sam patrick posted an articleStudy shows diagnostic test effective for providing conclusive genetic results see more
GREENWOOD, SC – The Greenwood Genetic Center (GGC), working with collaborators at Lawson Health Research Institute in Canada and the University of Amsterdam, published a study this month that provides clinical validation of EpiSign, a molecular genomics test that diagnoses rare, heritable neurodevelopmental conditions. GGC has been the sole US laboratory provider of this novel diagnostic test since 2019.
EpiSign analyzes changes that affect gene expression rather than the gene sequence. Researchers have found that certain genetic disorders display unique genomic patterns, or epigenetic signatures, allowing for a diagnosis through EpiSign when traditional genetic testing has been uninformative.
The laboratory testing in the US is performed at GGC while the analysis of the results is performed using machine learning at Lawson where the EpiSign Knowledge Database was developed. This database compiles information on rare genetic diseases using laboratory analyses of the epigenetic signature from patients with suspected genetic abnormalities.
The current study analyzed data from early EpiSign testing to validate the ability of the novel test to make a diagnosis. Epigenetic signatures have been identified for over 40 genetic disorders.
The analysis studied EpiSign test performance and diagnostic yield in 207 subjects from two different cohorts. A targeted group included patients with previous genetic findings that were ambiguous or inconclusive. The second screening group was those with clinical findings consistent with hereditary neurodevelopment syndromes but with no previous genetic findings.
“Of the 207 subjects tested, 57 were positive for a diagnostic episignature including 48 in the targeted cohort, and 9 in the screening cohort. Only four remained inconclusive after EpiSign analysis,” says Dr. Bekim Sadikovic, lead researcher at Lawson and Scientific and Clinical Director of the Verspeeten Clinical Genome Centre at London Health Sciences Centre (LHSC). “This gives us strong evidence for the clinical use of EpiSign, as well as the ability to provide conclusive findings in the majority of subjects tested.”
While currently there are limited treatment options associated with many of these conditions, providing a diagnosis can help physicians better predict the course of the disease, and allows for better planning and support for the patient. EpiSign is the only test in the world that has been clinically validated for epigenetic testing for these types of genetic disorders, and in the US, is only available through GGC.
“Patients with rare diseases often wait years and undergo numerous exams and tests before receiving a correct diagnosis, if one is found at all,” says Matthew Tedder, PhD, staff scientist at the Greenwood Genetic Center, who was involved in the study. “EpiSign provides an additional high-yield diagnostic tool for clinicians to include in their evaluation of patients with undiagnosed diseases, providing better medical management for patients and hope for their families.”
The study, “Clinical epigenomics: genome-wide DNA methylation analysis for the diagnosis of Mendelian disorders", is published in February’s Genetics in Medicine.
For more information about EpiSign, visit, www.ggc.org/EpiSign.
sam patrick posted an articleSouth Carolina’s $90-million research pipeline creates jobs and improves healthcare, researchers sayResearch pipeline adds jobs and improves healthcare in South Carolina see more
The $41.8 million that has flowed into Clemson University for three separate research centers could be the beginning of a larger enterprise that brings South Carolina new business, improved patient care and lower healthcare costs.
But success will hinge on how well some of the state’s largest institutions can work together, researchers said.
The funding comes from a National Institutes of Health program that is aimed at helping South Carolina, 22 other states and Puerto Rico establish Centers of Biomedical Research Excellence. Each has a specific research theme and can receive as much as $30 million distributed in three phases over 15 years. SC BioCRAFT, launched in 2009, has received two phases of funding totaling $20.3 million. Clemson officials announced Oct. 18 that SC-TRIMH received $11 million in its first phase of funding. EPIC started in 2015 with $10.5 million.
Those centers could be just the start of a continuous funding stream– a big one that transforms the South Carolina healthcare industry. Clemson officials are preparing to apply for a fourth center and have set a goal of continuously maintaining three centers. The plan would create a pipeline worth up to $90 million at any given time constantly flowing into South Carolina for biomedical research.
