American Gastroenterological Association Future Trends Committee Report: The Application of Genomic and Proteomic Technologies to Digestive Disease Diagnosis and Treatment and Their Likely Impact on Gastroenterology Clinical Practice
2005; Elsevier BV; Volume: 129; Issue: 5 Linguagem: Inglês
10.1053/j.gastro.2005.06.047
ISSN1528-0012
AutoresKonstantinos N. Lazaridis, Brian D. Juran,
Tópico(s)Helicobacter pylori-related gastroenterology studies
ResumoThe American Gastroenterological Association (AGA) Future Trends Committee was created in 2004 to further the AGA Strategic Plan by identifying and characterizing important trends in clinical practice and scientific-technological developments in the world in general and medicine and gastroenterology in particular that potentially will impact the AGA and/or its members in the coming 3–5 years or beyond and to make strategic recommendations to the Governing Board on how AGA should deal with those trends and developments. These trends and developments may be economic, demographic, practice-based, scientific/technological or political in nature. Specifically, the committee is charged with preparing a report (or reports) for the AGA Governing Board that describes the trends or developments it has identified, postulates their impact on gastroenterology practice and/or research as appropriate, and presents specific recommendations for action by the AGA in terms of policy and programs. The committee is also asked to monitor these trends and technologies as they play out over time. In July 2004, the AGA Leadership Cabinet suggested several topics that the Future Trends Committee should address. Realizing that the Future Trends Committee could not realistically consider all of them, criteria were developed to prioritize the topics and others that might be added in the future. These criteria were as follows: •Time variable, that is, “when will gastroenterology be affected?”•Scale and magnitude•Does the trend or development represent a threat or opportunity (or both) to gastroenterology?•Effect on patient care quality and safety•Effect on AGA members and the AGA per se•Implications to reimbursement•Impact on gastroenterologists’ training and education. In October 2004, a crude Delphi process was used to determine the trends and developments that should be the focus of the committee’s work. Committee members were asked to assign priority scores to the items in the following list, which was based on the suggestions of the Leadership Cabinet and supplemented by AGA staff and others. This process was done via the mail. •The application of genomic and proteomic technologies to digestive disease diagnosis and treatment•Major changes in the US health care system and reimbursement•Increased median age of the population•Changes in the ethnic and racial makeup of the US population•Patients’ involvement in their own care•New colorectal cancer screening and diagnostic technologies•Biomedical research funding changes•Changes in academic health centers•Changes in physician education and training•Obesity-related disease incidence and prevalence•Computerization and digitization of gastroenterology practice Committee members were asked to score each item against each of the priority criteria noted previously using a scale in which 1 represents large effect and 3 represents small effect (on gastroenterology practice and research). The total scores of each topic were then summed and ranked. The 4 highest priority scores that resulted from this ranking were as follows: New colorectal cancer screening and diagnostic technologiesObesity-related diseaseAging of the populationGenomic and proteomic technologies. Because the AGA was already investigating the ramifications of the obesity epidemic, the Future Trends Committee