Continuation of application No. 1 1/546,827, filed on Oct. 11, 2006, now Pat. No. 7,292,057, which is a continuation of application No. 10/626,903, filed on Jul. 25, 2003, now Pat. No. 7,138,813, which is a continuation of application No. 10/308,847, filed on Dec. 2, 2002, now Pat. No. 6,642,732, which is a continuation of application No. 10/179,771, filed on Jun. 24, 2002, now Pat. No. 6,512,391, which is a continuation of application No. 09/345,571, filed on Jun. 30, 1999, now Pat. No. 6,445,202. (63)

There is an urgent need for effective genomics education for healthcare professionals. Recent analysis of an experimental genomics curriculum showed that medical students' examinations of their own genotypes provide a valuable learning experience. Such experiential learning has a long tradition in medical education and its application to genomics is enabled by increasingly powerful and decreasingly costly genome science and technology. Personal genotyping is an important option to consider when designing educational programs for healthcare professionals.

Personalized MedicineVol. 9, No. 3 EditorialFree AccessPathologists and the third wave of medical genomicsMark S BoguskiMark S BoguskiCenter for Biomedical Informatics, Harvard Medical School & Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Published Online:4 May 2012https://doi.org/10.2217/pme.12.27AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: diagnostic servicesgenetic polymorphismsgenomicshealthcare reformlaboratory accreditationlaboratory medicinemultifactorial diseasespersonalized medicinepharmaceutical industrypresymptomatic genotypingvalidated drug targetsOver the past two decades, our notions about how genome science and technology would improve health and healthcare have changed. The first wave of medical genomics occurred in the mid-to-late 1990s during the pioneer period of the Human Genome Project and led to overly optimistic expectations about the development of abundant new drugs [1,2]. This optimism rested on rapid and massive gene discovery that would, in turn, quickly yield hundreds if not thousands of new and novel drug 'targets', whose roles in disease would be rapidly 'validated' through new technologies, especially comparative [3], functional [4] and structural [5] genomics. A plethora of new drugs designed to antagonize these targets and thereby effectively treat or cure disease would then ensue. In reality, only a handful of genome-derived drugs have reached the market to date.The second wave of medical genomics arose from a flood of genome-wide association studies that linked common genetic polymorphisms with the risks of developing complex (multifactorial) human diseases such as hypertension and Type 2 diabetes [6] and the year 2007 was called an annus mirabilis of the genome era in medicine [7]. The wake of this second wave led to a number of direct-to-consumer, quasi-medical services that promised customers a 'health compass' to manage their risks of disease [8]. The impact of these services has been more educational [9] and recreational than medical [10]. Despite optimistic projections about the impact of the first two waves of genomic medicine, progress in improving human health has been modest and incremental rather than paradigm shifting.The first two waves of medical genomics focused on therapeutics and presymptomatic testing for disease risk assessment. The third wave of genomic medicine, namely postsymptomatic genotyping for individualized and optimized disease management, is likely to bring the most direct and sustained impact on healthcare for several reasons [11]. Insofar as genomics technologies enable disease diagnosis of sufficient precision to drive both cost-effective management and better patient outcomes, they are an essential part of the prescription for disruptive healthcare reform [12].The first two waves of medical genomics were largely within the purviews of the pharmaceutical industry and primary care and public health communities. The third wave, triggered by sharp declines in the cost of next-generation DNA sequencing technologies [13], falls clearly within the realm of laboratory medicine and pathology. Pathologist-directed, licensed clinical laboratory testing has a major effect on clinical decision-making; despite the fact that laboratory services account for only about 2.3% of healthcare expenditures in the USA, these services strongly influence the remaining 98% of costs through the information they provide on the prevention, diagnosis, treatment and management of disease [101].Pathologists are physician custodians of laboratory testing and the diagnostic enablers of clinical medicine. The analysis of bodily fluids and tissue specimens for disease diagnoses and monitoring responses to therapy is what pathologists do every day; genome analytics are just another technology in the evolution of molecular diagnostics [11]. Genome analytics have now reached a stage of maturity that demands assessment of their routine clinical application [14]. Workforce training and preparation is well underway and already a core component of a growing number of residency training programs [15,16]. In addition to their daily