Clemson bioengineers lead two of the centers, SC BioCRAFT and SC-TRIMH. They said they rely on clinicians from Greenville Health System and the Medical University of South Carolina to guide their research, ensuring it remains relevant to what happens in real-world hospitals and clinics.
“Team effort is what is required,” said Naren Vyavahare, the director of SC BioCRAFT. “A lot of institutions are required for these big grants.”
One of the gems of the centers is that junior faculty members are mentored so that they can compete for their own federal funding. SC BioCRAFT is credited with mentoring 23 faculty members and generating $35 million in addition to the $20.3 million that funds the center itself. The center is also bearing fruit off campus. Research done at SC BioCRAFT has led to 16 patents, four spin-off companies and better care for patients suffering from ailments ranging from diabetes to traumatic brain injury.
The success of SC BioCRAFT could be a harbinger for the newest center, SC-TRIMH, which is led by Hai Yao, theErnest R. Norville Endowed Chair in Biomedical Engineering at Clemson.
A key part of SC-TRIMH’s mission is developing virtual human trials that would allow researchers to test new devices with computational models before trying them on humans. The idea is to close the gap between animal and human trials, allowing new devices to move from the lab to patients’ bedsides more quickly and less expensively. It’s an approach that has been used for drugs, but SC-TRIMH will be the first to try to apply it to medical devices, a step that could attract device manufacturers to the state, Yao said.
“The companies are going to come to us,” Yao said. “Why? Because we have the technology, and we have clinical partners here. So, we can test their products– not just test their products but use our technology to totally redesign their products.”
Initial research could apply to bad discs in the back, hip replacements and disorders of the temporomandibular joint, Yao said.
Martine LaBerge, chair of the Department of Bioengineering at Clemson, said SC-TRIMH could improve patient care for South Carolinians by staking a claim as a national leader in musculoskeletal health, the center’s primary focus.
“If we’re the leader, why would a patient need to fly to another state for treatment?” she asked. “We’ll become the leading health provider. Patients from other states may have to fly to South Carolina. This is our goal, and collaboration among institutions will be crucial to making it happen.”
Tanju Karanfil, vice president for research at Clemson, said officials are preparing to apply for a fourth center but will have to wait until 2020, because NIH rules limit each institution to three centers in the first two phases. He said that he is hopeful that SC BioCRAFT will receive Phase III funding.
“This is excellent for a university without a medical school,” Karanfil said. “Of course, with all credit, we are working with GHS, MUSC and USC. Their clinical expertise is indispensable.”
Vyavahare, the Hunter Endowed Chair at Clemson, took the lead in organizing the university’s first center, SC BioCRAFT, starting in 2006. The first proposal was rejected, and then a federal funding shortfall in 2008 put the program on hold for a year, he said. SC BioCRAFT received its first $10 million in 2009, and funding was renewed for the second phase five years later. Vyvahare said he is most proud of the center’s junior faculty.
SC BioCRAFT provided mentors who helped guide them through the research funding process, he said. The center also helped pay for new research equipment that is crucial to generating the data needed for a successful research proposal, Vyavahare said.
“It’s a good way to start your career quickly,” Vyavahare said. “A lot of people started getting good data, and everybody started getting funding.”
SC BioCRAFT is an acronym for the South Carolina Bioengineering Center for Regeneration and Formation of Tissues. SC-TRIMH stands for the South Carolina Center for Translational Research Improving Musculoskeletal Health. EPIC stands for Eukaryotic Pathogens Innovation Center.
Researchers said one of the key ingredients in the success of SC BioCRAFT and SC-TRIMH is Clemson’s deep integration with GHS and MUSC.
Both centers are based at the Clemson University Biomedical Engineering Innovation Campus, or CUBEInC, which is on the GHS Patewood Medical Campus in Greenville. Research is also conducted at MUSC, where Clemson has space in the medical university’s Bioengineering Building.