decided to concentrate on the other 3 topics. The committee determined that preparing the 3 reports on its own was not feasible. Hence, it decided that it would solicit proposals from potential qualified authors to draft the reports and would modify and supplement the drafts as necessary. A request for proposal was prepared and disseminated in December 2004. The authors, who were paid for their work, were chosen by the committee from among the responses to the request for proposal. The manuscripts submitted by the authors were reviewed by the committee in February 2005. Among the changes to the draft reports were recommendations for action by the AGA; these were developed primarily by the committee. At its review meeting, the committee also developed a uniform format for the 3 reports. Revised manuscripts based on the committee’s critiques were completed in March 2005. The committee also had each report evaluated by an outside expert reviewer for completeness and to ensure that the authors had not made any egregious error that may have been overlooked. This report represents the committee’s recommendation for action by the AGA on this important topic. However, it is not the committee’s final word on the topic. Genomic and proteomic technologies will advance rapidly over the coming years, and the committee will revisit this subject periodically. Medicine is on the verge of an unprecedented prospect as a result of advances in the discipline of genomics and recent progress in the emerging field of proteomics. Human genomics is the study not just of single genes but also of the functions and interactions among all genes in the genome of humans. The significant evolution that has occurred in genomic science over the past 5 years holds promise to change our ability to better understand, diagnose, treat, and potentially prevent human illness. This unique opportunity stems from the completion of the Human Genome Project (HGP) and the development of novel technologies, several of which involve high-throughput automated assay systems (ie, genotyping platforms) and the application of bioinformation science (ie, bioinformatics). In a similar vein, the discipline of human proteomics is the study of the interactions among the various constituents of the entire proteome of humans. Human proteomics represents an extension of traditional biochemistry coupled with novel technologies (ie, tandem mass spectrometry) that seeks to take a more global approach to the assessment of the library of proteins specific to humans and understanding these proteomic relationships to health and disease. Because of the inevitable interconnection of the genome and proteome, genomics and proteomics should be viewed as complementary, rather than antagonizing, scientific fields. Nevertheless, the structure and function of the human proteome are far more complicated than those of the human genome. Simply stated, the genome (ie, genomic DNA) is a static, unwavering entity regarding its sequence and own duplication. In contrast, the proteome is a dynamic, ever-changing unit. For instance, the protein expression profiles in different human cells are highly variable, dependent on external or internal stimuli, not to mention the unique protein expression during the distinct stages of a person’s life cycle. In contrast, the genome of each human cell remains, in general, steady and unaltered over generations. To date, genomic science has mainly dissected the single-gene inherited diseases known as Mendelian disorders. Yet, the greatest promise and impact of genomic and proteomic research lie in their future application to complex or multifactorial diseases. In antithesis to Mendelian disorders, complex diseases arise due to the interplay of multiple genetic variants with environmental