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Appendix E Glossary Biobank a bank of biological specimens for biomedical research. Biomarker a characteristic that is objectively measured and evaluated as an in - dicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention (IOM 2010a). Biosamples Samples of biological materials Candidate gene a gene whose chromosomal location is associated with a par- ticular disease or other phenotype. Because of its location, the gene is suspected of causing the disease or other phenotype (NHGRI 2011). Chromosomal translocation a condition where a fragment of one chromosome is broken off and is then attached to another. Depending on which piece of chromosome is moved to where, this results in a wide range of medical prob - lems, such as leukemia, breast cancer, schizophrenia, or muscular dystrophy (USC 2011). Clinical utility the ability of a screening or diagnostic test to prevent or amelio - rate adverse health outcomes such as mortality, morbidity, or disability through the adoption of efficacious treatments conditioned on test results (Khoury 2003). Crowd sourcing informal reports of large groups of people Database of Genotypes and Phenotypes (dbGap) developed to archive and distribute the results of studies that have investigated the interaction of geno - type and phenotype (NCBI 2011). 119

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120 APPENDIX E Data-intensive biology understanding of biological processes through models and algorithms of mathematics, statistics, and computer science using the vast volumes of data generated by new technologies (http://sc11.supercomputing. org/schedule/event_detail.php?evid=wksp120). Decision-support systems a specific class of computerized information system that supports business and organizational decision-making activities (Informa - tion Builders 2011). Disease marker specific molecular signature of disease, physiological measure- ment, genotype structural or functional characteristic, metabolic changes, or other determinant that may simplify the diagnostic process, make diagnoses more accurate, distinguish different causes of disease, or enable physicians to make diagnoses before symptoms appear and to track disease progression (Medical Dictionary 2011) Disease risk the probability that an individual who is initially disease-free will developed given disease over specified time or age interval (e.g. one year or lifetime) (Pigeot 2005). Disease taxonomy the science of disease classification. DNA (Deoxyribonucleic acid) the polymer that encodes genetic material and therefore the structures of proteins and many animal traits. EHR (Electronic Health Record) a subset of each CDO’s EMR, presently assumed to include summaries, such as ASTM’s Continuity of Care Record (CCR) and HL7’s Care Record Summary (CRS), and possibly information from pharmacy benefit management firms, reference labs and other organizations about the health status of patients in the community (Garets and Davis 2005). EHR-derived phenotype phenotype based on Electronic Health Record (EHR). Electronic medical records (EMS) computerized legal clinical records created in CDOs, such as hospitals and physician offices (Garets and Davis 2005). Epigenetic relating to, being, or involving a modification in gene expression that is independent of the DNA sequence of a gene (e.g., epigenetic carcino- genesis, epigenetic inheritance) (Merriam-Webster 2007). Epigenome the epigenome consists of chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it, and when to do it. Different cells have different epigenetic marks. These epigenetic marks, which are not part of the DNA itself, can be passed on from cell to cell as cells divide, and from one generation to the next (NHGRI 2011). Epiphenomenon an additional condition or symptom in the course of a disease, not necessarily connected with the disease (Houghton Mifflin Company 2007).

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121 APPENDIX E Etiology the study of all factors that may be involved in the development of a disease, including the susceptibility of the patient, the nature of the disease agent, and the way in which the patient’s body is invaded by the agent (Mosby 2009). Exposome characterization of both exogenous and endogenous exposures that can have differential effects at various stages during a person’s lifetime (Wild 2005; Rappaport 2011). Gel electrophoresis electrophoresis in which molecules (as proteins and nucleic acids) migrate through a gel and especially a polyacrylamide gel and separate into bands according to size (Merriam-Webster 2007). GenBank the GenBank sequence database is an annotated collection of all publicly available nucleotide sequences and their protein translations (Mizrachi 2002). Gene-environment interactions an influence on the expression of a trait that results from the interplay between genes and the environment. Some traits are strongly influenced by genes, while other traits are strongly influenced by the environment. Most traits, however, are influenced by one or more genes inter- acting in complex ways with the environment (NHGRI 2011). Gene expression is the process by which the information encoded in a gene is used to direct the assembly of a protein molecule. The cell reads the sequence of the gene in groups of three bases. Each group of three bases (codon) cor- responds to one of 20 different amino acids used to build the protein (NHGRI 2011). Gene expression profiling is the measurement of the activity of thousands of genes at once to create a global picture of cellular function. These profiles can, for example, distinguish between cells that are actively dividing, or show how the cells react to a particular treatment. Many experiments of this sort measure an entire genome simultaneously, that is, every gene present in a particular cell (InfoGlobalLink 2011). Genetic polymorphisms the recurrence within a population of two or more discontinuous genetic variants of a specific trait in such proportions that they cannot be maintained simply by mutation. Examples include the sickle cell trait, the Rh factor, and the blood groups (Mosby 2009). Genetic privacy the protection of genetic information about an individual, family, or population group from unauthorized disclosure (Kahn and Ninomiya 2010). Genome the full sequence of genetic material encoded in DNA in an organism.

