Deeper, longer phenotyping to accelerate the discovery of the genetic architectures of diseases

National Research Council: Toward Precision Medicine : Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. 2011, Washington, DC: The National Academies Press Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF: The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007, 356: 217-226. 10.1056/NEJMoa063994. Raponi M, Dossey L, Jatkoe T, Wu X, Chen G, Fan H, Beer DG: MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res. 2009, 69: 5776-5783. 10.1158/0008-5472.CAN-09-0587. Kang H, Chen IM, Wilson CS, Bedrick EJ, Harvey RC, Atlas SR, Devidas M, Mullighan CG, Wang X, Murphy M, Ar K, Wharton W, Borowitz MJ, Bowman WP, Bhojwani D, Carroll WL, Camitta BM, Reaman GH, Smith MA, Downing JR, Hunger SP, Willman CL: Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood. 2010, 115: 1394-1405. 10.1182/blood-2009-05-218560. Butte AJ, Kohane IS: Creation and implications of a phenome-genome network. Nat Biotechnol. 2006, 24: 55-62. 10.1038/nbt1150. Loscalzo J, Kohane I, Barabasi AL: Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol Syst Biol. 2007, 3: 124- Roberts NJ, Vogelstein JT, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE: The predictive capacity of personal genome sequencing. Sci Transl Med. 2012, 4: 133ra158- Stessman HA, Bernier R, Eichler EE: A genotype-first approach to defining the subtypes of a complex disease. Cell. 2014, 156: 872-877. 10.1016/j.cell.2014.02.002. Frayling TM, Lindgren CM, Chevre JC, Menzel S, Wishart M, Benmezroua Y, Brown A, Evans JC, Rao PS, Dina C, Lecoeur C, Kanninen T, Almgren P, Bulman MP, Wang Y, Mills J, Wright-Pascoe R, Mahtani MM, Prisco F, Costa A, Cognet I, Hansen T, Pedersen O, Ellard S, Tuomi T, Groop LC, Froguel P, Hattersley AT, Vaxillaire M: A genome-wide scan in families with maturity-onset diabetes of the young: evidence for further genetic heterogeneity. Diabetes. 2003, 52: 872-881. 10.2337/diabetes.52.3.872. Steinthorsdottir V, Thorleifsson G, Sulem P, Helgason H, Grarup N, Sigurdsson A, Helgadottir HT, Johannsdottir H, Magnusson OT, Gudjonsson SA, Justesen JM, Harder MN, Jørgensen ME, Christensen C, Brandslund I, Sandbæk A, Lauritzen T, Vestergaard H, Linneberg A, Jørgensen T, Hansen T, Daneshpour MS, Fallah MS, Hreidarsson AB, Sigurdsson G, Azizi F, Benediktsson R, Masson G, Helgason A, Kong A, et al: Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nat Genet. 2014, 46: 294-298. 10.1038/ng.2882. Betancur C: Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting. Brain Res. 2011, 1380: 42-77. Van Bokhoven H: Genetic and epigenetic networks in intellectual disabilities. Annu Rev Genet. 2011, 45: 81-104. 10.1146/annurev-genet-110410-132512. Campbell MG, Kohane IS, Kong SW: Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome. BMC Med Genomics. 2013, 6: 34-10.1186/1755-8794-6-34. Purcell S, Cherny SS, Sham PC: Genetic power calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics. 2003, 19: 149-150. 10.1093/bioinformatics/19.1.149. Deary IJ, Yang J, Davies G, Harris SE, Tenesa A, Liewald D, Luciano M, Lopez LM, Gow AJ, Corley J, Redmond P, Fox HC, Rowe SJ, Haggarty P, McNeill G, Goddard ME, Porteous DJ, Whalley LJ, Starr JM, Visscher PM: Genetic contributions to stability and change in intelligence from childhood to old age. Nature. 2012, 482: 212-215. Ingelsson E, Langenberg C, Hivert MF, Prokopenko I, Lyssenko V, Dupuis J, Mägi R, Sharp S, Jackson AU, Assimes TL, Shrader P, Knowles JW, Zethelius B, Abbasi FA, Bergman RN, Bergmann A, Berne C, Boehnke M, Bonnycastle LL, Bornstein SR, Buchanan TA, Bumpstead SJ, Böttcher Y, Chines P, Collins FS, Cooper CC, Dennison EM, Erdos MR, Ferrannini E, Fox CS: Detailed physiologic characterization reveals diverse mechanisms for novel genetic loci regulating glucose and insulin metabolism in humans. Diabetes. 2010, 59: 1266-1275. 10.2337/db09-1568. Howrylak JA, Fuglbrigge AL, Strunk RC, Zeiger RS, Weiss ST, Raby BA: Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications. J Allergy Clin Immunol. 2014, 133: 1289-1300. 10.1016/j.jaci.2014.02.006. Murphy S, Churchill S, Bry L, Chueh H, Weiss S, Lazarus R, Zeng Q, Dubey A, Gainer V, Mendis M, Glaser J, Kohane I: Instrumenting the health care enterprise for discovery research in the genomic era. Genome Res. 2009, 19: 1675-1681. 10.1101/gr.094615.109. Kohane IS: Using electronic health records to drive discovery in disease genomics. Nat Rev Genet. 2011, 12: 417-428. 10.1038/nrg2999. Ananthakrishnan AN, Cai T, Savova G, Cheng SC, Chen P, Perez RG, Gainer VS, Murphy SN, Szolovits P, Xia Z, Shaw S, Churchill S, Karlson EW, Kohane I, Plenge RM, Liao KP: Improving case definition of Crohn's disease and ulcerative colitis in electronic medical records using natural language processing: a novel informatics approach. Inflamm Bowel Dis. 2013, 19: 1411-1420. 10.1097/MIB.0b013e31828133fd. Meystre S, Haug PJ: Natural language processing to extract medical problems from electronic clinical documents: Performance evaluation. J Biomed Inform. 2006, 39: 589-599. 10.1016/j.jbi.2005.11.004. Doshi-Velez F, Ge Y, Kohane I: Comorbidity clusters in autism spectrum disorders: an electronic health record time-series analysis. Pediatrics. 2014, 133: e54-e63. 10.1542/peds.2013-0819.