NEW YORK (GenomeWeb) – French informatics company Life and Soft is continuing to build its business after publishing a study earlier this year that provides a hint at the types of discoveries it hopes to enable in genomic diagnostics.
The study, published in March in Scientific Reports, offered a proof of concept for a novel method of detecting cytomegalovirus in pregnant women undergoing non-invasive prenatal testing — supporting the possibility of an easy informatic add-on to existing clinical NIPT.
Life and Soft currently serves clients mainly in Europe, but Founder and Director Eric Ginoux said this week that the company is interested in expanding to the US if it can establish the right inroads over the next few years.
The firm offers general informatics services — mainly in next-generation sequencing analysis and biostatistics — and has also created a handful of software tools, including packages designed for cancer sequencing, microbial detection, non-invasive prenatal DNA analyses, and CRISPR gene editing.
Providing solutions for clients that want or need to outsource certain aspects of their genomics workflow is nothing new, but as the medical field increasingly embraces genome sequencing, demand for technology to parse and systematize genomic data continues to grow.
Ginoux said that unlike firms focused only on feeding that beast, Life and Soft's strategy is to use its services business to support its own internal R&D efforts, with the goal of pinpointing and realizing novel diagnostic strategies, such as the cytomegalovirus work published this spring.
Virginie Chesnais, Life and Soft's project manager, said that the NIPT viral detection study emerged from work the firm had done with a client to develop an NIPT platform.
This resulted in a challenge: What might be done to add value to a standard NIPT offering, or what else might be gleaned by the data produced by the sequencing used in these tests?
In the study this spring, Chesnais, other colleagues from Life and Soft, and academic collaborators from two French hospitals showed that they could determine a plasmatic viral load with a 10 copies/mL threshold, using the same (relatively low-depth and low-cost) sequencing data generated for standard NIPT.
Maternal infection with human cytomegalovirus (HCMV) during pregnancy can cause congenital infections that cause severe complications for newborns. The virus has also been implicated in adverse outcomes even in cases where there is no transmission to the fetus.
The Life and Soft team hypothesized that using the whole-genome sequencing data from NIPT, they could detect and quantify circulating viral DNA in pregnant women.
The aim would not be to replace serologic or any other existing molecular tests, but rather to provide a way to raise an alert for the risk of a viral infection via the increasingly standard practice of blood-based prenatal aneuploidy testing.
In case of a suspected maternal infection, the clinician could then provide appropriate confirmatory testing and follow up.
The method the company developed uses human unmappable reads from NIPT sequencing to search for viral specific sequences and quantify absolute viral load.
After a variety of experiments using contrived samples, the team validated the approach in a cohort of 538 pregnant women who were part of a study called EPOSA which is evaluating blood-based DNA trisomy 21, 18 and 13 screening using massively parallel sequencing methods modified from those developed by NIPT firm Sequenom.
The authors wrote that an average of 77 percent of reads for each woman were correctly aligned to the human genome and discarded for the rest of the HCMV analysis. After sample alignment to the HCMV genome, the investigators then calculated the viral depth for each sample.
Two samples demonstrated a depth above the threshold that the team had defined, suggesting the presence of circulating HCMV DNA. Out of 15.9 million and 16.1 million reads in these two individuals, the method detected 11 and 12 reads respectively that mapped to the HCMV genome.
The team was also able to collect some data that their methodology could be applied to a variety of viruses, not just cytomegalovirus. For example, 369 patients in the cohort had available results from immunologic tests for HBV virus, three of which were positive.
When the Life and Soft team mapped these samples' reads against the HBV reference genome, they were able to identify two as having a mean viral DNA depth higher than the positive threshold.
Chesnais said that the results provide a first hint of feasibility for a two-birds-with-one-stone approach combining NIPT screening and prenatal viral infection. But she and Ginoux cautioned that for this to move into the clinic, it will require significant further validation to meet European regulatory requirements.
Life and Soft has obtained a CE mark for its oncology toolset, called Onco LifePipe, but its solutions for NIPT and for microbial detection are currently for research use only.
"We saw that there was a real value in this data," said Ginoux. "And so we are developing a real solution that we hope can be used as a diagnostic tool, but that still requires more work on the … regulatory side," he explained.
Akin to the NIPT viral detection application, Ginoux said that the company is also conducting research into novel solutions for viral detection in the field of transplantation.
And as it works to make its prenatal and microbial toolsets available in Europe for clinical use, Ginoux and Chesnais said that Life and Soft has also been conducting in silico work aimed at various aspects of nanopore sequencing analysis.
According to Chesnais, the company hopes to be able to start performing its first experiments using human samples for this application by the end of this summer.