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122 APPENDIX E Genome-Wide Association Study (GWAS) a study that identifies markers across genomes to find genetic variation associated with a disease or condition (PCAST 2008). Genotype the genetic sequence of an individual organism, often categorized in terms of known genetic variants. This can either refer to known alleles (or types) of a single gene or to collections of genes. For example, some lung cancers have a mutant Egf receptor genotype while other lung cancers have a wild-type (or normal) Egf receptor genotype. Geographic Information System (GIS) an organized collection of computer hardware, software, geographic data, and personnel designed to efficiently cap- ture, store, update, manipulate, analyze, and display all forms of geographically referenced information (ESRI 1990). Health Insurance Portability and Accountability Act (HIPAA) an act of Con- gress, passed in 1996, that affords certain protections to persons covered by health-care plans, including continuity of coverage when changing jobs, stan - dards for electronic health-care transactions, and privacy safeguards for indi - vidually identifiable patient information (Mosby 2009). Heterozygous having inherited different forms of a particular gene from each parent. A heterozygous genotype stands in contrast to a homozygous genotype, where an individual inherits identical forms of a particular gene from each par- ent (NHGRI 2011). Histology the science dealing with the microscopic identification of cells and tissue (Mosby 2009). Human Microbiome Project (HMP) a National Institutes of Health initiative that aims to characterize the microbial communities found at several different sites on the human body, including nasal passages, oral cavities, skin, gastroin - testinal tract, and urogenital tract, and to analyze the role of these microbes in human health and disease. Institutional Review Board (IRB) a group of physicians, scientists, ethicists, lawyers, and community members that review human subjects research to ensure that the research will be performed ethically and that it will benefit patients. Individual institutions, such as universities, often have their own IRBs that must approve all human subjects research before it is conducted within the institution. International Classification of Diseases (ICD) an official list of categories of diseases, physical and mental, issued by the World Health Organization (WHO). It is used primarily for statistical purposes in the classification of morbidity and mortality data. Any nation belonging to WHO may adjust the classification to meet specific needs (Mosby 2009).

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123 APPENDIX E Linkage analysis (LA) a gene-hunting technique that traces patterns of heredity in large, high-risk families in an attempt to locate a disease-causing gene muta - tion by identifying traits co-inherited with it; the formal study of the association between the inheritance of a condition in a family and a particular chromosomal locus; LA is based on certain ground rules of genetics (McGraw-Hill 2002). Lipidome the totality of lipids in cells (Quehenberger et al. 2010). Longitudinal study a research study that collects repeated observations of the same items over a long period of time (PCAST 2008). Metabolic profiling identifying the types and amounts of known metabolic intermediates present in a biological specimen. Metabolome can be defined as the complete complement of all small molecule (<1500 Da) metabolites found in a specific cell, organ, or organism. It is a close counterpart to the genome, the transcriptome, and the proteome. Together these four ‘omes’ constitute the building blocks of systems biology (Wishar et al. 2007). Microbiome term used to describe the collective genome of our indigenous mi- crobed (microflora) (Hooper and Gordon 2001 in IOM 2010b). Identification of the types of microbes present in a biological specimen or that are associated with another organism, such as a human. Molecular biology (A) a branch of biology dealing with the ultimate physico- chemical organization of living matter and especially with the molecular basis of inheritance and protein synthesis (Merriam-Webster 2007); (B) field of science concerned with the chemical structures and processes of biological phenomena at the molecular level (Merriam-Webster 2007). Moore’s Law the number of transistors that can be placed inexpensively on an integrated circuit doubles approximately every two years (Moore 1965). National Center for Biotechnology Information (NCBI) the National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information (NCBI 2011). Natural language processing a theoretically motivated range of computational techniques for analyzing and representing naturally occurring texts at one or more levels of linguistic analysis for the purpose of achieving human-like lan - guage processing for a range of tasks or applications (Liddy 2001) Observational studies although molecular data will be collected from indi- viduals in the normal course of health care, no changes in the treatment of the individuals would be contingent on the data collected.

