You can't always sequence your way out of a tight spot

Abstract

Diagnostic tests for microbial pathogens have been used in clinical practice long before DNA sequencing technologies were developed. Many of us have personal experience with throat swabs to diagnose strep throat caused by the bacterium Streptococcus pyogenes or nose swabs to diagnose flu caused by the influenza virus. Public health officials are also interested in reliable diagnostic tests to protect us from emerging epidemics such as the recent Ebola and Zika outbreaks, or from food‐borne illnesses that all too frequently make the headlines. Doctors, public health officials, biodefense experts, and many others critically rely on pathogen detection and characterization technologies to diagnose, prevent, treat, and investigate infectious disease.Are DNA sequencing technologies fast and accurate enough to transform the field of pathogen diagnostics?Many of the existing tests rely on culturing on media that is known to enrich the targeted pathogen. Incubation times for a positive diagnosis can be as short as 1 or 2 days, but may require up to 5 days for many pathogens, and even weeks in certain cases, such as Nocardia and Actinomyces spp. High‐throughput DNA sequencing technologies have enormous potential to change this state of affairs. The hope is that these technologies will enable culture‐free pathogen diagnostic approaches that are fast, sensitive, and have broad diagnostic capabilities. One can easily imagine a situation where a doctor would place a sample into a microfluidic device that extracts its DNA and feeds it into a rapid sequencing device. The resulting data would be analyzed computationally to determine the identity of the pathogen or pathogens contained in the sample, to propose a strain‐specific treatment regime, and to provide the full sequence of the pathogen(s) for further analysis. The entire process could take just a few hours or perhaps minutes.There is no doubt that DNA sequencing technologies have already transformed …