In order to prioritize our development of a molecular multi-disease detection strategy for the infectious diseases in children, Dr. Versalovic has created a 10-year plan for Texas Children’s Diagnostic Testing Research Project.
An in-depth look at the 10-Year plan
The focus for the first half of the 10-year plan is to design and optimize the strategies for next generation sequencing with the intention of generating data that will translate into new diagnostic advancements. By the end of this plan, we will have refined the diagnostic multi- disease molecular detection technology through the utilization of sequencing and will have started using the new diagnostic tools to help pediatric patients. Each generation of molecular diagnostics will be faster and more expansive, holding an updated library of identifiable microbes made possible by the discovery phase. During this discovery period, scientists will work with actual patient cases and scenarios at Texas Children’s Hospital to help determine the groups of bacteria or viruses that should be targeted first due to gaps in currently available tests. Collaboration with other researchers such as Susan Lynch, Ph.D., at University of California, San Francisco and Gregory Storch, M.D., at Washington University in St. Louis School of Medicine will aid in the procurement of samples and protocols necessary for optimization of the application of these new technologies. The project also will be submitted to the institutional review board at Baylor College of Medicine for approval as a human studies protocol. This approval will allow the researchers to use current and archived pediatric patient samples to facilitate the discovery and development phases of the project.
In addition to our work on the diagnostic component of the multi-disease detection strategy, we anticipate that our researchers could help identify new infectious organisms and disease-causing agents. Sequences generated from the project also will be used to develop or customize testing based on the symptoms displayed by a particular patient. For example, sequencing tests could be tailored to diseases of the central nervous system, respiratory infections or gastrointestinal problems. As viruses and disease-causing bacteria evolve, or new ones are discovered, their DNA would be added to the expanding library of knowledge used for the development of new sequencing strategies.
require “known” pathogens for probe design. With well optimized sequencing protocols, new pathogen discovery as well as rare pathogen identification would be possible from a single patient sample. Metagenomics, the study of a microbial community without the need for pure culture, is a rapidly advancing field, and the research team is poised with the necessary experience and environment to become leaders in the use of metagenomics for diagnostic development. As highlighted by initial virome (the genome of viruses) studies, it is key to develop technologies where it is possible to detect what you know you’re looking for but still find what you didn’t know you were looking for. Well-designed large-scale next generation sequencing is the obvious path towards this goal.
Once the most important groups of bacteria and viruses have been determined and initial trials have been completed using several sequencing strategies, expanded development targeting multiple pathogens will take place. The selected technologies will be used to develop the first generation multi-disease molecular diagnostic tests for clinical evaluation at Texas Children’s Hospital. As platforms and technologies improve, additional groups of important pediatric viruses and bacteria will be added to the tests. This continuous expansion of the tests, both by increased potential of the technology and new discoveries in the first phase of the project, will ensure that the project keeps moving forward to potentially make the greatest impact possible.
The various technologies to be explored for the project will all rely on the sequences obtained during the discovery phase. All work done using a specific testing platform or technology (for example, a certain piece of equipment or reagent) will be easily transitioned to development on additional diagnostic options. No work will be lost by performing trials on various instruments or trials of multiple technologies. Ultimately, the best strategy for pediatric care will be employed for clinical implementation in the diagnosis phase of the project.
The incorporation of other advanced technologies such as the Luminex bead technology, a liquid bead array with a capacity of 100 sequence targets in a single sample, and the newly launched RainDance Technologies, a droplet-based polymerase chain reaction (PCR) approach that exponentially increases the number of sequence targets that can be handled at one time, will play an important role in the development of the sequencing strategies for diagnostic use. The ability to maintain a core group of scientific personnel who are well-versed in all of these cutting edge technologies is a huge asset to this project team, and development plans will continue to be modified as new products and technologies are introduced to the molecular diagnostics market.