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124 APPENDIX E Ontology a branch of metaphysics concerned with the nature and relations of being (Merriam-Webster 2007). Oophorectomy the surgical removal of an ovary (Merriam-Webster 2007). Outcomes research the systematic study of the effects of different therapeutic interventions on health outcomes. Pathogenesis the origination and development of a disease (Merriam-Webster 2007). Pathology (A) the study of the essential nature of diseases and especially of the structural and functional changes produced by them; (B) something abnormal: a : the structural and functional deviations from the normal that constitute disease or characterize a particular disease (Merriam-Webster 2007). Pathophysiology the physiology of abnormal states; specifically : the functional changes that accompany a particular syndrome or disease (Merriam-Webster 2007). Patient oriented research observation and scientific study of individuals or small groups of subjects for an understanding of their physiologic and patho - physiologic characteristics. The primary focus of the research is on mechanisms of disease on the clinical observations and laboratory studies that define these mechanisms as well as interventions that modify the course of the disease (APOR 2011). Personalized medicine (also see: Precision medicine) “refers to the tailoring of medical treatment to the individual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not” (PCAST 2008). This term is now widely used, including in advertisements for commercial products, and it is sometimes misinterpreted as implying that unique treatments can be designed for each individual. For this reason, the Committee thinks that the term “precision medicine” is preferable to “person - alized medicine” to convey the meaning intended in this report. Phenome-Wide Association Study (PheWAS) akin to the genome-wide as- sociation studies (GWAS) widely used today to find single nucleotide poly- morphisms (SNPs) that are genetically linked in a population to a particular disease trait—except that PheWAS is GWAS in reverse. GWAS associates geno- types with a given phenotype, such as height or a genetic disease. In contrast, PheWAS attempts to determine the range of clinical phenotypes associated with a given genotype (Mak 2011).

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125 APPENDIX E Phenotype the idiosyncratic traits exhibited by an organism, often categorized in terms of known trait variants. This can either refer to a specific trait or to a collection of traits. For example, blue eyes and brown eyes are phenotypes exhibited in subsets of humans. Phenotype-genotype association (or correlation) the association between the presence of a certain mutation or mutations (genotype) and the resulting physi - cal trait, abnormality, or pattern of abnormalities (phenotype). With respect to genetic testing, the frequency with which a certain phenotype is observed in the presence of a specific genotype determines the positive predictive value of the test (http://ghr.nlm.nih.gov/glossary=genotypephenotypecorrelation). Precision medicine (also see: Personalized Medicine) as used in this report, “precision medicine” refers to the tailoring of medical treatment to the indi - vidual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease, in the biology and/or prognosis of those diseases they may develop, or in their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing ex - pense and side effects for those who will not. Although the term “personalized medicine” is also used to convey this meaning, that term is sometimes misinter- preted as implying that unique treatments can be designed for each individual. For this reason, the Committee thinks that the term “precision medicine” is preferable to “personalized medicine” to convey the meaning intended in this report. It should be emphasized that in “precision medicine” the word “precision” is being used in a colloquial sense, to mean both “accurate” and “precise” (in the scientific method, the accuracy of a measurement system is the degree of closeness of measurements of a quantity to that quantity’s actual (true) value whereas the precision of a measurement system, also called repro- ducibility or repeatability, is the degree to which repeated measurements under unchanged conditions show the same results). http://en.wikipedia.org/wiki/ Accuracy_and_precision. the point where pharmacogenetics and personalised medicine meet (The Economist 2009). Precompetitive collaboration collaboration among competitors to achieve goals that can be more effectively accomplished by a group effort and have the po- tential to benefit everyone (IOM 2010a). Proteome the entire complement of proteins and associated modifications produced by an organism (PCAST 2008). Public–private partnerships agreement between a public agency (federal, state, or local) and a private sector entity. Through this agreement, the skills and

