-33.
  • 80 Cancer Genome Atlas Network.. Comprehensive molecular portraits of human breast tumours.. Nature 2012; Oct 4 490 7418 61-70.
  • 81 Snitkin ES, Zelazny AM, Thomas PJ, Stock F. NISC Comparative Sequencing Program Group,. Henderson DK. et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing.. Sci Transl Med 2012; Aug 22 4 (148) 148 ra116.
  • 82 Chin C-S, Sorenson J, Harris JB, Robins WP, Charles RC, Jean-Charles RR. et al. The Origin of the Haitian Cholera Outbreak Strain.. N Engl J Med 2011; Jan 6 364 (01) 33-42.
  • 83 Hasan NA, Choi SY, Eppinger M, Clark PW, Chen A, Alam M. et al. Genomic diversity of 2010 Haitian cholera outbreak strains.. Proc Natl Acad Sci U S A 2012; Jul 17 109 (29) E2010-2017.
  • 84 Starren J, Williams MS, Bottinger EP. Crossing the omic chasm: a time for omic ancillary systems.. JAMA J Am Med Assoc 2013; Mar 27 309 (12) 1237-8.

Correspondence to:

Joshua C. Denny, MD, MS
2525 West End Ave - Suite 672
Nashville, TN 37213, USA

  • References

  • 1 Green ED, Guyer MS. Charting a course for genomic medicine from base pairs to bedside.. Nature 2011; Feb 10 470 7333 204-13.
  • 2 International Human Genome Sequencing Consortium.. Finishing the euchromatic sequence of the human genome.. Nature 2004; Oct 21 431 7011 931-45.
  • 3 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; Jun 9 106 (23) 9362-7.
  • 4 OMIM - Online Mendelian Inheritance in Man [Internet].. [cited 2014 May 20].. Available from: http://omim.org
  • 5 Altman RB, Miller KS. 2010 Translational bioinformatics year in review.. J Am Med Inform Assoc 2011; Jul 1 18 (04) 358-66.
  • 6 McCarty CA, Chisholm RL, Chute CG, Kullo IJ, Jarvik GP, Larson EB. et al. The eMERGE Network: A consortium of biorepositories linked to electronic medical records data for conducting genomic studies.. BMC Med Genomics 2011; 4 (01) 13.
  • 7 Gottesman O, Kuivaniemi H, Tromp G, Faucett WA, Li R, Manolio TA. et al. The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future.. Genet Med 2013; 15 (10) 761-71.
  • 8 Denny JC, Ritchie MD, Crawford DC, Schildcrout JS, Ramirez AH, Pulley JM. et al. Identification of genomic predictors of atrioventricular conduction: using electronic medical records as a tool for genome science.. Circulation 2010; Nov 16 122 (20) 2016-21.
  • 9 Kullo IJ, Ding K, Jouni H, Smith CY, Chute CG. A genome-wide association study of red blood cell traits using the electronic medical record.. PloS One [Internet].; 2010. [cited 2010 Oct 29];5(9). Available from: http://www.ncbi.nlm.nih.gov/pubmed/20927387
  • 10 Ritchie MD, Denny JC, Crawford DC, Ramirez AH, Weiner JB, Pulley JM. et al. Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical record.. Am J Hum Genet 2010; Apr 9 86 (04) 560-72.
  • 11 Denny JC, Ritchie MD, Basford MA, Pulley JM, Bastarache L, Brown-Gentry K. et al. PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.. Bioinformatics 2010; May 1 26 (09) 1205-10.
  • 12 Newton KM, Peissig PL, Kho AN, Bielinski SJ, Berg RL, Choudhary V. et al. Validation of electronic medical record-based phenotyping algorithms: results and lessons learned from the eMERGE network.. J Am Med Inform Assoc 2013 Mar 26;
  • 13 Denny JC, Crawford DC, Ritchie MD, Bielinski SJ, Basford MA, Bradford Y. et al. Variants Near FOXE1 Are Associated with Hypothyroidism and Other Thyroid Conditions: Using Electronic Medical Records for Genome- and Phenome-wide Studies.. Am J Hum Genet 2011; Oct 7 89 (04) 529-42.