factors. Currently, the science and technology of human genomics greatly exceed the discipline of proteomics with respect to research discoveries and applications on science and influence on medical practice. The ultimate question addressed in this report is whether genomics, along with proteomics, will have an impact on future gastroenterology and hepatology clinical practice. Although we are unable to easily articulate a comprehensive answer to this vital and multifaceted question, we believe that genomics and proteomics hold vast potential and almost certainly will shape the way we diagnose and treat patients with digestive and hepatic disorders in years to come. For eons, humans have understood that heredity, along with the environment, shape our phenotypic diversity and contribute to disease. Yet, it was not until 2003 that the entire sequence of the human genome was elucidated via the HGP, providing the biologic basis for a better understanding of heredity and likely the interaction of environment on the genetic material. To date, the enormity of information regarding our own blueprint of life awaits meticulous investigation, the overall aim of which is to identify the genetic components of disease susceptibility, thus improving diagnosis, therapy, and disease prevention. To this extent, well-designed translational studies in gastrointestinal (GI) and liver diseases are urgently needed to transform such colossal genomic knowledge into a meaningful outcome that can be incorporated into clinical practice and benefit the sick. Since the early 1990s, we have made momentous progress in unraveling the genes causing digestive and hepatic Mendelian diseases such as familial adenomatous polyposis (FAP), hereditary hemochromatosis, and hereditary pancreatitis, to name a few. Although the prevalence of such diseases is low, the understanding of the relevant genetic defects has unquestionably shed light on the biology of the GI system and liver. In the genome era, however, the tools are becoming available to begin dissecting common complex diseases such as irritable bowel syndrome (IBS), nonalcoholic fatty liver disease, inflammatory bowel disease (IBD), and many others. Recognizing the unparalleled genetic and environmental intricacy of those complex diseases, we have to realize that greater challenges lie ahead. In this scientific struggle, technological innovations will be a strong ally. Newly available genotyping platforms now compete to provide greater data quality at higher throughput. Importantly, federally funded initiatives are currently in place to develop state-of-the-art whole genome sequencing technologies at relatively affordable cost. Dr. Harold Varmus, Nobel Laureate and former director of the National Institutes of Health, wrote in a 2002 editorial in the New England Journal of Medicine that, “the publication last year of nearly complete sequences of the human genome, did not mean that the practice of medicine would be abruptly and radically transformed… Still, changes in medical practice are already occurring at an accelerating pace under the influence of the elucidation of genomes.”1Varmus H. Getting ready for gene-based medicine.N Engl J Med. 2002; 347: 1526-1527Crossref PubMed Scopus (64) Google Scholar The clinical impact of genomic and proteomic technologies in gastroenterology and hepatology will become profound as we better define the environmental influence and genetic predilection to related complex diseases. This is simply because of the high prevalence of complex diseases in the population. From a pragmatic view, we predict that the existing disparity between gathering information on the inherited human material and its application toward preventing, diagnosing, and treating complex GI and liver diseases will close