NEW YORK (GenomeWeb) – New York startup Biotia aims to help hospitals cut down on infections by providing them with a DNA sequencing-based microbial surveillance service and targeted interventions.
The company was founded a year and a half ago by Chris Mason, an associate professor of physiology and biophysics at Weill Cornell Medicine; evolutionary biologist Niamh O'Hara, Biotia's CEO; and computational biologist Rachid Ounit, the company's CTO.
In 2015, O'Hara, who holds a PhD in ecology and evolutionary biology from Stony Brook University, was accepted into the Runway Startup Postdoc Program of the Jacobs Technion-Cornell Institute, which provides funding and assistance for postdocs wanting to start their own business.
This summer, Biotia is looking to raise seed funding on the order of $2 million to $3 million, followed by a Series A financing round sometime next year.
In 2015, Mason's group published a study for which they surveyed the microbiome of the New York City subway system, a project the researcher had started two years prior. The company is building on the same approach, metagenomic profiling of surfaces, applying it now to hospitals.
Currently, about 4 percent of hospital patients acquire an infection during their stay, O'Hara explained, and at least 10 percent of them die of the infection. Many patients get infected from the environment, she said, despite frequent cleaning. Doctors "don't really know what's in the hospital until a patient gets sick and they test the patient," she said. "We're trying to move that up, testing the environment and catching these pathogens before the patient gets sick, and helping with targeted interventions."
Hospitals currently do not regularly monitor their environment for pathogens, O'Hara said, because no technologies exist that are fast and cheap enough. Periodically, they will monitor surfaces using microbial culturing, which is the current gold standard but is slow and does not identify all microbes present. Another approach used by hospitals is ATP testing, which measures growing microorganisms quickly through the detection of adenosine triphosphate but cannot identify them.
A metagenomics approach, she said, would be faster than culturing and be able to identify antibiotic resistance and population dynamics. This would allow hospitals to clean contaminated areas more thoroughly, for example.
To be useful for cleaning interventions in a hospital setting, monitoring would need to be done within 24 hours or less, O'Hara suggested. The goal is to reduce the turnaround time to four or five hours, Mason said, and ideally, to less than an hour. "We think with a variety of improvements in sequencing technology, we can get there," he said.
Right now, sequencing and analyzing surface samples takes more on the order of 24 to 36 hours, using standard protocols that have not been optimized for speed, Mason said.
So far, the company, which is housed with other Runway Startup firms in a building shared with Google in the Chelsea neighborhood of Manhattan, has been working on improving sample prep, sequencing, and data analytics, focusing on both speed and accuracy.
For example, it has been developing methods for extracting more DNA from swabs, and faster transposase-based sample prep protocols.
So far, the firm has been using Illumina paired-end shotgun sequencing, performed either by Mason's laboratory or by outside contractors, and is developing a targeted sequencing panel. While the latter could identify species and strains, whole-genome sequencing can tell more about things like antibiotic resistance, or whether a population is under selective pressure, O'Hara said.
The company is not wedded to a particular sequencing platform, though, and would consider using nanopore-based technology, for example, which promises to be faster, if the per-base accuracy improves sufficiently.
On the informatics side, Biotia has been developing proprietary software that uses an approach similar to that of a metagenomics analysis tool called Classifier based on Reduced K-mers (CLARK), which Ounit helped develop as a graduate student at the University of California, Riverside. Ounit explained that the microbial databases the software uses to compare sequence reads against have been growing over the years, so it needs to be able to process more information faster, while providing good accuracy.
Biotia is currently conducting pilot projects with two hospitals, NewYork-Presbyterian, which is affiliated with Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center, and has been working with their respective infection control departments.
For the pilots, the company has been analyzing samples from patient rooms, comparing its results side by side with those from culturing and ATP testing. Mason said he has already presented initial results internally, identifying "things you would expect to find in hospitals."
The focus is on high-risk areas of hospitals, O'Hara said, for example rooms occupied by immunosuppressed patients, who are more vulnerable to infections than others.
In addition, the company is testing new ways to clean hospital rooms with collaborators. "We don't just want to be purely a detection group," Mason said. "It's obviously very useful to know what's there, but we also want to embed with that ways in which you can immediately address the problem."
Not all experts believe the company's approach will be useful for cutting down hospital infections. Jack Gilbert, director of the Microbiome Center and a professor of surgery at the University of Chicago, said that hospital cleaning companies want to know whether they have successfully removed dangerous organisms, but metagenomics cannot provide that information because it only identifies the presence of DNA, not that of living microbes. "It doesn't provide you with the evidence you need to make a specific claim," he said. "The only way to do that is to culture these organisms and say, 'yes, there is a reduction in the viable pathogens associated with the surface material.'"
He also said that the current timeframe for metagenomic analyses — in his hands, on the order of two to three days — is not useful in practice because the microbial environment might have already changed by the time results get in.
Gilbert's group just published a year-long study in which they monitored the microbiome of surfaces, patients, and staff in a newly opened hospital in Chicago. The project involved metagenomic sequencing and allowed them, among other things, to identify organisms with antibiotic resistance. "What we were unable to do is provide any practical advice to the hospital environment based on that data," he said.
Mason countered that Biotia's current approach takes less than 24 hours, which he said is sufficient to prevent the spread of hospital-acquired infections in most contexts, and that it has piloted technology that takes less than 30 minutes. In addition, he said, DNA- and RNA-based methods are available that can distinguish between living and dead microorganisms.
Following the two current pilot studies, Biotia plans to charge for its services, offering them to other hospitals, starting in the New York area. O'Hara said hospitals can be challenging customers, since they are large, often slow-moving organizations with year-long sales cycles. However, Mason said the firm already has paying customers "in other healthcare-related contexts."
If the approach could indeed help to reduce the number of hospital-acquired infections, it could save hospitals considerable costs related to extended patient stays, O'Hara said.
In terms of competitors, others are already using genomics approaches to identify infections or antibiotic resistance in patient samples, for example OpGen, but O'Hara said she is not aware of any other company using sequencing to monitor hospital environments.
In addition to its pilots, Biotia has been collaborating with Mason's group on a large-scale nationwide metagenomics study of ambulances, involving more than 1,000 samples, that is currently under review for publication.