NEW YORK – This month's announcement that Oxford Nanopore Technologies would integrate its Epi2Me cloud-based analysis platform with Geneyx's software to automate analysis and clinical reporting of long-read sequencing data represents the continuation of an ongoing growth strategy for Israeli bioinformatics startup Geneyx.
Chief Product Officer Hagar Mor Shaked said that the Geneyx platform is already integrated with Illumina's BaseSpace and with Pacific Biosciences' SMRT Link software. "We pull the data [after alignment] and the users don't need to do anything, just to upload a metadata file like a batch output file," she said.
Geneyx offers a VCF uploader tool for users to import VCF files from any sequencer into its software platform, but that requires manual intervention. The firm has connected to Illumina and PacBio with an application programming interface. "The exact same flow is now under development with the Oxford Nanopore team," Mor Shaked said.
She said that the software is agnostic to the sequencing technology and can accept long and short reads of exomes, genomes, and gene panels. The Oxford Nanopore partnership is about integrating software and workflows to automate analysis.
Geneyx Cofounder and Chief Marketing Officer Raviv Itzhaky described this process as "one-click operation" that takes the burden off of genetic laboratories to manage bioinformatics.
Oxford Nanopore said in a statement that the integration would support loading, visualization, and annotation of nanopore data for newborn screening and for research and diagnosis of rare diseases.
The firms will kick off the partnership with a series of pilot projects to test the software in clinical settings. Mor Shaked said the technical integration would take several months, though she did not offer a timetable for a commercial launch.
Geneyx's technology relies on artificial intelligence powering genetic data analysis and interpretation to help improve risk assessment and risk prediction, and ultimately improve diagnostic yield. The firm currently has about 200,000 samples to train its AI on.
The internally developed algorithm correlates genes to phenotypes, then scores and prioritizes variants that might impact each patient. Mor Shaked said that the company frequently updates its knowledgebase for variant annotation.
Geneyx specializes in analysis of whole-genome sequencing, including long-read sequencing, as evidenced by the Oxford Nanopore partnership. Features designed specifically for WGS analysis include an enhancer analysis for all variants and an automated tool to compare copy-number variations to single-nucleotide variations. For long-read sequences, the software incudes methylation and phasing analysis.
Mor Shaked, who heads bioinformatics in the genetic department at Hebrew University of Jerusalem-affiliated Hadassah Medical Center, came across Geneyx about three or four years ago while trying to analyze WGS data in a pilot study of unsolved cases of monogenic disorders. She joined Geneyx a year and a half ago but remains a user at Hadassah.
Mor Shaked said that she used to have to run manual searches for compound heterozygous variants or to cross between large and small variants. "There is no reason for this to be manually done by our users for long-read sequencing," she said.
Target customers include standalone and hospital-based genomic laboratories as well as commercial genetic testing firms. One client in the latter category is German startup Arcensus. Mor Shaked said that Arcensus is more advanced than most because it conducts WGS for undiagnosed, severe rare diseases.
Chief Operating Officer Gabriela Oprea joined Arcensus in May 2021, about six months after former Centogene CEO Arndt Rolfs launched this new company. Rolfs stepped down as CEO of Arcensus earlier this year, handing the reins to another former Centogene executive, Shivendra Kishore.
Arcensus conducts WGS-based diagnostic, preventive, carrier, and pharmacogenomics screening on each sample it collects. Oprea said that an earlier software vendor was not able to meet the firm's complex analysis requirements, so the company is currently migrating to Geneyx.
Specifically, Arcensus wanted more flexibility and automation from its software to adapt to new American College of Medical Genetics and Genomics (ACMG) and ClinGen guidelines for copy-number variant interpretation. The firm needed "an AI-based algorithm which can run in the background and make my life easier," Oprea said. Geneyx is able to provide that.
Geneyx was founded in 2018 because of an incident involving the shared grandchild of Itzhaky and Cofounder and CEO David Yizhar. When Itzhaky's daughter was pregnant with the child of Yizhar's son, she received noninvasive prenatal testing.
The test results simply said everything was normal, but Itzhaky was not satisfied with the report. "They sequenced the mother, they sequenced the baby. There's a lot of data there. What are they doing with the data?" he wondered.
The geneticist who performed the test, Ofer Yizhar Barnea, had no answer either. Barnea, who is now a researcher at the University of California, San Francisco, became the third cofounder of Geneyx and currently serves as a scientific adviser to the company.
"The problem of genetic data that is coming out of sequencing in hospitals and labs is a huge problem," Itzhaky said. "We said, 'We are going to solve the problem about managing, analyzing, and reporting about genetic data.'"
Complicating matters, Geneyx was looking to do business in Europe, and the EU's General Data Protection Regulation (GDPR) had just taken effect.
The company had a major client in Vatican City, the Bambino Gesù Hospital, that was subject to GDPR, and has since added other European customers. The European regulation requires personal data and medical data to be stored separately, and there is some question about where DNA fits within those parameters.
Geneyx chose to segregate personal identifiers from the actual sequencing data in secure cloud environments to meet the GDPR. The firm also does business in China, where data control is essentially a matter of national security, and thus has a local host there.
Itzhaky said that Geneyx has about 130 paying customers, primarily in Europe, the Middle East, and Asia, with a few clients in the US, including Stanford University. The company largely relies on an extensive network of country-specific and regional distributors. It considers technology partners like PacBio and Oxford Nanopore to be sales channels, as well.
The company has a contract with Mediclinic Middle East in the United Arab Emirates, something that would have been impossible just a few years ago before a thawing of relations between Israel and several Arab nations. Still, Hadassah Medical Center, the firm's first customer, remains the largest user, according to Itzhaky.
Geneyx, which is based in Herzliya, Israel, with a small Foster City, California, office, raised $6.5 million in a seed funding round in 2021. The firm has not announced any other investments since the seed round, but has received some grants from the Israeli Innovation Authority and other sources.
Itzhaky said that the privately held company is close to profitability, but not quite there.
Geneyx acquired Toldot Genetics — another Israeli startup — in 2020 from bioinformatics firm BATM Advanced Communications and several minority shareholders, who in return received a 5 percent equity stake in Geneyx.
Since the Toldot acquisition, Geneyx has mostly focused on integrating and further developing the former's NGS sequencing analysis technology, then called TGex. Before and since then, the Geneyx system has provided AI-based processing, with help from LifeMap Sciences' GeneCards knowledgebase.
Geneyx had been part of a public-private consortium in Israel that collected samples and sequenced genomes from thousands of COVID-19 patients in 2020 in an effort to identify protective and risk-bearing genetic factors with the hopes of discovering new diagnostic and treatment methods for the then-novel disease. The association only lasted a few months.
"Everybody was so consumed with COVID-19, so we felt like we had to look into it," Itzhaky recalled. "That one was not one of our big successes. We were looking for something there [but] we couldn't find anything that was significant at that time."
Mor Shaked said that multiomics is "the future" for Geneyx and for genetics in general, and the company is particularly interested in combined DNA-RNA analysis. The firm already has a partnership with Ocean Genomics to bid on an R&D grant from the Israel-United States Binational Industrial Research and Development (BIRD) Foundation.
Ocean and Geneyx are seeking an unspecified amount of funding to support development of DNA-RNA multiomic software to improve the accuracy and interpretation of structural variant calling in an effort to boost diagnostic yield and identify novel drug targets, according to Itzhaky.