in the coming decades. To achieve such progress, however, we need first to develop high-quality translational clinical studies and to test hypotheses pertinent to the pathogenesis and therapy of the diseases of interest. This endeavor will require the coordinated effort of applying the knowledge and technologies of genomics, proteomics, and related disciplines. The ultimate goal is to dissect the genetic variants that function not as direct causes of but as predisposing factors to development of digestive and hepatic illnesses. In closing, we bear in mind that the proposed transformation toward genomic medicine is not solely dependent on scientific discovery. What has to be clearly understood and acted on is the concern that the assumed impact of genomics and proteomics in clinical practice will not be attained without educating gastroenterology trainees, gastroenterologists and hepatologists, health care professionals, and our patients not only about the clinical applications but also the limitations and threats of using genetic information in medical practice. To this end, confidentiality and equality of genetic information, accuracy of genetic testing, prevention of genetic discrimination, and the psychological impact of knowing the genetic susceptibility to disease will continue to confront healthcare providers, patients and their relatives, and society alike. About 50 years ago, when James Watson and Francis Crick reported the discovery of the double helical structure of DNA, perhaps hardly any gastroenterologist paid attention to their article in the journal Nature.2Watson J.D. Crick F.H. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid.Nature. 1953; 171: 737-738Crossref PubMed Scopus (4007) Google Scholar Since then, this seminal finding has transformed the biologic sciences. In the past 2 decades, this scientific breakthrough provided the cornerstone of an international scientific collaboration known as the HGP, which aimed at sequencing the complete genome of Homo sapiens.3Lander E.S. Linton L.M. Birren B. Nusbaum C. Zody M.C. Baldwin J. Devon K. Dewar K. Doyle M. FitzHugh W. Funke R. Gage D. Harris K. Heaford A. Howland J. Kann L. Lehoczky J. LeVine R. McEwan P. McKernan K. Meldrim J. Mesirov J.P. Miranda C. Morris W. Naylor J. Raymond C. Rosetti M. Santos R. Sheridan A. Sougnez C. Stange-Thomann N. Stojanovic N. Subramanian A. Wyman D. Rogers J. Sulston J. Ainscough R. Beck S. Bentley D. Burton J. Clee C. Carter N. Coulson A. Deadman R. Deloukas P. Dunham A. Dunham I. Durbin R. French L. Grafham D. Gregory S. Hubbard T. Humphray S. Hunt A. Jones M. Lloyd C. McMurray A. Matthews L. Mercer S. Milne S. Mullikin J.C. Mungall A. Plumb R. Ross M. Shownkeen R. Sims S. Waterston R.H. Wilson R.K. Hillier L.W. McPherson J.D. Marra M.A. Mardis E.R. Fulton L.A. Chinwalla A.T. Pepin K.H. Gish W.R. Chissoe S.L. Wendl M.C. Delehaunty K.D. Miner T.L. Delehaunty A. Kramer J.B. Cook L.L. Fulton R.S. Johnson D.L. Minx P.J. Clifton S.W. Hawkins T. Branscomb E. Predki P. Richardson P. Wenning S. Slezak T. Doggett N. Cheng J.F. Olsen A. Lucas S. Elkin C. Uberbacher E. Frazier M. Gibbs R.A. Muzny D.M. Scherer S.E. Bouck J.B. Sodergren E.J. Worley K.C. Rives C.M. Gorrell J.H. Metzker M.L. Naylor S.L. Kucherlapati R.S. Nelson D.L. Weinstock G.M. Sakaki Y. Fujiyama A. Hattori M. Yada T. Toyoda A. Itoh T. Kawagoe C. Watanabe H. Totoki Y. Taylor T. Weissenbach J. Heilig R. Saurin W. Artiguenave F. Brottier P. Bruls T. Pelletier E. Robert C. Wincker P. Smith D.R. Doucette-Stamm L. Rubenfield M. Weinstock K. Lee H.M. Dubois J. Rosenthal A. Platzer M. Nyakatura G. Taudien S. Rump A. Yang H. Yu J. Wang J. Huang G. Gu J. Hood L. Rowen L. Madan A. Qin S. Davis R.W. Federspiel N.A. Abola A.P. Proctor M.J. Myers R.M. Schmutz J. Dickson M. Grimwood J. Cox