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Pathogenetix Targets 2012 Launch for 'Sequence Shorthand' Tech to ID Microbes


by Monica Heger

Pathogenetix is planning a late 2012 launch for its genome-scanning platform for microbial identification, which is expected to cost between $125,000 and $150,000 per instrument with reagent costs ranging in the tens of dollars per sample.

The Woburn, Mass.-based company, which changed its name from US Genomics last year, recently closed an $11 million Series B financing round that will take it through commercialization, David Hooey, Pathogenetix's vice president of business development, told In Sequence.

The company's technology is designed to identify individual microbial strains from a heterogeneous sample. Hooey said the system will have applications initially in research and later in pathogen testing for food, water, and environmental samples and ultimately in clinical diagnostics of infectious diseases.

The technology, which Hooey described as "sequence shorthand," is similar in principle to systems from OpGen and BioNano Genomics that provide information about genome architecture without sequencing. Pathogenetix is solely focused on microbial identification, however, which sets it apart from these firms, he said.

When a heterogeneous sample is loaded into the Pathogenetix platform, a single reagent set first distinguishes microbial DNA from host DNA by degrading the cell material while keeping all the microbial genomes intact — whether there is just one strain or multiple strains.

Next, restriction enzymes cut the DNA into fragments between 60 kilobase pairs and 350 kilobase pairs and fluorescent probes are inserted into the DNA, staining the length of the backbone. Then, the system adds eight-base-long sequence-specific probes — one red and one green — that are used to identify the strains.

The prepared DNA is then loaded into a microfluidic chip, stretched out, and shot past a detector at 150 million base pairs per second, which identifies the strain based on the spatial pattern of red and green tags. Run time for a sample is around three and a half hours.

Pathogenetix has a database on microbial genomes that currently comprises 1,500 sequenced microbes in the public domain and another 500 from private collections. The company uses its platform to determine the spatial pattern for each microbe and loads that into its database. Each organism yields between five and 20 DNA fragments with unique patterns.

As samples are run through the detector, the company's software identifies strains based on the number of hits against the database. If all fragments match, the strain is an exact match. If some match, then the sample is of the same species, but not the exact strain.

The company updates its database every few weeks, adding more microbe sequences, and expects that it will increase it by several fold as it nears product launch. Additionally, researchers will be able to load sequences from their own collections to the database.

Hooey said one near-term application will be in microbial research and piecing together family trees of bacterial species. For instance, in a sample with multiple strains of Staphylococcus aureus, the system can determine how the strains are related, allowing researchers to study different resistance profiles or understand why some populations respond differently to antibiotics.

While the system will not provide whole-genome sequence data, Hooey said it could be used to prioritize sequencing.

The technology provides a "molecular fingerprint" that can be used to "profile a collection of microbes" or "give an inventory of what we're seeing in a particular sample," he said. Additionally, the technology allows researchers to "track changes in a time course."

Aside from pure research, the technology will also have applications in monitoring food, beverages, or pharmaceuticals for contamination, Hooey said. Unlike PCR-based assays, which test for specific contaminants, Pathogenetix's probes are unspecific, so will identify any microbe or pathogen contamination. Additionally, he added, because it yields detailed information about the strain, it can track the outbreak and potentially identify the origin of the pathogen.

Ultimately, the goal is to move the technology into clinical diagnostics of infectious diseases, Hooey said. The system could be used at the point of care to identify a pathogen from a stool sample, for instance. "You don't have to say, 'I think it's staph, let me get the staph test,'" he said, because the reagent sets are nonspecific, and will churn out an answer in just a few hours for between $25 and $50 per sample.

He predicted that once the platform is available for research use, likely at the end of 2012, it will be another six months before it enters the clinic.

The company has developed functional prototypes that it is using internally and is working on forming partnerships in the three key applications it is targeting: microbial research, environmental monitoring, and clinical diagnostics. Some of those partnerships will likely be announced next year, and would also form the basis of the company's early-access users.

Although Hooey said he thought the technology could be complementary to next-generation sequencing, the company could still face competition from benchtop sequencers such as the Illumina MiSeq and the Ion Torrent PGM, particularly as prices continue to fall and run times become faster.

Already, both platforms have demonstrated their ability to rapidly sequence and identify Escherichia coli. Researchers at BGI and the University of Munster used the PGM to become the first to identify the E. coli strain responsible for the outbreak in Europe this summer (IS 6/7/2011), and public health officials around the world have begun discussing the possibility of employing next-gen sequencing as a tool to monitor outbreaks (CSN 11/2/2011).

Nevertheless, Hooey said Pathogenetix's platform would still offer advantages over next-gen sequencing in terms of speed and cost. In a clinical setting, for instance, the system could analyze a patient sample in hours for a cost of $25 to $50 in order to identify an infection-causing pathogen, he said.

Other potential competitors could be OpGen or BioNano Genomics, which both offer genome-mapping technology, but Hooey noted that Pathogenetix is addressing different applications than these firms.

For example, OpGen is focused mainly on creating optical maps to help in genome assembly from any organism, while Pathogenetix deals only with microbes and is "focused on working with complex samples to profile the composition, or find the needle in the haystack," he said.

BioNano Genomics, meantime, is developing a nanochannel platform that would visualize single molecules of DNA with first applications expected to be in de novo assembly and structural variation analysis.

Have topics you'd like to see covered by In Sequence? Contact the editor at mheger [at] genomeweb [.] com.