JAMA: Genomics Topic Collection

Metagenomics, Infectious Disease Diagnostics, and Outbreak Investigations Sequence First, Ask Questions Later? Metagenomics and Infectious Disease Diagnostics

Relman DA. — Wed, 10 Apr 2013 00:00:00 GMT

Revolutionary advances in DNA sequencing technology are radically changing the approach for studying and characterizing the microbial world. The sequencing of a microbial genome, which can now be achieved in preliminary form in hours, provides a wealth of information about the functional potential of the organism, its evolutionary relationships with other organisms, and clues about niche adaptation, and without the need for microbial cultivation or isolation. Likewise, so-called shotgun or metagenomic sequencing, which is the high-throughput simultaneous sequencing of random fragments from complex mixes of different genomes, provides insights into the potential activities of a microbial community, possible interactions between microbial community members, and the nature of their relationships with their environment (eg, a human host).

Genomics in Medicine Maturation, but Not Maturity Genomics in Medicine

Feero W. — Wed, 10 Apr 2013 00:00:00 GMT

April 14, 2013, marks the 10-year anniversary of the official completion of the entire Human Genome Project. This genomics theme issue celebrates recent remarkable advances made possible by one of the greatest biological research projects ever conducted. During the last decade, understanding the complexity of the genome has moved beyond infancy into early childhood, a precarious age of exploration filled with an increasing number of triumphs and the occasional mishap. For the field of genomics, this developmental period has been marked by rapid advances in technologies for dissecting genome function in health and disease. Perhaps most surprisingly, the cost of sequencing the genome has decreased by 5 orders of magnitude through roughly the last 10 years, a pace that has exceeded expectations. Many types of basic and clinical studies that would have been unthinkably expensive a decade ago are now quite achievable and proceeding quickly. Reflected in the 2011 strategic vision document authored by the National Human Genome Research Institute is an increasing and welcome trend toward rationally exploring how genomic discoveries affect health.

Human Genome Initiatives Make Strides to Better Understand Health and Disease

Hampton T. — Wed, 10 Apr 2013 00:00:00 GMT

Ten years after the completion of the Human Genome Project, scientists continue to use information on the sequence and location of human genes to better understand wellness and disease. Some of the progress made so far was highlighted at a recent meeting of the National Advisory Council for Human Genome Research, which meets 3 times a year to advise federal agencies in the United States on genetics, genomic research, training, and programs related to the human genome initiative.

A Culture-Independent Sequence-Based Metagenomics Approach to the Investigation of an Outbreak of Shiga-Toxigenic Escherichia coli O104:H4 Outbreak of Shiga-toxigenic Escherichia coli

Loman NJ, Constantinidou C, Christner M, et al. — Wed, 10 Apr 2013 00:00:00 GMT

Importance

Identification of the bacterium responsible for an outbreak can aid in disease management. However, traditional culture-based diagnosis can be difficult, particularly if no specific diagnostic test is available for an outbreak strain.

Objective

To explore the potential of metagenomics, which is the direct sequencing of DNA extracted from microbiologically complex samples, as an open-ended clinical discovery platform capable of identifying and characterizing bacterial strains from an outbreak without laboratory culture.

Design, Setting, and Patients

In a retrospective investigation, 45 samples were selected from fecal specimens obtained from patients with diarrhea during the 2011 outbreak of Shiga-toxigenic Escherichia coli (STEC) O104:H4 in Germany. Samples were subjected to high-throughput sequencing (August-September 2012), followed by a 3-phase analysis (November 2012-February 2013). In phase 1, a de novo assembly approach was developed to obtain a draft genome of the outbreak strain. In phase 2, the depth of coverage of the outbreak strain genome was determined in each sample. In phase 3, sequences from each sample were compared with sequences from known bacteria to identify pathogens other than the outbreak strain.

Main Outcomes and Measures

The recovery of genome sequence data for the purposes of identification and characterization of the outbreak strain and other pathogens from fecal samples.

