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Following Cartagenia Buy, Agilent Targets Cell-Free DNA Market With New Software Launch


NEW YORK (GenomeWeb) – Agilent Technologies recently launched OneSight, its first product for the bioinformatics market since the company purchased Cartagenia last year.

Agilent's OneSight software, which helps researchers visualize and explore chromosomal and sub-chromosomal aneuploidies in cell-free DNA sequencing data, is also the first standalone software platform developed for that purpose. The company launched the software following a six-month beta program that involved 10 institutions including researchers at Emory University. It described the solution at the American College of Medical Genetics and Genomics' Annual Clinical Genetics Meeting held in Tampa, Florida last week.

In a conversation following the announcement, Herman Verrelst, previously Cartagenia's CEO and now vice president and general manager of Agilent's genomics solutions and clinical applications divisions, told GenomeWeb that OneSight had been part of Cartagenia's development pipeline for some time prior to the company's acquisition by Agilent and was actually in development when the company was bought.

Cell-free DNA is "a very promising market" with applications in fetal abnormality screening and liquid biopsy-based tumor testing. "Over the past few years, it became clear that there was a huge need for a software platform that enables users to easily analyze NGS data generated on cell-free DNA without being locked down to one specific interpretation algorithm for a specific set of chromosomes," he told GenomeWeb.

Offering something that's general purpose means that Agilent can assess the different ways that customers use the software and potentially develop more targeted applications in the future, Verrelst added. Customers have so far used OneSight to reanalyze NIPT data to better understand samples that previous solutions have deemed high risk, for example.

"They are also evaluating the occurrence of false-positives, [such as] segmental copy number variations and true positives … and assessing the overall quality of their samples using our quality score," he said. Other clients in the oncology domain use the software to analyze liquid biopsy cancer samples to locate portions of the chromosome that are amplified and/or deleted.

OneSight's launch also fits in with Agilent's broader product roadmap. The company has an "active program" to come up with targeted platforms and applications for clinical research and more targeted clinical diagnostic applications," Verrelst said. "Bioinformatics and software are an integral part of that go-to-market strategy. It's the very the reason why Cartagenia was acquired by Agilent."

So far, the cloud-based software has been tested on data from Illumina and Thermo Fisher Scientific sequencing instruments only but the developers designed it to be agnostic to sequencing technology and compatible with most common NGS library prep kits. That flexibility is one of OneSight's main advantages, according to Verrelst.

"You can do this type of analysis using mainstream equipment and reagents and ultimately come to results by solely relying on the software," he said. This makes putting together a cell-free DNA-based pipeline a more cost-effective prospect for labs since they don't have to invest in specialized equipment or kits. Also, customers can define a set of reference samples generated using their preferred kit and platform, and they can change these reference samples if they switch to an alternative kit or platform, he added.

In terms of features, OneSight provides fine-grained graphical plots of chromosomal and sub-chromosomal abnormalities that make it easier to spot and differentiate between aberrations. The software also includes tools for calculating different statistics across chromosomes and for filtering technical noise and biologically irrelevant loci in sample datasets. Users can choose between multiple statistical parameters and define their own decision and classification rules for chromosomal and sub-chromosomal aneuploidies across chromosomes of interest.

"The graphical aspect is a key thing here," Verrelst said. "Other software might be very numbers-driven or targeted at a subset of statistical parameters, [but] we thought it was interesting to give users the [ability] to zoom in and out on specific aspects." In addition to that, "a number of statistical parameters are calculated and visualized across the chromosomes," he added. "It gives you a very detailed insight into those statistical parameters across all the chromosomes allowing even sub-chromosomal analysis."

Katie Rudd, an assistant professor in the human genetics department at Emory University School of Medicine, tested OneSight as part of a beta run for the software. Rudd, who is a cytogeneticist and director of Emory's clinical diagnostics lab, presented her findings at the ACMG meeting last week. She and her colleagues evaluated the software as part of their ongoing efforts to develop an assay for non-invasive prenatal screening. "Our goal was to really think carefully about the bench part of the assay as well as the software part of the assay, because we all know there is a ton of false negatives and false positives that can come out of this screen," she said told GenomeWeb.

Rudd and her colleagues already use Agilent's microarrays for pre and postnatal testing, and they were also familiar with Cartagenia's cytogenetics software. They already perform invasive testing but are just now starting to look into offering NIPT as well. "When they approached us about this particular tool, we really wanted to try it out as we are thinking about the best ways for us to build a pipeline," she said.