The value of collaboration was a consistent theme when researchers from the three institutions gathered to announce the creation of SC-TRIMH.
Scott Sasser, chief clinical officer for the GHS western region, said that Clemson was the health system’s primary research partner.
“That was by design, and it is unique,” he said. “We are so thankful for your investment in the medical school. The successful medical education of every student who walks through our doors is inextricably tied to your commitment to research that this project exemplifies.
“The novel methodology that will be used in this program will lead to new innovations and new devices that will not only change health outcomes but will help us all address the rising cost of healthcare in this country.”
Michael Kern, a professor in the Department of Regenerative Medicine and Cell Biology at MUSC, said what excites him most about SC-TRIMH is the chance to continue working with Yao.
“My research and Hai’s research before the COBRE grant have dovetailed nicely,” he said, using the acronym for the NIH funding program. “We’ve worked quite closely together for the previous 12 years. With the COBRE, we will be able to continue our work together to benefit young investigators and help them mature in their science.”
Kathleen Brady, associate provost for clinical and translational science at MUSC, said collaboration is part of a growing trend in research because it leads to success.
“When groups get together, studying a similar problem, you’re much more likely to come up with innovative solutions,” she said. “They are usually innovative solutions that neither group could have come up with on their own. SC-TRIMH is a perfect example of that– people with very different expertise coming together to do something unique and innovative.”
Spence Taylor, president of GHS, said in a written statement that working together can lead to significantly improved health care and health outcomes in South Carolina and the nation.
“These innovative partnerships between Clemson faculty and GHS clinicians allow us to solve clinical challenges by leveraging medical insights with the extraordinary research depth of Clemson,” he said. “What we do today can pave the way for transformational improvements to health care for generations to come.”
Vincent Pellegrini, chair of the Department of Orthopedics at MUSC, said much of the SC-TRIMH research will focus on musculoskeletal conditions that result from normal aging, including arthritis at the base of the thumb, hip replacement prostheses and tendon degeneration.
“The really exciting thing about the COBRE is that it juxtaposes the engineering, science and clinical medicine with the appropriate individuals in those disciplines on the same campus under the same roof to come up with real, clinically relevant devices and products that benefit patients,” he said.
Michael Kissenberth, a GHS orthopedic surgeon, said the collaboration will allow the institutions to complement each other
“We at GHS will be able to advise on the clinical needs that Clemson can then use to develop the technology that improves health outcomes,” he said. “In some cases, the technology may exist, and we can help show how it can be applied.”
Kyle Jeray, a GHS orthopedic surgeon, said SC-TRIMH will strengthen the collaborative spirit in South Carolina’s research community.
“Through SC-TRIMH, we will enhance the research infrastructure at Clemson and GHS by developing essential core facilities, fostering research collaborations and increasing scientific expertise of junior and senior faculty members,” he said.
Windsor Sherrill, associate vice president for Health Research at Clemson and chief science officer at GHS, said she wanted to recognize Tommy Gallien, the manager/coordinator for SC-TRIMH. She also wanted to acknowledge the Clemson University School of Health Research, or CUSHR.
“CUSHR is the interdisciplinary health research entity at Clemson that connects health researchers across colleges and departments with clinical researchers at health care systems such as GHS and MUSC,” she said. “The junior investigators for the SC-TRIMH initiative are from several different departments, ensuring that we have multidisciplinary focus to solve complex health care problems. The big challenges in health care do not fit neatly within one discipline or even in one university. SC-TRIMH is the kind of program we envision with CUSHR– one that leverages talents across Clemson health research faculty with the input of clinicians research at our partner institutions.”
Anand Gramopadhye, dean of the College of Engineering, Computing and Applied Sciences, congratulated Yao and his team on the SC-TRIMH grant.
“Through this grant, Dr. Yao and his team from Clemson, GHS and MUSC are strengthening the biomedical research capacity for South Carolina,” he said. “The award is a testament to the scholarship that Dr. Yao brings to Clemson and the power of collaboration to achieve the most innovative results.”