Patient Care

URMC Pilots Optical Genome Mapping for Patient Care

Sep. 30, 2021
Cutting-Edge Technology Could be the New ‘Gold Standard’ for Chromosomal Diagnostics
Optical Genome Mapping
M. Anwar Iqbal, Ph.D., FFACMG left, professor and director of the DNA Microarray Lab and principal investigator of URMC-Bionano clinical study project on optical genome mapping, and Bin Zhang, Ph.D., FACMG, associate professor and director of the Cytogenetics Lab, stands with the Saphyr OGM instrument, which URMC is helping to pilot.

Every decade or so, a new technology comes along to help clinical labs identify genetic abnormalities. This has an immediate impact on patients awaiting potentially life-changing information in their lab report. Whether the patient is a pregnant mother, a young child, someone with rare cancer or genetic disease, lab results are the first step in reaching an accurate diagnosis and targeted therapy. 

To help advance care, the DNA Microarray Laboratory within the Department of Pathology & Laboratory Medicine is participating in a new multi-institutional study aimed at validating an up-and-coming genomic technology, with the goal of getting it one step closer to clinical application.

M. Anwar Iqbal, Ph.D., FFACMG, professor and director of the DNA Microarray Lab at URMC, is the principal investigator of the study agreement titled “Clinical research evaluation of optical genome mapping (OGM) technology for the identification of constitutional and somatic genomic variants” using the Saphyr® instrument developed by the San Diego-based Bionano Genomics.

About the Study

The Saphyr instrument has not yet been cleared by FDA for use in clinical labs, and is sold for research use only, so a primary goal of this study is to collect supporting data from participating institutions that demonstrates its utility and effectiveness. In return, URMC has a valuable opportunity to get its feet wet with the most cutting-edge technology and provide helpful insight to the developers as they look to bring it to diagnostic labs.

URMC’s microarray lab is now running hundreds of (previously tested and de-identified) abnormal patient samples on Saphyr. The data will then be compared to those yielded by traditional methods: DNA microarray, FISH, and karyotyping.

Iqbal explained that each of these methods has its own strengths and weaknesses for a variety of reasons. In simple terms, there are certain abnormalities that can be detected by one method but may go undetected by another, so it’s common to test the same patient sample with more than one method.

Hopefully, future developments in genomics may provide a single platform for all types of tests. The benefit of OGM, experts say, is that it combines the best of all three into one by scanning the entire genome to flag and report any and all possible abnormalities. Iqbal expects the existing testing methods to continue to stick around but is enthusiastic about the possibilities OGM presents, especially for our institution.

“URMC has always wanted to be at the forefront of the most state-of-the-art technology, and received the full support from URMC to pursue OGM,” he said.

Though OGM is not yet validated by New York State, a parallel in-house validation study is also being done to bring it one step closer to clinical testing. “We are taking the initiative to show that it can be robust and powerful to use for patient care.”

Iqbal’s lab is one of the clinical research multi-institutional sites for prenatal, postnatal and leukemia/lymphoma studies across the U.S.

Optical Genome Mapping Lab
DNA Microarray Lab Supervisor, Mary Shaver, and Laboratory Technician, Kamel Awayda, observe and analyze Saphyr data plotted on a genome map – a detailed visual report of DNA results that identifies genetic abnormalities on a molecular scale depicted as Circos Plot.

How it Works

Using this innovative technology begins with the isolation of ultra large fragments of DNA from patient samples. To visualize the DNA, a chemical label which fluoresces green is added to specific sites across the length of it. The labeled DNA is then put through nanochannels on a specially designed chip which runs each DNA molecule. 

A high resolution camera paired with a microscope allows for precise optical mapping of the DNA molecules to a reference genome. This process produces a genome “map” with all chromosomal structural variations (SVs) compared to the reference genome. Most of these variations are benign, but the few which are pathologically significant are the main cause of genetic abnormalities.

What makes OGM unique is its ability to detect all classes of SVs with unprecedented resolution and accuracy, from hundreds to millions of individual DNA basepairs, which are the building blocks of the genome. From a staffing perspective, this manual process requires precision, from the DNA extraction and labeling to loading and running samples on the Saphyr instrument.

The URMC team of DNA microarray technologists have hit the ground running with Saphyr since they started using it in June. Microarray Lab Supervisor, Mary Shaver, said that while there has been a slight learning curve to using OGM, it has invigorated her team to know they are making a difference in patient care.

“It is very hands-on,” said Shaver, who said that getting to see whole strands of DNA is remarkable in itself. “I really believe it might be a game changer for cytogenetic diagnostics.”