Tailoring genomic services with custom QIAGEN workflows

In 2019, Scott Grist, Ph.D. and Rachel Hall decided to plunge into launching their own company. Grist and Hall had been running a government diagnostic lab in Adelaide, Australia as head of molecular pathology and lab operations manager respectively. “We had thrown the idea around before, and we just wanted to do the work and not worry about politics,” says Hall. They quit their jobs, took their severance pay and used it to found the private genomic services company GNOMIX.

Getting started during a pandemic was a struggle. Lockdowns meant huge delays. Equipment that had been ordered didn’t arrive, everyday consumables were in short supply and their lab accreditation applications went unprocessed; they could not get experts to service their equipment. Since many universities had also shut down, there was very little work, and hence revenue, coming in.

They signed up their first customer mostly based on hope. “We were saying ‘yes yes’ on the phone, but behind the scenes we couldn’t even process samples yet,” Grist recalls. As soon as their QIAcube extractor, QIAgility liquid handlers and other equipment arrived, “we hit the ground running,” says Grist.

They initially had only low-throughput equipment and had it constantly working around the clock on split-shifts for about a month. But they managed to meet their deadline. Meanwhile, the company continued to score additional clinical trial projects, which were not broadly shut-down during the pandemic and this became the company’s “bread and butter,” says Grist.

Today, the company is thriving. “We specialize in not specializing,” says Grist, who has worked as a molecular pathologist for four decades. GNOMIX provides “bespoke” solutions to customers trying to answer specific questions.

Tailored therapies

What sets GNOMIX apart from competitors is their hands-on approach. “Sometimes customers know exactly what they want,” explains Grist, “other times they have a vague idea and need some help to articulate their thoughts.”

GNOMIX provides services ranging from primary processing of samples to bioinformatic analyses. “Our point of difference is we ask ‘what’s your question,’ and then we’ll work out an end-to-end solution.”

The majority of GNOMIX’s business comes from research and trials engaged in safety and efficacy studies of investigational drugs. The explosion in available technology to analyze tissue samples can provide researchers with valuable insights, empowering them to develop new therapies that are more effective because they are tailored to a person’s specific type of disease or genes.

The GNOMIX team’s  favorite part of the jobs is coming up with novel solutions, especially when the end result improves the science and benefits patients. For example, one customer wanted to investigate gene expression of five to six genes to understand how a drug alters gene expression for a phase 1 clinical safety trial. Grist and Hall began a conversation about the study with the customer, which led to a discussion about off-target effects of the drug. The GNOMIX team then suggested a panel for studying the expression of 200 genes to investigate whether the drug was also having an effect on the body’s inflammatory response.

“The customer didn’t ask at first because they assumed the cost for this bespoke service would be astronomical,” Grist recalls. “But we were able to offer them the more comprehensive assay for the same price.” In the end, the strength of the study was hugely improved because the researchers were able to look at inflammation markers, as well as their intended drug targets which was “very rewarding,” adds Hall.

Dealing with challenging samples

One challenge that GNOMIX is facing more frequently is poor sample quality or dealing with a variety of sample types. “Clinical trials, particularly oncology trials, are conducted with people who are quite ill, possibly terminally so. From an ethical standpoint, the study minimizes the samples we can take,” explains Grist.

“We have to create ways to get the best use out of minimal specimen, often needing multiple assays,” says Grist and “every study is different.” Many other genomic services companies are unlikely to be able to provide such tailored solutions, he adds.

The GNOMIX team chose QIAGEN Kits and equipment precisely because the products cover their entire workflow. “Having extraction protocols is very important. As we gain more experience, PCR testing becomes less challenging. Translation sciences are becoming more commercial, and everyone wants things to be routine. We are often the first to introduce automation in these processes, which is where our interplay with the QIAGEN Kits and equipment also comes into play. It’s something we can create protocols for, and labs can pick up and adapt.”

“’What’s the best extraction method to use with that device?’ We don’t have the time to do a lot of optimization,” says Hall. QIAGEN’s “Sample to Insight” solutions mean that the equipment required for every step of processing and analysis of samples has already been tested and optimized as an entire workflow. “We can start an analysis with reasonable confidence that we can just follow the instructions and it will work fine.”

This is important when turnaround times are tight – they simply can’t afford to be held up by optimization issues, says Grist.  Once GNOMIX was negotiating for a year with a customer, for example. When they finally got the contract, “they asked us to process the samples and deliver results within a week,” Grist recalls. “We couldn’t have accomplished that if we had to tune up our workflow.”

The workflow

To investigate gene expression, GNOMIX relies on the QIAseq UPX 3' custom gene panel and transcriptome kits. Another common application of the transcriptome kits is to analyze blood samples for changes in gene expression at specific time points after administering a drug. “Transcriptome expression work is quite big in clinical trials, many people have been happy with the results,” says Hall.

In addition to the transcriptomic analysis kits by QIAGEN, other workhorses in the lab include the QIAGEN TissueLyser to prepare samples for genomic analyses and the QIAsymphony robot for high-throughput automated extraction. To assess sample quality and purity, they use QIAxpert and QIAxcel instruments. Downstream analyses are setup using QIAgility liquid-handling robots for QIAseq NGS libraries or QIAcuity digital PCR assays.

Another recent addition to the lab has been the QIAcuity Digital PCR System. “When we saw this system, we knew we just had to have it,” says Grist. GNOMIX has many requests for sensitive and accurate quantitative work, that just can’t be done any other way than qPCR or digital PCR (dPCR).

The GNOMIX lab has always favored the digital principle, Grist adds, but had held back because of the technical challenges and cost of providing it as a routine service. “I had worked with digital for many years, going right back to the pioneering days with Alec,” recalls Grist, referring to Professor Alec Morley, one of the inventors of the concept. “It was wonderfully accurate but always a lot of work to get it right. But now the QIAcuity just makes it so easy and reliable.”

“To assess how gene expression is changing, you want to focus on the 10, 20, 30 or 40 genes. High sensitivity will help the client zero in on what they are looking for.”

Within a few weeks of setting up the dPCR system, GNOMIX had built and implemented robust tests for viral load, gene copy number variation in oncology and gene/exon deletion assays. 

They also use dPCR for RNA and DNA quantitation from environmental samples, detection of mRNA in extracellular vesicles and more. “The applications are really limitless. Regular PCRs and qPCRs just transition so easily onto the QIAcuity, that you just want to use it instead,” says Hall.

Right now, 80% of the company’s business comes from clinical trial work, mostly conducted in Australia, for international sponsors. But GNOMIX hopes to expand their services to other applications and more directly to international customers. “Scott is extremely well connected and well known,” says Hall. And as word has spread among customers, GNOMIX is garnering more inquiries.

Despite the challenges of running a business, Grist reflects, "I’ve never felt that we made a bad decision." Transitioning from a role with more direct patient impact in the public health services lab  to developing new therapies is simply a shift to a different way of helping. Hall notes that their current focus brings them just as much satisfaction as before, just a different sort. “It’s all about the work now and not about the politics.”