role in healthcare delivery, pathologists, via their professional organizations, play essential roles in federally mandated [17] certification, accreditation and proficiency testing of clinical laboratories [18].The third wave of medical genomics, characterized by collaboration between pathologists and other members of comprehensive healthcare delivery teams, may finally help us realize the benefits that genome science and technology have long promised.Financial & competing interests disclosureMS Boguski is a consultant for GNS Healthcare, a scientific advisor to GenomeQuest, Inc., and a cofounder of Genome Health Solutions, Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.References1 Drews J. Genomic sciences and the medicine of tomorrow. Nat. Biotechnol.14(11),1516–1518 (1996).Crossref, Medline, CAS, Google Scholar2 Hopkins AL, Groom CR. The druggable genome. Nat. Rev. Drug Dis.1(9),727–730 (2002).Crossref, Medline, CAS, Google Scholar3 Bassett DE Jr, Boguski MS, Spencer F et al. Genome cross-referencing and XREFdb: implications for the identification and analysis of genes mutated in human disease. Nat. Genet.15(4),339–344 (1997).Crossref, Medline, CAS, Google Scholar4 Hieter P, Boguski M. Functional genomics: it's all how you read it. Science278(5338),601–602 (1997).Crossref, Medline, CAS, Google Scholar5 Shapiro L, Lima CD. The argonne structural genomics workshop: lamaze class for the birth of a new science. Structure6(3),265–267 (1998).Crossref, Medline, CAS, Google Scholar6 Burton PR, Clayton DG, Cardon LR, et al.; Wellcome Trust Case Control Consortium.Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature477(7145),661–678 (2007).Crossref, Google Scholar7 Davies K. The $1,000 genome: the revolution in DNA sequencing and the new era of personalized medicine. Free Press, NY, USA (2010).Google Scholar8 Davies K. Keeping score of your sequence. Bio-IT World, 12 November (2008).Google Scholar9 Haspel RL, Arnaout R, Briere L et al. A Curriculum in genomics and personalized medicine for pathology residents. Am. J. Clin. Path.133(Online Suppl.),1–3 (2010).Crossref, Google Scholar10 Bloss CS, Madlensky L, Schork NJ, Topol EJ. Genomic information as a behavioral health intervention: can it work? Per. Med.8(6),659–667 (2011).Link, Google Scholar11 Boguski MS, Arnaout R, Hill C. Customized care 2020: how medical sequencing and network biology will enable personalized medicine. F1000 Biol. Rep.1,73 (2009).Crossref, Medline, Google Scholar12 Christensen CM, Grossman JH, Hwang J. The innovator's prescription: a disruptive solution for health care. McGraw-Hill, NY, USA (2009).Google Scholar13 Mardis ER. A decade's perspective on DNA sequencing technology. Nature470(7333),198–203 (2011).Crossref, Medline, CAS, Google Scholar14 Kuehn BG. NIH shifts focus from sequencing genes to fostering clinical applications. JAMA307(2),132 (2012).Crossref, Medline, CAS, Google Scholar15 Haspel RL, Arnaout R, Briere L et al. A call to action: training pathology residents in genomics and personalized medicine. Am. J. Clin. Pathol.133(6),832–834 (2010).Crossref, Medline, Google Scholar16 Tonellato PJ, Crawford JM, Boguski MS, Saffitz JE. A national agenda for the future of pathology in personalized medicine: report of the proceedings of a meeting at the banbury conference center on genome-era pathology, precision diagnostics, and preemptive care: a stakeholder summit. Am. J. Clin. Pathol.135(5),668–672 (2011).Crossref, Medline, Google Scholar17 Centers for Medicare & Medicaid Services; US Department of Health and Human Services. Medicare, Medicaid and CLIA programs; continuance of the approval of the College of American Pathologists as a CLIA accreditation organization. Federal Register66(177),47493–47497 (2001).Google Scholar18 Rabinovitch A. The college of American pathologists laboratory accreditation program. Accreditation and quality assurance. J. Qual. Comparability Reliability Chem. Measurement7(11),473–476 (2002).Google Scholar101 Wolcott J, Schwartz A, Goodman C; The Lewin Group. Laboratory medicine: a national status report (2008). www.futurelabmedicine.org/pdfs/2007%20status%20report%20laboratory_medicine_-_a_national_status_report_from_the_lewin_group_updated_2008-9.pdfGoogle ScholarFiguresReferencesRelatedDetailsCited ByIdentification of Molecular Alterations Challenging Initial Pathologic Classification in Cases of Clinician-Initiated Next-Generation Sequencing Testing23 June 2021 | American Journal of Clinical Pathology, Vol. 156, No. 6Personal genotypes are teachable momentsGenome Medicine, Vol. 5, No. 3 Vol. 9, No. 3 Follow us on social media for the latest updates Metrics History Published online 4 May 2012 Published in print May 2012 Information© Future Medicine LtdKeywordsdiagnostic servicesgenetic polymorphismsgenomicshealthcare reformlaboratory accreditationlaboratory medicinemultifactorial diseasespersonalized medicinepharmaceutical industrypresymptomatic genotypingvalidated drug targetsFinancial & competing interests disclosureMS Boguski is a consultant for GNS Healthcare, a scientific advisor to GenomeQuest, Inc., and a cofounder of Genome Health Solutions, Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download