D.R. Olson M.V. Kaul R. Raymond C. Shimizu N. Kawasaki K. Minoshima S. Evans G.A. Athanasiou M. Schultz R. Roe B.A. Chen F. Pan H. Ramser J. Lehrach H. Reinhardt R. McCombie W.R. de la Bastide M. Dedhia N. Blocker H. Hornischer K. Nordsiek G. Agarwala R. Aravind L. Bailey J.A. Bateman A. Batzoglou S. Birney E. Bork P. Brown D.G. Burge C.B. Cerutti L. Chen H.C. Church D. Clamp M. Copley R.R. Doerks T. Eddy S.R. Eichler E.E. Furey T.S. Galagan J. Gilbert J.G. Harmon C. Hayashizaki Y. Haussler D. Hermjakob H. Hokamp K. Jang W. Johnson L.S. Jones T.A. Kasif S. Kaspryzk A. Kennedy S. Kent W.J. Kitts P. Koonin E.V. Korf I. Kulp D. Lancet D. Lowe T.M. McLysaght A. Mikkelsen T. Moran J.V. Mulder N. Pollara V.J. Ponting C.P. Schuler G. Schultz J. Slater G. Smit A.F. Stupka E. Szustakowski J. Thierry-Mieg D. Thierry-Mieg J. Wagner L. Wallis J. Wheeler R. Williams A. Wolf Y.I. Wolfe K.H. Yang S.P. Yeh R.F. Collins F. Guyer M.S. Peterson J. Felsenfeld A. Wetterstrand K.A. Patrinos A. Morgan M.J. de Jong P. Catanese J.J. Osoegawa K. Shizuya H. Choi S. Chen Y.J. International Human Genome Sequencing ConsortiumInitial sequencing and analysis of the human genome.Nature. 2001; 409: 860-921Crossref PubMed Scopus (11719) Google Scholar, 4Venter J.C. Adams M.D. Myers E.W. Li P.W. Mural R.J. Sutton G.G. Smith H.O. Yandell M. Evans C.A. Holt R.A. Gocayne J.D. Amanatides P. Ballew R.M. Huson D.H. Wortman J.R. Zhang Q. Kodira C.D. Zheng X.H. Chen L. Skupski M. Subramanian G. Thomas P.D. Zhang J. Gabor Miklos G.L. Nelson C. Broder S. Clark A.G. Nadeau J. McKusick V.A. Zinder N. Levine A.J. Roberts R.J. Simon M. Slayman C. Hunkapiller M. Bolanos R. Delcher A. Dew I. Fasulo D. Flanigan M. Florea L. Halpern A. Hannenhalli S. Kravitz S. Levy S. Mobarry C. Reinert K. Remington K. Abu-Threideh J. Beasley E. Biddick K. Bonazzi V. Brandon R. Cargill M. Chandramouliswaran I. Charlab R. Chaturvedi K. Deng Z. Di Francesco V. Dunn P. Eilbeck K. Evangelista C. Gabrielian A.E. Gan W. Ge W. Gong F. Gu Z. Guan P. Heiman T.J. Higgins M.E. Ji R.R. Ke Z. Ketchum K.A. Lai Z. Lei Y. Li Z. Li J. Liang Y. Lin X. Lu F. Merkulov G.V. Milshina N. Moore H.M. Naik A.K. Narayan V.A. Neelam B. Nusskern D. Rusch D.B. Salzberg S. Shao W. Shue B. Sun J. Wang Z. Wang A. Wang X. Wang J. Wei M. Wides R. Xiao C. Yan C. Yao A. Ye J. Zhan M. Zhang W. Zhang H. Zhao Q. Zheng L. Zhong F. Zhong W. Zhu S. Zhao S. Gilbert D. Baumhueter S. Spier G. Carter C. Cravchik A. Woodage T. Ali F. An H. Awe A. Baldwin D. Baden H. Barnstead M. Barrow I. Beeson K. Busam D. Carver A. Center A. Cheng M.L. Curry L. Danaher S. Davenport L. Desilets R. Dietz S. Dodson K. Doup L. Ferriera S. Garg N. Gluecksmann A. Hart B. Haynes J. Haynes C. Heiner C. Hladun S. Hostin D. Houck J. Howland T. Ibegwam C. Johnson J. Kalush F. Kline L. Koduru S. Love A. Mann F. May D. McCawley S. McIntosh T. McMullen I. Moy M. Moy L. Murphy B. Nelson K. Pfannkoch C. Pratts E. Puri V. Qureshi H. Reardon M. Rodriguez R. Rogers Y.H. Romblad D. Ruhfel B. Scott R. Sitter C. Smallwood M. Stewart E. Strong R. Suh E. Thomas R. Tint N.N. Tse S. Vech C. Wang G. Wetter J. Williams S. Williams M. Windsor S. Winn-Deen E. Wolfe K. Zaveri J. Zaveri K. Abril J.F. Guigo R. Campbell M.J. Sjolander K.V. Karlak B. Kejariwal A. Mi H. Lazareva B. Hatton T. Narechania A. Diemer K. Muruganujan A. Guo N. Sato S. Bafna V. Istrail S. Lippert R. Schwartz R. Walenz B. Yooseph S. Allen D. Basu A. Baxendale J. Blick L. Caminha M. Carnes-Stine J. Caulk P. Chiang Y.H. Coyne M. Dahlke C. Mays A. Dombroski M. Donnelly M. Ely D. Esparham S. Fosler C. Gire H. Glanowski S. Glasser K. Glodek A. Gorokhov M. Graham K. Gropman B. Harris M. Heil J. Henderson S. Hoover J. Jennings D. Jordan C. Jordan J. Kasha J. Kagan L. Kraft C. Levitsky A. Lewis M. Liu X. Lopez J. Ma D. Majoros W. McDaniel J. Murphy S. Newman M. Nguyen T. Nguyen N. Nodell M. Pan S. Peck J. Peterson M. Rowe W. Sanders R. Scott J. Simpson M. Smith T. Sprague A. Stockwell T. Turner R. Venter E. Wang M. Wen M. Wu D. Wu M. Xia A. Zandieh A. Zhu X. The sequence of the human genome.Science. 