A new algorithm designed by researchers at McMaster University in Canada can help detect harmful pathogens, such as SARS-CoV-2, quickly and in highly mixed samples.
The tool allows researchers to design targeted probes that are able to detect even very small amounts of pathogens in environmental samples, such as wastewater, a process that can otherwise be problematic.
“A wide array of metagenomic research efforts are hampered by the same challenge: low concentrations of targets of interest combined with overwhelming amounts of background signal,” write Zachery Dickson, a graduate student in the Department of Biology at McMaster, and colleagues in the journal Cell Reports: Methods.
“Although PCR or naive DNA capture can be used when there are a small number of organisms of interest, design challenges become untenable for large numbers of targets.”
For this reason, the research team set out to build an algorithm that could help design more accurate probes and help avoid the need to bulk sequence samples – a long and costly process.
The HUBDesign pipeline, available on GitHub, uses sequence homology to design probes at many taxonomic levels. The developers tested the algorithm by designing probes for all 56 known coronaviruses, including SARS-CoV-2, and also for a range of sepsis causing bacteria such as Streptococcus species.
For the coronavirus probes, it took the team less than a day for design. The genomes were sorted into representative species within an hour and candidate species were identified in less than a minute and using less than 1GB of computer power.
“However, processing 56 viral genomes is a minor task compared with the capabilities of the pipeline,” write the authors, who say that while memory requirements scale linearly with genome size and number of organisms, adding significant numbers of species can increase the time requirement of the process considerably.
They also tested the capacity of the probe design for 1926 sepsis pathogens across 81 species. “There are thousands of bacterial pathogens and being able to determine which one is present in a patient’s blood sample could lead to the correct treatment faster when time is very important,” explained Dickson, first author of the paper, in a press statement.
“The probe makes identification much faster, meaning we could potentially save people who might otherwise die.”
The researchers plan to continue improving the HUBDesign pipeline and testing it for other uses. One example of this includes identifying intestinal parasites in ancient DNA samples, something that lead author and evolutionary geneticist Hendrik Poinar, director of McMaster’s Ancient DNA Centre, is keen to explore.
“We currently need faster, cheaper and more succinct ways to detect pathogens in human and environmental samples that democratize the hunt and this pipeline does exactly that,” he says.