In its report Healthy People 2020, the U.S. Department of Health and Human Services states that one of its major objectives is to use communication strategically to improve health and that one of the ways in which this can be done is through images of health in the media and popular culture. Health information campaigns have traditionally relied on mass communication (such as public service announcements on billboards, radio and television) and educational messages in printed materials. However, fueled by social networking technologies and the emergence of participatory medicine, the ways in which consumers find and use health information are undergoing dramatic change. Based on new insights into the theory and operational characteristics of “teachable moments”, and novel adaptations of theoretical models of health behavior change, we have created a multi-channel platform to systematically create and distribute Teachable Moments in Medicine® using blogs, Facebook and Twitter. This system has the potential to educate and inform millions of consumers in a cost-effective manner since three-fourths of all Americans are online and virtually all take some interest in popular culture. The system has also proven popular among professional healthcare providers as a new mode of communication and understanding with their patients. []

In October 2010, representatives and thought leaders from major national pathology organizations and a diverse group of other stakeholders gathered at the Banbury Conference Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, to examine opportunities and challenges facing the discipline of pathology and its future role in the rapidly developing field of personalized medicine. A major focus of the meeting was assessment of the potential impact of next-generation sequencing (NGS) and whole-genome analysis (WGA) in medicine and, specifically, in clinical laboratory practice. (We define WGA as the sequencing of DNA and the alignment, variation calling, quality estimation, and annotation of one entire human genome.) The clearly articulated goal of the pathologists in attendance was to develop a national strategy to ensure that the performance, interpretation, and regulation of genome-based clinical testing come directly under the purview of pathologists and their national organizations. In devising a strategy to guide the development of “genome era” pathology, 3 fundamental themes emerged from the discussions: 1. A lifetime of genomic information. NGS is a “disruptive” technology capable of catalyzing fundamental changes in medical care. It is increasingly plausible to anticipate that healthy people, including newborns, will have their genomes sequenced as the foundation of personalized programs of lifelong health promotion, disease prevention, and, when necessary, disease management. This paradigm shift in clinical laboratory testing presents the discipline of pathology with an unprecedented opportunity to reinvent itself as a primary care discipline . At the least, pathologists have the opportunity to provide expert support to every physician—primary care or otherwise—who cares for people whose genomic information is known. There is also an opportunity for pathologists to be curators of genomic information during the course of each person’s lifetime, providing up-to-date interpretations of genomic information in the context of intercurrent health events and needs. 2. Pathology scope …

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.

Genomics and "medical sequencing" will revolutionize clinical laboratory diagnostics as the foundation for the new era of personalized medicine. However, the medical profession lags far behind the technology and business communities in recognizing and preparing for this change. Pathologists must take the lead in the application of genomics technologies, including whole-genome sequencing, to laboratory diagnostics and personalized medicine. As a critical first step in leading this change, we have established a first-in-the-nation resident curriculum in genomics and personalized medicine. Our goal is to catalyze the adoption of similar training modules in every pathology residency in North America. If we succeed in the widespread implementation of this type of training as a core competency in pathology, we will ensure that the discipline of pathology will lead rather than follow in the coming era of personalized medicine.

Genetic Testing and Molecular BiomarkersVol. 14, No. 6 RoundtableTrust It or Trash It? A Tool for Evaluating the Quality of Genetic InformationJoseph D. McInerney, Mark S. Boguski, Pat Furlong, and Benjamin HeywoodJoseph D. McInerneyNational Coalition for Health Professional Education in Genetics, Lutherville, Maryland.Search for more papers by this author, Mark S. BoguskiCenter for Biomedical Informatics, Harvard Medical School, and Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.Search for more papers by this author, Pat FurlongParent Project Muscular Dystrophy (PPMD), Middletown, Ohio and Fort Lee, New Jersey.Search for more papers by this author, and Benjamin HeywoodPatientsLikeMe, Inc., Cambridge, Massachusetts.Search for more papers by this authorPublished Online:15 Dec 2010https://doi.org/10.1089/gtmb.2010.1512AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byWho writes this stuff? Musculoskeletal information quality and authorship of popular health websites: A systematic reviewMusculoskeletal Science and Practice, Vol. 60 Volume 14Issue 6Dec 2010 InformationCopyright 2010, Mary Ann Liebert, Inc.To cite this article:Joseph D. McInerney, Mark S. Boguski, Pat Furlong, and Benjamin Heywood.Trust It or Trash It? A Tool for Evaluating the Quality of Genetic Information.Genetic Testing and Molecular Biomarkers.Dec 2010.743-748.http://doi.org/10.1089/gtmb.2010.1512Published in Volume: 14 Issue 6: December 15, 2010Online Ahead of Print:September 20, 2010PDF download

Consumer activism, genetic information, and social networking technologies are creating many opportunities for drug repurposing.

Applications of next-generation nucleic acid sequencing technologies will lead to the development of precision diagnostics that will, in turn, be a major technology enabler of precision medicine. Terabyte-scale, multidimensional data sets derived using these technologies will be used to reverse engineer the specific disease networks that underlie individual patients’ conditions. Modeling and simulation of these networks in the presence of virtual drugs, and combinations of drugs, will identify the most efficacious therapy for precision medicine and customized care. In coming years the practice of medicine will routinely employ network biology analytics supported by high-performance supercomputing.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of ∼20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.