CHICAGO – From tragedies often come life-saving innovations.
ICBiome, a five-year-old bioinformatics firm based in Sterling, Virginia, grew out of one such tragedy.
CEO Srini Iyer was a consultant in business intelligence (BI) technologies who was detailed to the National Institutes of Health's Clinical Center in Bethesda, Maryland, for nine years, where he led design of the research hospital's BI system. During that stint, in 2011, there was an outbreak of carbapenem-resistant Klebsiella pneumoniae at the center that led to the death of 11 patients.
NIH researchers turned to whole-genome sequencing to track and eventually control the outbreak, and the experience gave Iyer the idea for a business. He launched ICBiome in 2015, and the company set its focus on a more common hospital-acquired infection (HAI): methicillin-resistant Staphylococcus aureus.
Hospitals routinely collect DNA samples when they screen patients for MRSA and other pathogens, particularly in intensive care units, including neonatal ICUs, and they keep the samples.
"What we are trying to tell hospitals is … let's sequence [the samples] to understand are there any clusters there that you didn't know about?" Iyer said. "This is a much better way of looking at it than trying to resolve an outbreak once it starts."
WGS data is more accurate than older technologies like PCR and pulsed-field gel electrophoresis. Iyer said that false positives can lead to unnecessary shutdowns of ICUs and other hospital units, a problem that WGS prevents so hospitals can target their mitigation efforts.
"A lot of the big hospitals are doing biobanking," Iyer said, but not many are using those samples efficiently for infection surveillance. If one swab tests positive for a pathogen, ICBiome can go back and look at other samples from previous month or two or three to see if there might be an outbreak cluster, according to Iyer.
"We believe this is going to become the norm over the next two to five years because the cost of sequencing is going down tremendously," Iyer said. Currently, he sees access to sequencing and microbiome analysis as the greatest barrier to this happening, and believes that ICBiome's products can help hospitals overcome this.
ICBiome recently wrapped up the evaluation of a NICU. According to Iyer, PCR on 25 biosamples produced an entirely different phylogeny than WGS. "We actually found a [MRSA] cluster they didn't know about," Iyer said. "If there is a transmission, chances are you will not know about it unless you do sequencing."
The startup has not had any of its data published in peer-reviewed journals, largely because it just wrapped up its SBIR work and is still in the process of obtaining patents for its technology, according to Iyer.
Funded by more than $1 million in federal and state grants since its inception, ICBiome relied on an NIH Small Business Innovation Research award to develop its flagship technology, called BiomeMRSA. That software can analyze WGS sequences and return results within four hours to help hospitals and public health agencies catch outbreaks early or even prevent infections in the first place.
Last year, ICBiome participated in an NIH Innovation Corps (I-Corps) program for recipients of Phase I SBIR and Small Business Technology Transfer awards. Following that eight-week program, Iyer said that the company evaluated the ICU at one hospital and the NICU at another. ICBiome had discovered previously undetected MRSA outbreaks at both sites.
CTO Dante Martinez joined ICBiome a little more than a year ago after working in data and analytics in other industries for more than 20 years. He had worked with Iyer at data analytics giant MicroStrategy early in his career, and decided to move into bioinformatics when he learned about an infection outbreak in a NICU that killed three babies and sickened five more.
By looking at the outbreak at the genome level, ICBiome was able to help the hospital understand how infections spread, and then take appropriate actions to prevent further tragedies.
"This [technology] has really big impact in society," Martinez said. "Being able to save even one life, it's very satisfying."
ICBiome uses Illumina's BaseSpace informatics platform to acquire and manage data. Sequencing labs upload their outputs to BaseSpace, then ICBiome pulls the data into its analytics pipelines on the Amazon Web Services cloud.
The company recently completed an integration with Amazon QuickSight analytics technology to serve as a dashboard for clients to track the movement of deidentified data and visualize ICBiome's results.
"It will tell you the timeline, how the samples are collected, the clusters in the samples, and how they're correlated," Iyer said.
Martinez said that the company chose QuickSight for its security and because the Amazon platform is modular, charging by the user rather than asking for a blanket access fee up front.
Through BiomeMRSA, hospitals receive results in a secure environment, including analyses by QuickSight. The facilities then can run further analysis with ICBiome software on their own IT infrastructure.