  • 14 Thompson WK, Rasmussen LV, Pacheco JA, Peissig PL, Denny JC, Kho AN. et al. An evaluation of the NQF Quality Data Model for representing Electronic Health Record driven phenotyping algorithms.. AMIA Annu Symp Proc 2012; 2012: 911-20.
  • 15 Rea S, Pathak J, Savova G, Oniki TA, Westberg L, Beebe CE. et al. Building a robust, scalable and standards-driven infrastructure for secondary use of EHR data: the SHARPn project.. J Biomed Inform 2012; Aug 45 (04) 763-71.
  • 16 Delaney JT, Ramirez AH, Bowton E, Pulley JM, Basford MA, Schildcrout JS. et al. Predicting clopidogrel response using DNA samples linked to an electronic health record.. Clin Pharmacol Ther 2012; Feb 91 (02) 257-63.
  • 17 Xu H, Jiang M, Oetjens M, Bowton EA, Ramirez AH, Jeff JM. et al. Facilitating pharmacogenetic studies using electronic health records and natural-language processing: a case study of warfarin.. J Am Med Inform Assoc 2011; Aug 18 (04) 387-91.
  • 18 Wei W-Q, Feng Q, Jiang L, Waitara MS, Iwuchukwu OF, Roden DM. et al. Characterization of Statin Dose Response in Electronic Medical Records.. Clin Pharmacol Ther [Internet]; 2013. Nov 13 [cited 2013 Dec 31]; Available from: http://www.nature.com/clpt/journal/vaop/ncurrent/full/clpt2013202a.html
  • 19 Wilke RA, Xu H, Denny JC, Roden DM, Krauss RM, McCarty CA. et al. The emerging role of electronic medical records in pharmacogenomics.. Clin Pharmacol Ther 2011; Mar 89 (03) 379-86.
  • 20 Bowton E, Field JR, Wang S, Schildcrout JS, Van Driest SL, Delaney JT. et al. Biobanks and electronic medical records: enabling cost-effective research.. Sci Transl Med 2014; Apr 30 6 (234) 234cm3.
  • 21 Hebbring SJ. The Challenges, Advantages, and Future of Phenome-Wide Association Studies.. Immunology; 2013. Oct 22;
  • 22 Hebbring SJ, Schrodi SJ, Ye Z, Zhou Z, Page D, Brilliant MH. A PheWAS approach in studying HLA-DRB1*1501.. Genes Immun 2013; Apr 14 (03) 187-91.
  • 23 Ritchie MD, Denny JC, Zuvich RL, Crawford DC, Schildcrout JS, Bastarache L. et al. Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk.. Circulation 2013; Apr 2 127 (13) 1377-85.
  • 24 Shameer K, Denny JC, Ding K, Jouni H, Crosslin DR, de Andrade M. et al. A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.. Hum Genet; 2013. Sep 12;
  • 25 Denny JC, Bastarache L, Ritchie MD, Carroll RJ, Zink R, Mosley JD. et al. Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data.. Nat Biotechnol 2013; Nov 24 31 (12) 1102-11.
  • 26 Pendergrass SA, Brown-Gentry K, Dudek S, Frase A, Torstenson ES, Goodloe R. et al. Phenome-wide association study (PheWAS) for detection of pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network.. PLoS Genet 2013; 9 (01) e 1003087.
  • 27 Pendergrass SA, Dudek SM, Crawford DC, Ritchie MD. Visually integrating and exploring high throughput Phenome-Wide Association Study (PheWAS) results using PheWAS-View.. BioData Min 2012; 5 (01) 5.
  • 28 Million Veteran Program (MVP) [Internet].. [cited 2012 Jun 20].. Available from: http://www.research.va.gov/mvp/
  • 29 The Research Program on Genes, Environment, and Health [Internet].. [cited 2014 Jan 2].. Available from: http://www.dor.kaiser.org/external/DORExternal/rpgeh/index.aspx?ekmensel=194f64c3_47_48_btnlink
  • 30 Collins R. What makes UK Biobank special?. Lancet 2012; Mar 31 379 9822 1173-4.