Results

During phase 1, a draft genome of the STEC outbreak strain was obtained. During phase 2, the outbreak strain genome was recovered from 10 samples at greater than 10-fold coverage and from 26 samples at greater than 1-fold coverage. Sequences from the Shiga-toxin genes were detected in 27 of 40 STEC-positive samples (67%). In phase 3, sequences from Clostridium difficile, Campylobacter jejuni, Campylobacter concisus, and Salmonella enterica were recovered.

Conclusions and Relevance

These results suggest the potential of metagenomics as a culture-independent approach for the identification of bacterial pathogens during an outbreak of diarrheal disease. Challenges include improving diagnostic sensitivity, speeding up and simplifying workflows, and reducing costs.

Genomic Medicine

Goodman DM, Lynm C, Livingston EH. — Wed, 10 Apr 2013 00:00:00 GMT

Genomic medicine, sometimes also known as personalized medicine, is a way to customize medical care to your body's unique genetic makeup. Each of the cells in the body contains DNA, the molecules you inherit from your parents that determine how your body looks and functions. DNA is arranged like a twisted ladder, with information stored in the arrangement, or sequence, of the rungs. Sections of the DNA ladder that contain information needed to make proteins are known as genes. The entire structure is the genome. A nearly complete map of the DNA sequence was completed in 2003, and since then, scientists have worked to understand how each gene functions and how it is coordinated with every other gene. The human genome may contain 20 000 to 23 000 genes.

Genomic Medicine, Health Information Technology, and Patient Care Genomic Medicine and Health Information Technology

Chute CG, Kohane IS. — Wed, 10 Apr 2013 00:00:00 GMT

Celebrating the tenth anniversary of completing the draft human genome sequence in 2011, authors from the National Human Genome Research Institute of the US National Institutes of Health outlined the influence of genomic understanding across 5 domains: structure, the biology of the genome, the biology of disease, medicine, and improvements in health care. The authors assert that this is the era of enhanced genomic understanding of medicine, which is expected to usher in improvements in health care effectiveness by the end of this decade. It is thus fitting to explore how health information technology will contribute to or hamper the promise of genomic medicine.

The Indispensable Role of Professional Judgment in Genomic Medicine Professional Judgment in Genomic Medicine

McGuire AL, McCullough LB, Evans JP. — Wed, 10 Apr 2013 00:00:00 GMT

Whole-genome sequencing and whole-exome sequencing (WGS/WES) have become increasingly affordable and accessible to individuals. There are currently 3 main pathways through which a person can receive WGS/WES: as a research participant in a genomic study; through a direct-to-consumer personal genome company; or as part of clinical care. In the research context, the extent to which findings from WGS/WES are communicated to study participants and used to inform their clinical care is a topic of much debate, but guidelines suggest that investigators may have an obligation to offer at least some results to study participants.

Realizing the Opportunities of Genomics in Health Care The Opportunities of Genomics in Health Care

Ginsburg GS. — Wed, 10 Apr 2013 00:00:00 GMT

April 14, 2013, marks the 10th anniversary of the completion of the Human Genome Project. Concurrently, the nation is in the process of reforming health care, with the aims of reducing costs, increasing access, and improving outcomes. One decade since the Human Genome Project's end, the question remains, how has sequencing the human genome contributed to achieving these goals? When addressing this question it is important to remember that the Human Genome Project was not conceived with health care reform–related goals in mind. Rather it was an audacious scientific challenge that took advantage of the preeminence of the United States in life sciences to advance and accelerate knowledge of the fundamental biology of humans, as is necessary for the progress of medicine.

Accessing Genomic Medicine Affordability, Diffusion, and Disparities Accessing Genomic Medicine

Tuckson RV, Newcomer L, De Sa JM. — Wed, 10 Apr 2013 00:00:00 GMT

Advances in the understanding of the genome, combined with affordable sequencing techniques and innovations in drug development, are ushering in an era of molecular diagnostics and individualized therapeutics with the potential to meaningfully enhance human health through effective prevention, diagnosis, and treatment. As the genetic origins of many diseases become better understood, risks and prognoses can be assessed based upon knowledge of genetic mutations, while biomarkers are becoming available to predict pharmacologic response in unique patients. This revolution in genomic medicine, sometimes also called personalized or precision medicine, has the ability to advance both disease prevention and patient outcomes.