2001; 291: 1304-1351Crossref PubMed Scopus (7614) Google Scholar This large-scale biologic endeavor occurred over 13 years (1990–2003).3Lander E.S. Linton L.M. Birren B. Nusbaum C. Zody M.C. Baldwin J. Devon K. Dewar K. Doyle M. FitzHugh W. Funke R. Gage D. Harris K. Heaford A. Howland J. Kann L. Lehoczky J. LeVine R. McEwan P. McKernan K. Meldrim J. Mesirov J.P. Miranda C. Morris W. Naylor J. Raymond C. Rosetti M. Santos R. Sheridan A. Sougnez C. Stange-Thomann N. Stojanovic N. Subramanian A. Wyman D. Rogers J. Sulston J. Ainscough R. Beck S. Bentley D. Burton J. Clee C. Carter N. Coulson A. Deadman R. Deloukas P. Dunham A. Dunham I. Durbin R. French L. Grafham D. Gregory S. Hubbard T. Humphray S. Hunt A. Jones M. Lloyd C. McMurray A. Matthews L. Mercer S. Milne S. Mullikin J.C. Mungall A. Plumb R. Ross M. Shownkeen R. Sims S. Waterston R.H. Wilson R.K. Hillier L.W. McPherson J.D. Marra M.A. Mardis E.R. Fulton L.A. Chinwalla A.T. Pepin K.H. Gish W.R. Chissoe S.L. Wendl M.C. Delehaunty K.D. Miner T.L. Delehaunty A. Kramer J.B. Cook L.L. Fulton R.S. Johnson D.L. Minx P.J. Clifton S.W. Hawkins T. Branscomb E. Predki P. Richardson P. Wenning S. Slezak T. Doggett N. Cheng J.F. Olsen A. Lucas S. Elkin C. Uberbacher E. Frazier M. Gibbs R.A. Muzny D.M. Scherer S.E. Bouck J.B. Sodergren E.J. Worley K.C. Rives C.M. Gorrell J.H. Metzker M.L. Naylor S.L. Kucherlapati R.S. Nelson D.L. Weinstock G.M. Sakaki Y. Fujiyama A. Hattori M. Yada T. Toyoda A. Itoh T. Kawagoe C. Watanabe H. Totoki Y. Taylor T. Weissenbach J. Heilig R. Saurin W. Artiguenave F. Brottier P. Bruls T. Pelletier E. Robert C. Wincker P. Smith D.R. Doucette-Stamm L. Rubenfield M. Weinstock K. Lee H.M. Dubois J. Rosenthal A. Platzer M. Nyakatura G. Taudien S. Rump A. Yang H. Yu J. Wang J. Huang G. Gu J. Hood L. Rowen L. Madan A. Qin S. Davis R.W. Federspiel N.A. Abola A.P. Proctor M.J. Myers R.M. Schmutz J. Dickson M. Grimwood J. Cox D.R. Olson M.V. Kaul R. Raymond C. Shimizu N. Kawasaki K. Minoshima S. Evans G.A. Athanasiou M. Schultz R. Roe B.A. Chen F. Pan H. Ramser J. Lehrach H. Reinhardt R. McCombie W.R. de la Bastide M. Dedhia N. Blocker H. Hornischer K. Nordsiek G. Agarwala R. Aravind L. Bailey J.A. Bateman A. Batzoglou S. Birney E. Bork P. Brown D.G. Burge C.B. Cerutti L. Chen H.C. Church D. Clamp M. Copley R.R. Doerks T. Eddy S.R. Eichler E.E. Furey T.S. Galagan J. Gilbert J.G. Harmon C. Hayashizaki Y. Haussler D. Hermjakob H. Hokamp K. Jang W. Johnson L.S. Jones T.A. Kasif S. Kaspryzk A. Kennedy S. Kent W.J. Kitts P. Koonin E.V. Korf I. Kulp D. Lancet D. Lowe T.M. McLysaght A. Mikkelsen T. Moran J.V. Mulder N. Pollara V.J. Ponting C.P. Schuler G. Schultz J. Slater G. Smit A.F. Stupka E. Szustakowski J. Thierry-Mieg D. Thierry-Mieg J. Wagner L. Wallis J. Wheeler R. Williams A. Wolf Y.I. Wolfe K.H. Yang S.P. Yeh R.F. Collins F. Guyer M.S. Peterson J. Felsenfeld A. Wetterstrand K.A. Patrinos A. Morgan M.J. de Jong P. Catanese J.J. Osoegawa K. Shizuya H. Choi S. Chen Y.J. International Human Genome Sequencing ConsortiumInitial sequencing and analysis of the human genome.Nature. 