  • 31 Chen Z, Chen J, Collins R, Guo Y, Peto R, Wu F. et al. China Kadoorie Biobank of 0.5 million people: survey methods, baseline characteristics and long-term follow-up.. Int J Epidemiol 2011; Dec 40 (06) 1652-66.
  • 32 LePendu P, Iyer SV, Bauer-Mehren A, Harpaz R, Mortensen JM, Podchiyska T. et al. Pharmacovigilance Using Clinical Notes.. Clin Pharmacol Ther [Internet]; 2013. Apr 10 [cited 2013 Apr 12]; Available from: http://www.nature.com/clpt/journal/vaop/ncurrent/full/clpt201347a.html
  • 33 Leeper NJ, Bauer-Mehren A, Iyer SV, LePendu P, Olson C, Shah NH. Practice-Based Evidence: Profiling the Safety of Cilostazol by Text-Mining of Clinical Notes.. PLoS ONE 2013; May 23 8 (05) e 63499.
  • 34 Ryan PB, Madigan D, Stang PE, Schuemie MJ, Hripcsak G. Medication-Wide Association Studies.. CPT Pharmacomet Syst Pharmacol 2013; Sep 18 2 (09) e76.
  • 35 Frankovich J, Longhurst CA, Sutherland SM. Evidence-Based Medicine in the EMR Era.. N Engl J Med 2011; 365 (19) 1758-9.
  • 36 Liao KP, Kurreeman F, Li G, Duclos G, Murphy S. P RG, et al. Autoantibodies, autoimmune risk alleles and clinical associations in rheumatoid arthritis cases and non-RA controls in the electronic medical records.. Arthritis Rheum; 2012. Dec 10;
  • 37 Neuraz A, Chouchana L, Malamut G, Le Beller C, Roche D, Beaune P. et al. Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics.. PLoS Comput Biol 2013; Dec 26 9 (12) e 1003405.
  • 38 Boland MR, Hripcsak G, Albers DJ, Wei Y, Wilcox AB, Wei J. et al. Discovering medical conditions associated with periodontitis using linked electronic health records.. J Clin Periodontol 2013; May 40 (05) 474-82.
  • 39 Doshi-Velez F, Ge Y, Kohane I. Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis.. Pediatrics; 2013. Dec 9;peds.2013–0819.
  • 40 Blair DR, Lyttle CS, Mortensen JM, Bearden CF, Jensen AB, Khiabanian H. et al. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.. Cell 2013; Sep 26 155 (01) 70-80.
  • 41 Hripcsak G, Albers DJ. Next-generation phenotyping of electronic health records.. J Am Med Inform Assoc 2013; Jan 1 20 (01) 117-21.
  • 42 Weiskopf NG, Hripcsak G, Swaminathan S, Weng C. Defining and measuring completeness of electronic health records for secondary use.. J Biomed Inform 2013; Oct 46 (05) 830-6.
  • 43 Wei W-Q, Leibson CL, Ransom JE, Kho AN, Caraballo PJ, Chai HS. et al. Impact of data fragmentation across healthcare centers on the accuracy of a high-throughput clinical phenotyping algorithm for specifying subjects with type 2 diabetes mellitus.. J Am Med Inform Assoc 2012; Apr 19 (02) 219-24.
  • 44 Collins F. Opportunities and challenges for the NIH--an interview with Francis Collins. Interview by Robert Steinbrook.. N Engl J Med 2009; Oct 1 361 (14) 1321-3.
  • 45 Sarkar IN. Bringing genome tests into clinical practice.. Yearb Med Inform 2013; 8 (01) 172-4.
  • 46 Pulley JM, Denny JC, Peterson JF, Bernard GR, Vnencak-Jones CL, Ramirez AH. et al. Operational Implementation of Prospective Genotyping for Personalized Medicine: The Design of the Vanderbilt PREDICT Project.. Clin Pharmacol Ther 2012; May 16 92 (01) 87-95.
