Children’s Mercy Hospital in Kansas City has achieved a breakthrough in pediatric genomics by developing a process for conducting whole-genome sequencing tests within clinical settings. Dr. Tomi Pastinen, director of its Genomic Medicine Center, reveals that the next step is to employ this genomic data in clinical validation testing. The hospital has also become the first to offer genetic testing at the patient’s bedside. This advancement is driven by the decreasing cost of genetic testing, making it a standard in various medical specialties. Genomic data is securely stored, while deidentified genetic variant data is shared through NIH resources for research and diagnostic purposes.
Children’s Mercy Hospital in Kansas City has made significant strides in advancing pediatric genomics. The hospital has developed a groundbreaking process for conducting whole-genome sequencing tests within a clinical setting. Dr. Tomi Pastinen, the director of its Genomic Medicine Center, emphasizes that the next crucial step is to utilize this valuable genomic data in clinical validation testing.
To address pediatric diseases, Children’s Mercy Kansas City has been actively performing whole-genome sequencing tests. In a recent development, the hospital proudly announced its pioneering role as the first healthcare organization to bring genetic testing directly to the patient’s bedside, as stated by Dr. Tomi Pastinen, the director of the Center for Pediatric Genomic Medicine.
Meanwhile, the cost associated with genetic and genomic testing has been steadily decreasing, making it an integral part of standard care for conditions such as cancer and neonatal care. During the COVID-19 pandemic, healthcare institutions began exploring the potential of genetics to support various medical specialties, including tailoring therapy with pharmacogenetic insights for elderly chronic care patients, according to Joel Diamond, the cofounder and chief medical officer of 2bPrecise.
Notably, the costs of genetic tests are now lower than lipid profiles and consumer ancestry tests. Furthermore, a single genetic test can provide lifelong value to a patient. This advancement in precision medicine allows clinicians to gain a deeper understanding of the molecular drivers behind diseases, ultimately leading to improved patient care, as elaborated by Dr. Pastinen in an exclusive Q&A session.
Q. Could you explain how clinical whole-genome sequencing testing in a clinical setting functions?
A. While we currently employ HiFi sequencing in the clinical setting, our journey began in late 2020, pioneering advancements in the human genome using HiFi-GS and 5-base HiFi-GS. These innovations have revolutionized the diagnosis and understanding of unsolved pediatric diseases.
The introduction of five-base HiFi-GS marked the first time researchers could both sequence the entire genome with exceptional accuracy and measure methylome, enabling us to interpret genome function and identify disease variations never before seen in a single test. Over the past two and a half years, we have successfully sequenced over 1,500 human genomes, primarily from patients who participated in our research efforts to uncover genetic diagnoses that were beyond the capabilities of conventional clinical sequencing. We have successfully resolved numerous cases where previous clinical testing had fallen short. Notable successes include identifying repeat expansion diseases and disease variants where the detection of DNA methylation patterns played a critical role in the diagnostic process.
Q. How does this testing expedite the search for novel treatments for pediatric genetic conditions?
A. Our approach represents a global milestone, as it brings advanced genomic sequencing out of the research laboratory and into clinical practice, providing answers for more patients and their families. This cutting-edge technology supplants traditional diagnostic tests like rapid exome sequencing and chromosomal microarray analysis, becoming the primary expedited assessment for critically ill patients suspected of having a genetic disease.
This testing has enabled us to consolidate multiple tests into one, significantly increasing efficiency and diagnostic yield. Moreover, we have dramatically shortened the turnaround time for test results. Whereas multiple legacy tests could take months to produce results, HiFi sequencing now delivers outcomes within two weeks.
Since this comprehensive testing encompasses many assessments in one, it ensures that even if the healthcare provider did not initially consider all possible genetic mechanisms in the primary test order, the patient’s genome data includes coverage for rarer but challenging-to-detect diseases. This approach may yield valuable information regarding the presence of diseases that previously required separate test orders.
Some of these hard-to-detect genetic variations occur in treatable conditions, and early testing for these conditions opens up new management options for this subgroup of patients.
Q. What infrastructure is necessary to offer whole-genome sequencing in a clinical setting?
A. Building a repository of genome data is a crucial prerequisite for interpreting rare and potentially diagnostic variants within genome sequences or their associated methylation patterns. The next step involves utilizing this data resource to validate known disease variations through clinical testing. To achieve this, standardized workflows in the laboratory, complete with documentation to meet regulatory requirements, are essential. Similarly, for data analysis and reporting, well-documented sequence data processing methods that have matured during our research work are indispensable.
Q. How is the data shared and protected?
A. All identifiable medical data, including linked genome-sequencing data, is stored with the utmost security, following the same protocols as any other medical data within health systems. In the context of genetic diseases and to advance the identification of patients with rare genetic variations, the clinical community shares deidentified genetic variant data through National Institutes of Health (NIH) resources like ClinVar. All such shared variations pertain solely to individual DNA variants interpreted by clinical laboratories, with all personal information fully decoupled and protected.
