NEW YORK – An international consortium of researchers has put together a framework for the clinical implementation of optical genome mapping (OGM) for hematologic malignancies.
Published in the American Journal of Hematology earlier this month, the document outlines recommended practices for incorporating OGM-based assays for the analysis of structural variants in patients, setting the stage for the wide and uniform adoption of the technology in hospitals across the globe.
"When we started developing the technology in the laboratory … we started finding that we had lots of questions right from the beginning," said Adam Smith, a researcher at the University of Toronto and the framework’s corresponding author. "One of the things we really wanted to do early on was to provide this framework to people, so we could get harmonization about how the test was implemented and reported across the globe."
The framework was published by several researchers who are early adopters of OGM. The group, named the International Consortium for Optical Genome Mapping in Hematologic Malignancies, was formed in late 2021 as a forum to exchange knowledge and experience for adopting OGM clinically, Smith said. It includes 17 founding members, representing 11 institutions from seven countries.
According to Smith, the framework reflects the collective experience of all the institutions within the consortium and focuses particularly on myeloid diseases. It delineates three components that are critical to the successful clinical implementation of OGM: validation, quality control, and analysis and interpretation.
"We tried to lay out a roadmap that if you want to validate [your OGM] assay, these are the considerations that you need to think about," Smith noted. The document, however, is not an official guideline by a professional organization, he stressed.
"New technologies come out, and it takes a long time for the professional societies to release guidelines," Smith said. "That means there's a huge amount of time where lots of people struggle to implement [it], so what we wanted to do is to short-circuit that pathway."
"What I like about this paper is that it is a very practical guide, sharing from these early adopters with a much broader community," said Alexander Hoischen, a genomics researcher at Radboud University Medical Center in the Netherlands and a coauthor of the framework. "If people start with OGM today, they can read this paper to have a smooth kick-start for the clinical applications."
According to Hoischen, whose team was one of the first OGM users in Europe, Radboud UMC is "on the verge of pushing final clinical implementation" of the OGM test. The assay will first be used for acute myeloid leukemia (AML) patients, he said, with the eventual goal to apply it in other types of leukemia and to replace current standard-of-care assays, such as karyotyping, fluorescence in situ hybridization (FISH), and microarrays.
In addition to the consortium's framework, the clinical adoption of OGM is also bolstered by another paper published in Cytogenetic and Genome Research earlier this month, which outlines the addition of genome mapping to the International System for Human Cytogenomic Nomenclature (ISCN), an international standard for describing genomic rearrangements.
"If you look back at all of the publications until now, each paper has used a different terminology or nomenclature for reporting OGM abnormalities," said Rashmi Kanagal-Shamanna, a molecular genetic pathologist at MD Anderson Cancer Center who coauthored the nomenclature paper. "It is very timely that the [genome mapping nomenclature] was released at this time when the OGM is getting adopted into clinical labs."
"It also goes to show that if the ISCN is ready to incorporate [genome mapping] in its nomenclature guidelines, it means [the technology] is ready for patient care," she added. In addition to being part of the ISCN standing committee, Kanagal-Shamanna also belongs to the International Consortium for OGM in Hematologic Malignancies and is a coauthor of their framework paper.
According to Kanagal-Shamanna, MD Anderson’s cytogenetics laboratory has already developed OGM into a clinical test for leukemia patients. The hospital currently has trained four faculty to help interpret the assays and report the results into clinical charts.
Still, throughput can be a limitation for the wide clinical implementation of OGM technology, Kanagal-Shamanna noted. As such, the hospital is currently offering the assay to 15 selected patients weekly. "It would be nice to increase the throughput," she said. "Our hope is that we are able to expand the test and offer it to every new patient."
Moreover, she said, MD Anderson is working to seek insurance coverage for the OGM test, which can be "extremely critical" for the technology’s clinical adoption. "Even though OGM is not as expensive as next-generation sequencing and it offers a lot of value clinically, the insurance information is absolutely important for patients and oncologists to be willing to integrate it into the standard-of-care workflow," she noted.
In that regard, the laboratory services subsidiary of Bionano Genomics, the maker of the OGM platform, is "actively in pursuit" of local coverage determinations (LCDs) through its Medicare administrative contractor, said CEO Erik Holmlin.
In addition, two clinical labs, one at Augusta University and Praxis Genomics, have already secured reimbursement codes for their OGM assays, receiving about $1,850 per test, he said.
Commenting on the framework, Holmlin said he considers the paper "really significant" for the OGM community, and in turn for the company commercially. "We are aware that a lot of labs are seeking to adopt OGM and use it for clinical applications," he said. "Given that the Saphyr system and our products are for research use only, we have some limits as to how far we can go to support labs."
To address the throughput limitation of the current Saphyr system, Holmlin said, the company has been developing and is about to launch its new Stratys platform, which promises to deliver four times the throughput. Bionano in 2023 built about 10 Stratys platforms, which are being evaluated by customers through an early access program, he said, adding that the company plans to make more Stratys systems available early this year.
However, Bionano is unlikely to move forward in the genome mapping field without competition. Providence, Rhode Island-based Nabsys, for instance, has been developing its electronic genome mapping technology, with investments from Hitachi High-Technologies in recent years after its previous bankruptcy.
Nabsys showcased its platform, named OhmX Analyzer and recently commercially launched, at the American Society of Human Genetics (ASHG) annual meeting last year.
"We are interested in structural variation at the genome level, so we get very excited about all of those technologies," said Smith. While he has not used the electronic genome mapping technology personally, he believes the structure of the OGM framework would potentially be applicable across multiple technologies.
"Our ultimate goal is structural variant analysis and cytogenomic analysis regardless of the technology," said Kanagal-Shamanna, who also stressed that she has not tried out the electronic genome mapping technology. "I think the majority of the framework would be similar." Still, she said she does not think the other genome mapping technologies "are yet there."
Moving forward, the consortium plans to include more members, she said, and to establish specific working groups to address disease-specific questions collaboratively.
To that end, Kanagal-Shamanna and other consortium members are currently working on another manuscript to provide guidelines on how OGM fits within current standard-of-care cytogenetic techniques, such as FISH, microarrays, and NGS mutation analysis.
"You cannot expect people to get rid of the standard workflow and replace it with OGM, but at the same time, there are certain diseases or a subset of diseases where OGM plays a way more important role compared to cytogenetics," Kanagal-Shamanna said. "We are coming up with guidelines recommending where exactly OGM fits into the current workflow."