  • 47 Hicks JK, Crews KR, Hoffman JM, Kornegay NM, Wilkinson MR, Lorier R. et al. A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record.. Clin Pharmacol Ther 2012; 92 (05) 563-6.
  • 48 Van Driest SL, Shi Y, Bowton EA, Schildcrout JS, Peterson JF, Pulley J. et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing.. Clin Pharmacol Ther; 2013. Nov 19;
  • 49 O’Donnell PH, Bush A, Spitz J, Danahey K, Saner D, Das S. et al. The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics.. Clin Pharmacol Ther 2012; Oct 92 (04) 446-9.
  • 50 Johnson JA, Elsey AR, Clare-Salzler MJ, Nessl D, Conlon M, Nelson DR. Institutional Profile: University of Florida and Shands Hospital Personalized Medicine Program: clinical implementation of pharmacogenetics.. Pharmacogenomics 2013; May 14 (07) 723-6.
  • 51 Gottesman O, Scott SA, Ellis SB, Overby CL, Ludtke A, Hulot J-S. et al. The CLIPMERGE PGx Program: clinical implementation of personalized medicine through electronic health records and genomics-pharmacogenomics.. Clin Pharmacol Ther 2013; Aug 94 (02) 214-7.
  • 52 Implementing Genomics in Practice (IGNITE) [Internet].. [cited 2014 Jan 9].. Available from: http://www.genome.gov/27554264
  • 53 Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network.. Clin Pharmacol Ther 2011; Mar 89 (03) 464-7.
  • 54 List Dosing Guidelines [PharmGKB] [Internet].. [cited 2014 Jan 9].. Available from: http://www.pharmgkb.org/view/dosing-guidelines.do?-source=CPIC
  • 55 Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot J-S, Johnson JA. et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy.. Clin Pharmacol Ther 2011; Aug 90 (02) 328-32.
  • 56 Scott SA, Sangkuhl K, Stein CM, Hulot J-S, Mega JL, Roden DM. et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.. Clin Pharmacol Ther 2013; Sep 94 (03) 317-23.
  • 57 Pharmacogenomic Biomarkers in Drug Labels [Internet].. [cited 2011 Mar 9].. Available from: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm
  • 58 Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical R&D efficiency.. Nat Rev Drug Discov 2012; Mar 11 (03) 191-200.
  • 59 Dudley JT, Sirota M, Shenoy M, Pai RK, Roedder S, Chiang AP. et al. Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease.. Sci Transl Med 2011; Aug 17 3 (96) 96 ra76.
  • 60 Sirota M, Dudley JT, Kim J, Chiang AP, Morgan AA, Sweet-Cordero A. et al. Discovery and preclinical validation of drug indications using compendia of public gene expression data.. Sci Transl Med 2011; Aug 17 3 (96) 96 ra77.
  • 61 Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ. et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.. Science 2006; Sep 29 313 5795 1929-35.
  • 62 Jahchan NS, Dudley JT, Mazur PK, Flores N, Yang D, Palmerton A. et al. A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors.. Cancer Discov 2013; Dec 3 (12) 1364-77.
  • 63 Sanseau P, Agarwal P, Barnes MR, Pastinen T, Richards JB, Cardon LR. et al. Use of genome-wide association studies for drug repositioning.. Nat Biotechnol 2012; Apr 30 (04) 317-20.
  • 64 Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery.. Nature [Internet] 2013. Dec 25 [cited 2013 Dec 28]; advance online publication.; Available from: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12873.html
  • 65 Khatri P, Roedder S, Kimura N, De Vusser K, Morgan AA, Gong Y. et al. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.. J Exp Med 2013; Oct 21 210 (11) 2205-21.
