DNA sequencing on the spot saved the life of a 14-year-old boy who had meningoencephalitis (a swollen brain due to infection) for 4 months. Since the medical team could not determine a diagnosis based on brain biopsies and blood tests, they resorted to next-generation sequencing of DNA to successfully determine the cause of the brain infection.
A report of this case was published in the New England Journal of Medicine this month. The team that took care of the boy and determined the cause of the infection were from the University of California in San Francisco.
Next-generation sequencing of DNA is a new, fast technique for determining the sequence of the nucleotides (specifically ATCGs) that make up a strand of DNA. A genome is the total sequence information of all the DNA in an individual. Also, the genome of a given species can be described as the complete DNA sequence that makes up all the chromosomes in that species.
In the case of this 14-year-old boy, since they could not find the source of his infection using conventional methods, they decided to use a method that is not normally used for clinical diagnosis. Next-generation sequencing of DNA has only been routinely used for research studies.
When they used next-generation DNA sequencing on the spot to save the boy’s life, they took a sample of cerebrospinal fluid from his body and found the DNA sequence of whatever was present in the fluid. This was called unbiased sequencing. The results from sequencing the DNA in the cerebrospinal fluid identified many section of DNA sequences that were matched to a microbe called leptospira. This result meant that leptospira was the culprit in the brain infection.
An important part of this type of analysis is to be able to match the results from the next-generation DNA sequencing to already known sequences from an organism. The scientific community has been working very hard over the last two decades to determine the DNA sequences of many microbes, plants, animals, and even humans. A new field, called bioinformatics, has been created to be able to process the massive amount of DNA sequence information that has resulted from all this work. In the case of the 14-year-old boy, they initially found the sequences of three million fragments of DNA. The bioinformatics analysis was able to sort through all that data in a short period of time.
Once they determined that leptospira was the cause of the infection, they knew what medication to give to the boy and he subsequently recovered. The boy likely contracted this bacteria during a trip to Puerto Rico.
The use of DNA sequencing on the spot to save lives is not something that will likely be widely used in the clinic soon. However, there is great potential that this kind of technology could be useful in many diseases that are hard to diagnosis currently. Diagnosing Lyme disease has been suggested as a possibility in the future. Instead of running tests for specific suspected pathogens, next-generation DNA sequencing could be used to sort of “shotgun” a search for the disease-causing pathogen.
By Margaret Lutze