For the beta run, the Emory team partnered with researchers at Victorian Clinical Genetics Services (VCGS) at the Royal Children's Hospital in Melbourne, Australia. Researchers at VCGS had already analyzed Illumina sequence data from more than 5,000 prenatal cell-free DNA samples from pregnant moms using a different analysis pipeline. As part of a pilot, researchers at both institutions analyzed a subset of that data — about 200 normal and abnormal samples — using Agilent's OneSight and then compared the results with those obtained by the VCGS tool.

"OneSight makes calls on trisomy and monosomy, increased risk for trisomy, increased risk for monosomy, or normal across each of the 22 autosomes," she explained.  In addition, the team went through and manually curated each of the 200 samples to better understand the aberrations that OneSight called. "Is this a full trisomy [or] is this a segmental trisomy? We liked OneSight because you can really visualize that," Rudd said.

According to Rudd, OneSight did as well as the VCGS pipeline on the samples, returning most of the same results. Specifically, the researchers were able to detect the eight trisomy 13 cases, the three trisomy 18 cases, and the 34 trisomy 21 cases in the 200 samples. There were two samples that the VCGS pipeline tagged as intermediate risk for trisomy 21, however, that OneSight did not detect initially until the researchers adjusted some of the software's settings. 

"The way OneSight works is it compares each chromosome within each sample to a reference set of 100 normal samples, and so we found that some of those normal samples that had just been randomly chosen were kind of noisy and so we revamped the reference dataset to make the reference data for chromosome 21 less noisy," Rudd explained. "We also changed our cutoffs for the abnormality scores for all the chromosomes and not just chromosome 21."

After they changed the reference datasets, OneSight successfully tagged the two samples as increased risk. As it turns out, one of the samples had a low fetal fraction — approximately 2 percent — which likely accounted for the uncertainty around the sample and result in its being tagged increased versus high risk of trisomy 21. An invasive follow-up test confirmed that it was indeed a full trisomy case.

For the second sample, the fetal fraction was much higher — about 12 percent — but no further testing was done. In that case, the child was born healthy with no diagnosis of Down's syndrome, suggesting that the first result was likely a false positive, but "we don't know," Rudd said.

One of the main benefits of OneSight is its visualization capabilities, which makes it possible to identify the type of chromosomal abnormality that the fetus has. "I've seen in this field reports from other laboratories where something is reported as increased risk for trisomy for chromosome 3, [but] it doesn't tell you if it's the whole of chromosome 3 or part of chromosome 3," Rudd said. "There's not just trisomy and monosomy. There's all sorts of segmental chromosome rearrangements that we are going to be detecting in fetuses with abnormalities, [and] actually being able to visualize those calls ... gives you a lot more information that you really need to interpret the abnormality in the cell-free DNA sample."

That sort of knowledge could be very informative for families. For example, in one of the samples analyzed as part of VCGS partnership, the researchers identified a fetus that was at increased risk for trisomy 3 but were also able to see that the trisomy was confined to the latter half of the long arm of chromosome 3 and that it was an unbalanced translocation. Follow-up testing done on a sample from the mother showed that she carried a balanced form of the translocation.

"That is far more informative than just saying you have increased risk for a particular chromosome being trisomic," Rudd said. "This actually tells you not only the type of rearrangement that could be going on in the fetus but also that you need to consider testing the parents for a balanced form of this, and that could be important for future pregnancies and for other family members."

Agilent plans to charge per sample, with the exact prices varying depending on how many samples the customer wants to analyze. Depending on the volume, the company will charge between $20 per sample and up to $100 per sample.

For now, Agilent is offering OneSight as a standalone solution but it is exploring opportunities to bundle the software with reagent and library preparation kits. Cartagenia has also handed over the sales of its existing portfolio, which includes the Cartagenia Bench Lab CNV software, to Agilent's genomic salesforce. Since the transition, sales of the Cartagenia portfolio have spiked, according to Verrelst. 

"Where before we were a small company with a smaller reach, being a part of Agilent gives us a much broader access to the market," he said. At the moment, the Bench Lab platform is still being sold as a standalone software, "but we are looking into opportunities to bundle this ... with some of the other products of Agilent in terms of providing more end-to-end workflows or to make it more attractive from an economic perspective."