2001; 409: 860-921Crossref PubMed Scopus (11719) Google Scholar, 4Venter J.C. Adams M.D. Myers E.W. Li P.W. Mural R.J. Sutton G.G. Smith H.O. Yandell M. Evans C.A. Holt R.A. Gocayne J.D. Amanatides P. Ballew R.M. Huson D.H. Wortman J.R. Zhang Q. Kodira C.D. Zheng X.H. Chen L. Skupski M. Subramanian G. Thomas P.D. Zhang J. Gabor Miklos G.L. Nelson C. Broder S. Clark A.G. Nadeau J. McKusick V.A. Zinder N. Levine A.J. Roberts R.J. Simon M. Slayman C. Hunkapiller M. Bolanos R. Delcher A. Dew I. Fasulo D. Flanigan M. Florea L. Halpern A. Hannenhalli S. Kravitz S. Levy S. Mobarry C. Reinert K. Remington K. Abu-Threideh J. Beasley E. Biddick K. Bonazzi V. Brandon R. Cargill M. Chandramouliswaran I. Charlab R. Chaturvedi K. Deng Z. Di Francesco V. Dunn P. Eilbeck K. Evangelista C. Gabrielian A.E. Gan W. Ge W. Gong F. Gu Z. Guan P. Heiman T.J. Higgins M.E. Ji R.R. Ke Z. Ketchum K.A. Lai Z. Lei Y. Li Z. Li J. Liang Y. Lin X. Lu F. Merkulov G.V. Milshina N. Moore H.M. Naik A.K. Narayan V.A. Neelam B. Nusskern D. Rusch D.B. Salzberg S. Shao W. Shue B. Sun J. Wang Z. Wang A. Wang X. Wang J. Wei M. Wides R. Xiao C. Yan C. Yao A. Ye J. Zhan M. Zhang W. Zhang H. Zhao Q. Zheng L. Zhong F. Zhong W. Zhu S. Zhao S. Gilbert D. Baumhueter S. Spier G. Carter C. Cravchik A. Woodage T. Ali F. An H. Awe A. Baldwin D. Baden H. Barnstead M. Barrow I. Beeson K. Busam D. Carver A. Center A. Cheng M.L. Curry L. Danaher S. Davenport L. Desilets R. Dietz S. Dodson K. Doup L. Ferriera S. Garg N. Gluecksmann A. Hart B. Haynes J. Haynes C. Heiner C. Hladun S. Hostin D. Houck J. Howland T. Ibegwam C. Johnson J. Kalush F. Kline L. Koduru S. Love A. Mann F. May D. McCawley S. McIntosh T. McMullen I. Moy M. Moy L. Murphy B. Nelson K. Pfannkoch C. Pratts E. Puri V. Qureshi H. Reardon M. Rodriguez R. Rogers Y.H. Romblad D. Ruhfel B. Scott R. Sitter C. Smallwood M. Stewart E. Strong R. Suh E. Thomas R. Tint N.N. Tse S. Vech C. Wang G. Wetter J. Williams S. Williams M. Windsor S. Winn-Deen E. Wolfe K. Zaveri J. Zaveri K. Abril J.F. Guigo R. Campbell M.J. Sjolander K.V. Karlak B. Kejariwal A. Mi H. Lazareva B. Hatton T. Narechania A. Diemer K. Muruganujan A. Guo N. Sato S. Bafna V. Istrail S. Lippert R. Schwartz R. Walenz B. Yooseph S. Allen D. Basu A. Baxendale J. Blick L. Caminha M. Carnes-Stine J. Caulk P. Chiang Y.H. Coyne M. Dahlke C. Mays A. Dombroski M. Donnelly M. Ely D. Esparham S. Fosler C. Gire H. Glanowski S. Glasser K. Glodek A. Gorokhov M. Graham K. Gropman B. Harris M. Heil J. Henderson S. Hoover J. Jennings D. Jordan C. Jordan J. Kasha J. Kagan L. Kraft C. Levitsky A. Lewis M. Liu X. Lopez J. Ma D. Majoros W. McDaniel J. Murphy S. Newman M. Nguyen T. Nguyen N. Nodell M. Pan S. Peck J. Peterson M. Rowe W. Sanders R. Scott J. Simpson M. Smith T. Sprague A. Stockwell T. Turner R. Venter E. Wang M. Wen M. Wu D. Wu M. Xia A. Zandieh A. Zhu X. The sequence of the human genome.Science. 2001; 291: 1304-1351Crossref PubMed Scopus (7614) Google Scholar If the “pregenomic era” was concluded by the complete sequencing of the 3.2 billion nucleotides of the human genome in 2003, we have already entered the “genome era.”5Guttmacher A.E. Collins F.S. Welcome to the genomic era.N Engl J Med. 2003; 349: 996-998Crossref PubMed Scopus (149) Google Scholar As stated provocatively by Francis Collins, Director of the National Human Genome Research Institute (NHGRI), “all disease—aside from most cases of trauma—have a genetic component.”6Collins F.S. The human genome project and the future of medicine.Ann N Y Acad Sci. 1999; 882 (discussion 56–65): 42-55Crossref PubMed Scopus (33) Google Scholar Genetic and environmental contributions have been proposed in several GI and liver diseases for more than a century. To date, we have observed published work on the genetic contributions in colon cancer, hereditary hemochromatosis, IBD, and IBS, to mention a few. This trend will only continue to increase in the genome era, with implications for practicing or experimental gastroenterologists and hepatologists alike, regardless of our intellectual prejudicial approaches to understand the pathogenesis of, diagnose, treat, and prevent digestive and hepatic disorders. To successfully treat illness, it is imperative to first understand