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126 APPENDIX E assets of each sector (public and private) are shared in delivering a service or facility for the use of the general public (NCPP 2011). Radioisotopic labeling the incorporation of radioactive atoms into DNA so that the DNA can be detected and visualized based on its emission of radioactivity. Recombinant DNA the artificial synthesis of sequences of DNA that may or may not exist in nature using genetic engineering techniques. These techniques are central to much of molecular biology and to the development of modern drugs. Sequelae a pathological condition resulting from a prior disease, injury, or at - tack (MedicineNet.com. 2011). Single Nucleotide Polymorphism (SNP) single genetic variation; DNA se- quence variations caused by single base changes at a given position in a genome. (PCAST 2008). Signs and symptoms objective evidence of disease perceptible to the examin- ing physician (sign) and subjective evidence of disease perceived by the patient (symptom). Social network an association of people drawn together by family, work, or hobby. Systematized Nomenclature of Medicine (SNOMED) a comprehensive clinical terminology, originally created by the College of American Pathologists (CAP) and, as of April 2007, owned, maintained, and distributed by the International Health Terminology Standards Development Organisation (IHTSDO), a not- for-profit association in Denmark. Systems analyses analysis of all aspects of a project along with ways to collect information about the operation of its parts (wordnetweb.princeton.edu/perl/ webwn). Transcriptome the complete set of RNA transcripts produced by the genome at any one time. The transcriptome is dynamic and changes under different circumstances due to different patterns of gene expression. The study of the transcriptome is termed transcriptomics (MedicineNet.com. 2011). Translational research transforms scientific discoveries arising from labora- tory, clinical, or population studies into clinical applications to reduce can - cer incidence, morbidity, and mortality. (NCI 2011). http://www.cancer.gov/ researchandfunding/trwg/TRWG-definition-and-TR-continuum. Whole-genome sequencing determining the sequence of deoxyribonucleotides that compose an entire genome, including all of its chromosomes.

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127 APPENDIX E GLOSSARY REFERENCES APOR (The Association for Patient Oriented Research). 2011 APOR http://www.apor.org/[ac - cessed October 10, 2011]. Economist. 2009. Getting Personal: The Promise of Cheap Genome Sequencing. The Econo - mist, April 16, 2009 [online]. Available: http://www.economist.com/node/13437974?story_ id=13437974 [accessed September 13, 2011]. ESRI (Environmental Systems Research Institute, Inc.). 1990. In Understanding GIS: The ARC/ INFO Method. Redlands, CA: ESRI, Pp. 1-2. Garets, D., and M. Davis. 2005. Electronic Patient Records: EMRs and EHRs. Healthcare Infor- matics [online]. Available: http://www.providersedge.com/ehdocs/ehr_articles/Electronic_ Patient_Records-EMRs_and_EHRs.pdf [accessed Aug. 25, 2011]. Hooper, L.V., and J.I. Gordon. 2001. Comensal host-bacterial relationships in the gut. Science 292(5519):1115-1118. Houghton Mifflin Company. 2007. The American Heritage Medical Dictionary. Boston, MA: Houghton Mifflin Company. InfoGlobalLink. 2011. Gene Expression Analysis [online]. Available: http://www.infogloballink. com/gene-sequencing/ [accessed September 13, 2011]. Information Buiders. 2011. Decision Support Systems-DSS [online]. Available: http://www. informationbuilders.com/decision-support-systems-dss [accessed Aug. 30, 2011]. IOM (Institute of Medicine). 2010a. Extending the Spectrum of Precompetitive Collaboration in Oncology Research: Workshop Summary. M. Patlack, S. Nass, E. Balogh, eds. Washington, DC: National Academies Press. IOM (Institute of Medicine). 2010b. Microbial Evolution and Co-Adaptation. Washington, DC: National Academies Press. Kahn, T.J., and H.S. Ninomiya, eds. 2010. Bioethics Thesaurus for Genetics. Washington, DC: Georgetown University [online]. Available: http://genethx.georgetown.edu/Bioethics ThesaurusForGeneticsSearchersGuide.pdf [accessed October 10, 2011]. Khoury, M.J. 2003. Genetics and genomics in practice: The continuum from genetic disease to genetic information in health and disease. Genet. Med. 5(4):261-268). Liddy, E.D. 2001. Natural language processing. In Encyclopedia of Library and Information Science, 2nd ed. New York: Marcel Decker [online]. Available: http://www.cnlp.org/ publications/03NLP.LIS.Encyclopedia.pdf [accessed October 10, 2011]. Mak, H.C. 2011. Discovery from data repositories. Nat. Biotechnol. 29:46-47. McGraw-Hill. 2002. Concise Dictionary of Modern Medicine. The McGraw-Hill Companies, Inc. Medical Dictionary. 2011. Medical Dictionary [online]. Available: http://de.dict.md/definition/ markers MedicineNet.com. 2011. Medical Dictionary [online]. Available: http://www.medterms.com/ script/main/hp.asp [accessed September 13, 2011]. Merriam-Webster. 2007.Merriam-Webster’s Dictionary [online]. Available: http://www.merriam- webster.com/browse/dictionary/a.htm?&t=1314709194 [accessed Aug. 30, 2011] Mizrachi, I. .2002. GenBank: The Nucleotide Sequence Database. Chapter 1 in the NCBI Handbook, J. McEntype, and J. Ostell, eds. Bethesda: National Center for Biotecnology Information. Moore, G. 1965. Cramming more components onto integrated circuits. Electronics 38(8) [online]. Available:ftp://download.intel.com/museum/Moores_Law/Articles-Press_Releases/Gordon_ Moore_1965_Article.pdf [accessed September 13, 2011]. Mosby. 2009. Mosby’s Medical Dictionary, 8th ed. Elsevier. NCBI (National Center for Biotechnology Information). 2011. dbGap: Database of Genotypes and Phenotypes. National Center for Biotechnology Information [online]. Available: http://www. ncbi.nlm.nih.gov/ [accessed Aug. 5, 2011].

