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UMB Team to Use $410K NIAID Grant to Build Microbial Detection Pipeline for NGS-based Dx

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Researchers from the University of Maryland, Baltimore, are using a $410,000 grant from the National Institutes of Health to build an informatics infrastructure that can support whole-genome sequencing-based microbial diagnostics in clinical settings.

The system consists of a database of reference bacterial sequences and an analysis pipeline based on the Cloud Virtual Resource, or CloVR, a virtual research platform developed by the UMB team that comprises pre-configured, automated pipelines for analyzing microbial genomes (BI 10/28/2011).

The two-year project, which began last year, is funded by the National Institute of Allergy and Infectious Diseases and is intended to demonstrate "the feasibility of building an automated diagnostic pipeline to support genome sequence analysis for microbial isolate typing, virulence, and antimicrobial resistance profiling, and phylogenetic classification," according to its abstract.

"There have been very interesting proof-of-concept papers on applications of whole genome sequencing for clinical microbiology," Florian Fricke, an assistant professor of microbiology and immunology at UMB and one of the principal investigators on the grant, told BioInform. "The goal of our project is to build on those studies … but then try to bridge the gap and solve the problems that need to be solved in order to … get into the clinic."

Although it's based on CloVR, Fricke told BioInform that the diagnostic version of the pipeline will be much simpler to use than its research counterpart with much of the underlying functionality hidden from clinicians. Clinicians will be able to compare their raw sequence data to the reference datasets to determine which bacterial strains are present in the specimen sample and by extension which course of treatment to adopt.

The researchers plan to make the supporting reference database open to the community so that others can add in new reference sequences. For now, it contains sequences of bacteria from the Enterobacteriaceae family, such as Salmonella, Escherichia coli, and Shigella, but it could be extended to include sequences from other kinds of bacteria such as Staphylococcus aureus and Campylobacter.

Also, since CloVR runs on the cloud, smaller hospitals wouldn’t have to invest in additional infrastructure in order to use the tool, he said.

If this phase of the project succeeds, the UMB researchers intend to apply for more funding to run a second three-year validation project during which they'll test the pipeline on clinical samples provided by collaborators at the University of Maryland Medical Center, also in Baltimore, and the US Food and Drug Administration.

As part of that process, "we will select, implement, and test the sequencing platform [that] is most affordable and applicable to the field setting with respect to cost, space, effort, and data generation, as well as training for setup and operation," the current grant abstract states.

Fricke hasn’t decided which sequencer to use with the pipeline. "It's safe to say [that] it's probably going to be the Ion torrent PGM or the Illumina MiSeq" but "it's too early to make that call," he said. For now, CloVR supports both platforms, he said.

Also according to the current grant, in the next phase, the researchers plan to pit the "utility and accuracy" of using whole-genome sequencing against traditional methods of characterizing bacterial isolates current used in clinics.

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