More Use of Whole Gene Sequencing Poised to Play Important New Roles in Microbiology and Medical Laboratory Testing

DARK Daily Laboratory and Pathology News (http://www.darkdaily.com/) recently predicted that gene sequencing is on a fast track to move from research settings into clinical laboratories, as rapid gene sequencing and whole genome sequencing technologies are giving microbiologists new tools to quickly identify microbes and other infectious disease agents.

In clinical laboratories across the nation, microbiology has greatly benefited from the introduction of molecular diagnostics in clinical practice. Now the field of microbiology is poised to undergo a more profound transformation of clinical practice, due to advances in whole genome sequencing.

Leaders in this field are calling these developments “transformative” and say they have the potential to change “all aspects of microbiology.” The driver to this emerging trend is advanced technology that makes it possible to sequence the whole gene sequence of an organism in a day or less, for a cost that is $1,000 and falling rapidly.

In the past six months, microbiologists and pathologists at such hospitals as Methodist Hospital in Houston, Texas, have begun to do whole genome sequencing of microbes found in specimens collected from patients arriving in the emergency room. The New York Times wrote about these developments in a story titled “The New Generation of Microbe Hunters,” that it published on August 29, 2011.

Medical Laboratories May Soon Be Gene Sequencing Microbes

Medical laboratory managers may be surprised to learn how swiftly this specialized area of microbiology is advancing. In a paper published in the New England Journal of Medicine (NEJM) last summer, David A. Relman, M.D., Professor, Medicine-Infectious Diseases, Microbiology, Immunology, provided information about progress in whole genome sequencing of infectious disease agents.

He provided a list of the current state of microbial genomics. Some of that data follows:

- 1,554 complete bacterial genome sequences (representing mostly pathogens) have been published, with 4,800 more in progress.

- 112 complete archaeal genome sequences have been determined and 90 more are in progress.

- 41 complete eukaryotic genome sequences have been determined (19 from fungi), plus another 1,100 are in progress.

- 2,765 viral species have complete reference genome sequences available.

Relman had several predictions which can be used by clinical laboratory administrators and pathologists to anticipate developments in the field of clinical microbiology. In the NEJM story, Relman wrote that, “Genome sequencing of a microbe or virus will soon be easier than characterization of its growth-based behavior in the laboratory. In the next three to five years, direct shotgun sequencing of the DNA and RNA in a clinical sample may become a routine matter.”

Relman went on to write that, “The power of full-genome sequencing to discriminate between closely related strains and track real-time evolution of disease-associated clonal isolates offers the possibility of tracing person-to-person transmission and identifying point sources of outbreaks.”

This is a role that clinical laboratories can perform. In fact, Relman gave an example of this type of clinical diagnostic application. He stated that, “Using this approach, investigators established a previously unrecognized link among five patients with the same clonal strain of methicillin-resistant Staphylococcus aureus from a hospital in Thailand.”

Many pathologists recall recent events in Haiti. After a half century without a case of cholera in Haiti, in the months following the 2010 earthquake, there was a major cholera outbreak. Gene sequencing of the cholera strain was used to determine that the source of the outbreak was nearly identical to strains circulating in South Asia. Eventually, that cholera outbreak was traced back to United Nations peacekeepers from Nepal. Contamination by fecal matter from their camp infected local water sources. Since then, approximately 520,000 cholera cases have been reported in Haiti, along with about 7,000 deaths attributed to the disease.

Cheaper, Faster, More Accurate Gene Sequencing Can Change Microbiology

These are examples that show how cheaper, faster, and more accurate gene sequencing technologies are poised to transform clinical microbiology. That’s the opinion of Matthew K. Waldor, M.D., Ph.D., of Harvard Medical School. In The New York Times story, he stated that this new technology “is changing all aspects of microbiology. It’s just transformative.”

It was Waldor, in a collaboration with James M. Musser, M.D., Ph.D., Chairman of Pathology and Genomic Medicine at the Methodist Hospital System, who used rapid gene sequencing to investigate the source of the cholera outbreak in Haiti.

Another one of Drs. Waldor and Musser’s contemporaries is Eric Schadt, Ph.D., Chairman of Genetics at Mount Sinai School of Medicine in New York City, and the Chief Scientific Officer at Pacific Biosciences. Schadt is engrossed with making disease “weather maps.” Developed from swabs and samples from public venues such as surfaces in subways and hospitals, as well as from fecal samples in sewage treatment plants, disease weather maps would provide real-time tracking of what bacteria and viruses are present in a particular area and how prevalent they are.

Through genetic testing of sewage, for example, Schadt was able to determine what disease-causing microbes were present from a particular population. “This is like public health epidemiology,” Schadt told The New York Times. “We could start assessing the dietary composition of a region and correlate it with health.”

Collectively, the examples provided in this Dark Daily e-briefing show how quickly microbiologists, infectious disease doctors, and pathologists are applying rapid gene sequencing and whole gene sequencing to a wide range of research and clinical purposes. Pathologists and clinical laboratory executives will recognize that, at this stage in the technology development of these tools, it is not a matter of when, but how fast they will find a place in microbiology and clinical laboratory testing.