how a disease state is caused. Unraveling the pathogenesis of a disorder provides a means to intersect with disease processes and hopefully to alter the natural history of an illness toward cure or prevention. As we know it, there are 2 elements, whose interaction leads to many human diseases. The first is the inevitable environmental exposures/risks to which we are constantly exposed, even before birth. The second is the genetic predisposition we have inherited from our parents. These 2 components have to be dissected to shed light on disease pathogenesis if we wish to improve our current diagnostic methods and treatments. To evaluate the environmental component of an illness is challenging. To assess the genetic inclination to disease is a daunting but attainable goal, because the genetic material is generally considered steady and today can be tested in the laboratory. To this end, the genetic information derived from completion of the HGP will facilitate such efforts by thrusting forward the discipline of genomics and aiding the emergence of the field of proteomics. These 2 interrelated scientific subjects and other associated disciplines such as genetic epidemiology and bioinformatics will definitely advance basic studies and translational clinical investigations to elucidate the genetic predilection and environmental factors causing disease. Recognizing the need to exemplify the mission of the above scientific fields, a few definitions are offered. Human genomics is a scientific field that examines the structure, function, and interaction of all the genes and genetic elements in the human genome.7Guttmacher A.E. Collins F.S. Genomic medicine—a primer.N Engl J Med. 2002; 347: 1512-1520Crossref PubMed Scopus (369) Google Scholar Human proteomics is an emerging discipline that aspires to study the human proteome in health and disease using a variety of methodologies.8Posadas E.M. Simpkins F. Liotta L.A. MacDonald C. Kohn E.C. Proteomic analysis for the early detection and rational treatment of cancer—realistic hope?.Ann Oncol. 2005; 16: 16-22Crossref PubMed Scopus (81) Google Scholar Genetic epidemiology is the study of the role of genetic factors and their interaction with environmental elements in the occurrence of disease in human populations.9Kaprio J. Science, medicine, and the future genetic epidemiology.BMJ. 2000; 320: 1257-1259Crossref PubMed Google Scholar Bioinformatics is the use of computer science and methods for the purpose of speeding up and enhancing biologic research.10Altman R.B. Bioinformatics in support of molecular medicine.Proc AMIA Symp. 1998; : 53-61PubMed Google Scholar Amid the current exhilarating scientific progress, we pose 2 questions. (1) Will genomics and proteomics have an impact on the manner that we will use to diagnose and treat GI and liver disorders in the future? (2) If so, when will this transformation occur? A short answer to the first question is “almost positively,” but a reply to the second query is not easy. Most likely this revolution will steadily ensue in the forthcoming decades, although variations in lead-time are anticipated among different digestive and hepatic diseases. In the following pages of this report, an effort is made to assess the application of genomic and proteomic technologies to the diagnosis and treatment of GI and liver diseases and their proposed impact on the clinical practice of physicians who treat such patients. Our given task is challenging. To this extent, we would like to make 3 statements concerning the structure and scope of this report. First, the genomic era and the related scientific fields of human genomics and proteomics are currently at their developmental stage. A plethora of genomic data have been generated and analyzed as a result
Referência(s)