NEW YORK (GenomeWeb) – Cypher Genomics this week launched an updated version of its data analysis software for the automated interpretation of genetic variants in cancer applications.
The original version of the software, called Mantis, was made commercially available a year ago for interpreting germline data. This past January, the firm inked a deal with Sequenom for the use of Mantis to analyze clinically relevant fetal sub-chromosomal variants detected in maternal blood. With the launch of the new version, researchers will be able to use the software to detect cancer-related somatic variants.
Mantis is based on technology licensed by Cypher from Scripps Translational Science Institute, Scripps Health, and the Scripps Research Institute. The San Diego-based firm has been developing, validating, and beta-testing the technology for the last several years.
According to the firm's President and Chief Operating Officer Adam Simpson, Cypher's focus is to enable clinical laboratories to develop differentiated content. In doing a deal with Sequenom, it purposely chose to address the fetal space first because the non-invasive prenatal testing market "is by far" the area where next-generation sequencing currently has the most clinical volume, he told GenomeWeb.
Meanwhile, though, clinical applications of NGS technology in cancer continue to increase, and "it's really important for us to support that market," with Cypher's technology, Simpson said. "And we're simply applying that to this market in both the somatic side, as well as circulating fetal DNA."
The updated version of Mantis, which was launched at this week's American College of Medical Genetics and Genomics meeting, provides a summary of somatic and germline variants for single nucleotide variants and small indels. The software also clarifies variants of unknown significance that are difficult to classify, Cypher said. Mantis accepts either tumor-normal variant calls or somatic calls, and the resulting information provides insights into the pharmacogenomic impact of anti-tumor drugs, it added.
A feature of the software is its ability to analyze a whole genome, allowing researchers to decipher the importance and relevance of currently unknown variants. Since development of Mantis began, the goal was to make it useful for whole-genome interrogation, Cypher CEO Ashley Van Zeeland told GenomeWeb, adding that the market has now reached the point where such work is feasible.
"The differentiator is really our technique to move beyond a couple hundred of your favorite genes that are [done] primarily manually, to using data-driven approaches to interrogate these whole genomes at the same time," she said. With the update, "the idea is rather than only supporting annotation for known cancer variants, we're trying to enable new discoveries of additional cancer variants in cancer genes and beyond."
Cypher has an extensive catalogue of well-curated, well-known cancer genes and variants, but Mantis further elucidates the potential consequences of novel mutations, so if a researcher sees a mutation in a hotspot region that's not in the Catalogue of Somatic Mutations in Cancer database, for example, he/she can evaluate its importance.
Cypher aggregates data from more than 50 sources, including proprietary reference populations, such as the Scripps Wellderly Genome Resource, which contains whole-genome sequences from hundreds of participants in the Wellderly Study, an ongoing research project at STSI to identify genes associated with lifelong health.
Using proprietary algorithms, Cypher cleans up well-known false positives in the literature and predicts the pathogenicity of variants that have not been reported in the literature, a Cypher spokesperson said.
Mantis' workflow is similar to some other data analysis tools. A sample, either by traditional biopsy — or eventually liquid biopsy as that technology takes off — is sequenced. Variants, either from somatic calls or from tumor-normal variant calls, are submitted to Cypher's secure cloud platform, and a fully automated annotation and interpretation analysis is returned to the researcher with a fully prioritized list of which variants matter, "so unlike having to a priori decide which variants" may be important "we take the whole genome's worth of information and do that for our partners," Van Zeeland said.
In the fall, Cypher ran a trial access program for researchers interested in Mantis. According to Van Zeeland, the firm saw "great participation" in the program. Simpson added that Cypher anticipates running a similar program for the new version of the software.
Mantis is available via a partnership model with Cypher, similar to its NIPT deal with Sequenom. The product is platform-agnostic and can be used with any NGS instrument.
Also at the ACMG meeting taking place in Salt Lake City, the firm is presenting data on the accuracy of Mantis for interpreting CNVs in the fetal space. According to the study's abstract, Cypher compared 91 CNVs — comprising both duplications and deletions spanning a range of about one to 77 megabases in size — to a "consensus opinion of experts."
The initial expert review led to 59 CNVS being classified as pathogenic or potentially pathogenic, with the remaining 32 considered variants of unknown significance. Cypher said that a comparison of expert opinion with classifications produced by Mantis "suggests a high concordance of the automated interpretation with expert review, providing a scalable and automated solution to reporting clinically relevant CNVs."