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128 APPENDIX E NCI (National Cancer Institute). 2011. TRWG Definition of Translational Research [online]. Avail- able: http://www.cancer.gov/researchandfunding/trwg/TRWG-definition-and-TR-continuum [accessed September 13, 2011]. NCPP (National Council for Public-Private Partnership). 2011. How PPPs Work [online]. Avail - able: http://ncppp.org/howpart/index.shtml [accessed October 10, 2011]. NHGRI (National Human Genome Research Institute]. 2011. Talking Glossary of Genetics Terms [online]. Available: http://www.genome.gov/Glossary/index.cfm [accessed Aug. 25, 2011]. PCAST (President’s Council of Advisors on Science and Technology). 2008. Priorities for Per- sonalized Medicine. President’s Council of Advisors on Science and Technology, September 2008 [online]. Available: http://www.whitehouse.gov/files/documents/ostp/PCAST/pcast_ report_v2.pdf [accessed August 3, 2011]. Pigeot, I. 2005. Handbook of Epidemiology. Berlin: Springer, P. 95. Quehenberger, O., A.M. Armando, A.H. Brown, S.B. Milne, D.S. Myers, A.H. Merrill, S. Bandyopadhyay, K.N. Jones, S. Kelly, R.L. Shaner, C.M. Sullards, E. Wang, R.C. Murphy, R.M. Barkley, T.J. Leiker, C.R. H. Raetz, Z. Guan, G.M. Laird, D.A. Six, D.W. Russell, J.G. McDonald, S. Subramaniam, E. Fahy, and E.A. Dennis. 2010. Lipidomics reveals a remark- remark- able diversity of lipids in human plasma. J. Lipid Res. 51(11):3299-3305. Rappaport, S.M. 2011. Implications of the exposome for exposure science. J. Expo. Sci. Environ. Epidemiol. 21(1):5-9. Science Dictionary. 2011. Science Dictionary.com [online]. Available: http://www.science-diction - ary.com/definition/epigenome.html [accessed October 10, 2011]. USC (University of South California). 2011. Glossary. University of South California Norris Com - prehensive Cancer Center [online]. Available: http://uscnorriscancer.usc.edu/glossary/ [ac - cessed Aug. 25, 2011]. Wild, C.P. 2005. Complementing the genome with an “exposome”: The outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Bio - markers Prev. 14(8):1847-1850. Wishar, D.S, D. Tzur, C. Knox, R. Eisner, A.C. Guo, N. Young, D. Cheng, K. Jewell, D. Arndt, S. Sawhney, C. Fung, L. Nikolai, M. Lewis, M.A. Coutouly, I. Forsythe, P. Tang, S. Shrivastava, K. Jeroncic, P. Stothard, G. Amegbey, D. Block, D.D. Hau, J. Wagner, J. Miniaci, M. Clements, M. Gebremedhin, N. Guo, Y. Zhang, G.E. Duggan, G.D. Macinnis, A.M. Weljie, R. Dowlatabadi, F. Bamforth, D. Clive, R. Greiner, L. Li, T. Marrie, B.D. Sykes, H.J. Vogel, and L. Querengesser. 2007. HMDB: The Human Metabolome Database. Nucleic Acids Res. 35:D521-D526.