  • 66 Sateriale A, Bessoff K, Sarkar IN, Huston CD. Drug repurposing: mining protozoan proteomes for targets of known bioactive compounds.. J Am Med Inform Assoc 2013 Jun 11;
  • 67 Griffith M, Griffith OL, Coffman AC, Weible JV, McMichael JF, Spies NC. et al. DGIdb: mining the druggable genome.. Nat Methods 2013; Dec 10 (12) 1209-10.
  • 68 Tenenbaum J, James A, Paulyson-Nuñez K. An Altered Treatment Plan Based on Direct to Consumer (DTC) Genetic Testing: Personalized Medicine from the Patient/Pin-cushion Perspective.. J Pers Med 2012; Oct 30 2 (04) 192-200.
  • 69 Kalf RRJ, Mihaescu R, Kundu S, de Knijff P, Green RC, Janssens ACJW. Variations in predicted risks in personal genome testing for common complex diseases.. Genet Med [Internet] 2013 Jun 27 [cited 2013 Dec 27]; Available from: http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201380a.html
  • 70 Tung JY, Do CB, Hinds DA, Kiefer AK, Macpherson JM, Chowdry AB. et al. Efficient replication of over 180 genetic associations with self-reported medical data.. PloS One 2011; 6 (08) e23473.
  • 71 Hinds DA, McMahon G, Kiefer AK, Do CB, Eriksson N, Evans DM. et al. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.. Nat Genet 2013; Aug 45 (08) 907-11.
  • 72 Eriksson N, Tung JY, Kiefer AK, Hinds DA, Fran-cke U, Mountain JL. et al. Novel associations for hypothyroidism include known autoimmune risk loci.. PloS One 2012; 7 (04) e 34442.
  • 73 2013 - 23andMe, Inc. 11/22/13 [Internet].. [cited 2013 Dec 27]. Available from: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm376296.htm
  • 74 Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HYK, Chen R. et al. Personal omics profiling reveals dynamic molecular and medical phenotypes.. Cell 2012; Mar 16 148 (06) 1293-307.
  • 75 Lovly CM, Dahlman KB, Fohn LE, Su Z, Dias-Santagata D, Hicks DJ. et al. Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials.. PloS One 2012; 7 (04) e 35309.
  • 76 Dahlman KB, Xia J, Hutchinson K, Ng C, Hucks D, Jia P. et al. BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors.. Cancer Discov 2012; Sep 2 (09) 791-7.
  • 77 Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP. et al. BRAF mutations in hairy-cell leukemia.. N Engl J Med 2011; Jun 16 364 (24) 2305-15.
  • 78 Hairy Cell Leukemia—New Genes, New Targets - Springer.. [cited 2014 Jan 4]; Available from: http://link.springer.com/article/10.1007%2Fs11899-013-0167-0/fulltext.html#Sec17
  • 79 Ciriello G, Miller ML, Aksoy BA, Senbabaoglu Y, Schultz N, Sander C. Emerging landscape of oncogenic signatures across human cancers.. Nat Genet 2013; Oct 45 (10) 1127-33.
  • 80 Cancer Genome Atlas Network.. Comprehensive molecular portraits of human breast tumours.. Nature 2012; Oct 4 490 7418 61-70.
  • 81 Snitkin ES, Zelazny AM, Thomas PJ, Stock F. NISC Comparative Sequencing Program Group,. Henderson DK. et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing.. Sci Transl Med 2012; Aug 22 4 (148) 148 ra116.
  • 82 Chin C-S, Sorenson J, Harris JB, Robins WP, Charles RC, Jean-Charles RR. et al. The Origin of the Haitian Cholera Outbreak Strain.. N Engl J Med 2011; Jan 6 364 (01) 33-42.
  • 83 Hasan NA, Choi SY, Eppinger M, Clark PW, Chen A, Alam M. et al. Genomic diversity of 2010 Haitian cholera outbreak strains.. Proc Natl Acad Sci U S A 2012; Jul 17 109 (29) E2010-2017.
  • 84 Starren J, Williams MS, Bottinger EP. Crossing the omic chasm: a time for omic ancillary systems.. JAMA J Am Med Assoc 2013; Mar 27 309 (12) 1237-8.