The modularity of QuickSight and AWS in general allows ICBiome to scale, which came in handy when the COVID-19 pandemic hit the US.
"Back in March, we decided to plunge into COVID because we saw that this as a perfect fit for us," Iyer said. The company quickly modified its core technology to create an app called BiomeCOVID and is building a data analysis pipeline for coronavirus sequences.
Since then, ICBiome has loaded and analyzed more than 100,000 SARS-CoV-2 genomes from public databases in the US and Germany on its AWS cloud space. Iyer expects to have 1 million publicly available coronavirus genomes to draw from in the next year or so.
"We just discovered a lineage from Texas that moved to Michigan about two months ago. I don't think anyone knew about that," Iyer said. "Those are the kind of insights we can provide by leveraging the data analysis that we have known from other verticals."
A spokesperson said that ICBiome is creating a new video about the spread of the Texas strain that likely originated in May. The company also is working on a video about global movement of the highly transmissible D614G mutation of SARS-CoV-2, with the goal of informing epidemiological research.
"We really want to start providing content on these mutations so that if you're a lab in Texas or a lab in Washington, you don't need to invest in hardware and software for analysis," he said. Those labs will be able to download the mutation dataset from the ICBiome platform.
"We are trying to shift away from researchers having to figure out the end-to-end analysis," Iyer explained. Rather, he would like researchers to be able to see where else certain mutations have been found.
"That is where I think the trend is going," Iyer said of disease surveillance in general. "We are shifting to a post-COVID world where genetic sequencing is going to come to both viruses and bacterial transmissions over the next five to 10 years."
ICBiome only wants to be an informatics company, though. Iyer said that sequencing has become a "marketplace," though he stopped short of calling it commoditized.
"We can leverage any vendor that may do sequencing, so we can either directly work with hospitals or we can work with sequencing providers," he said.
Iyer said that COVID-19 has made the sales process more difficult for the company because hospitals and health systems have seen cash flow dry up from postponed or canceled elective procedures, but that challenge has created an opportunity.
"I think this COVID work we're doing and the MRSA work we're doing are all great steps for us in trying to confront this pathogen issue that we were working on before COVID started," Iyer said.
"When we started, we really had one major goal, to bring pathogen genomics to hospitals that are looking to contain the pathogens," Iyer added. That is still the goal, though the focus is broadening.
The firm is building a new product, called BiomeMDR, for multidrug-resistant bacterial pathogens, and hopes to have it out by April.
BiomeMDR, which will address other pathogens, including like E. coli or Enterobacter, is the result of hospital-based epidemiologists asking for help detecting outbreaks of more than just MRSA, according to Martinez.
"Multidrug-resistant pathogens are not going to go away," Iyer said, noting that the Centers for Medicare and Medicaid Services (CMS) has been penalizing US facilities that show high rates of HAIs, including MRSA and Clostridium difficile.
CMS updates its HAI list monthly, so ICBiome offers one-month programs for identifying and mitigating outbreaks, particularly in critical care units. "For the really big hospitals, we want to do routine surveillance," including the installation of a MRSA dashboard to track the growth and movement of infections in multiple wards, Iyer added.
The clusters of COVID-19 deaths related to long-term care facilities also opened Iyer's eyes to the technology's potential in nonacute settings.
"I think you're going to see diagnostics shifting to nursing homes and long-term care facilities as newer markets for us," Iyer said.
ICBiome does not have to chase the LTC market directly, but can work through sales partners. "[Facilities] can go through the channels that already have products for those places and we just have to put an add-on for whole-genome sequencing," Iyer said.
He said that ICBiome also looking to build a local plug-in to its own cloud-based data store to facilitate quick analyses of why pathogen transmissions might be happening.
"We want to simplify postsequencing analysis and the final integration where you take the results and go to the metadata and try to understand what is happening with these particular samples," Iyer said. "It's transmission-focused, both post-outbreak and pre-outbreak, as well as for routine surveillance."
He predicted that there will be an "incredible increase in awareness of infectious disease diagnostics" after the COVID-19 pandemic passes.
But ICBiome does not want to be a point-of-care diagnostics company per se, but will move into that area as whole-genome sequencing grows in the POC arena.
"As there are more and more culture-free point-of-care diagnostics that are coming through, there is a need for [health systems] to invest in culture-based analysis to understand what's in their hospitals," Iyer said. "We believe that's our sweet spot."