Photo caption: January’s record-breaking storm dropped a foot of snow in Pittsburgh, blocking roads and halting genomic sample transport.
By Phoebe Ingraham Renda
Photography by Aimee Obidzinski, University of Pittsburgh
While most of Pittsburgh was snowed in after a record-breaking storm at the end of January, the University of Pittsburgh’s High Throughput Genomics Core (HTGC), was focused on setting its own record after receiving an urgent call.
UPMC Children’s Hospital of Pittsburgh providers called late in the afternoon on Jan. 29 requesting ultrarapid whole‑genome sequencing (WGS) for two neonatal intensive care unit patients with pressing clinical needs. A foot of snow and brutal cold left many roads blocked, stalling the courier services that would typically send the samples to an external lab.
Faced with the urgency of caring for its tiny patients, the provider from Children’s contacted Fen Guo, scientific director and CLIA/CAP director of the UPMC Clinical Genomics Laboratory (UCGL) and the University of Pittsburgh’s HTGC. The request arrived just 19 business days after UCGL launched their standard clinical WGS test through HTGC and UCGL’s partnered distributive model, which enables UPMC physicians to order in-house genetic tests directly through patients’ electronic health record, with a six‑week turnaround. However, the partnership’s rapid‑turnaround workflow was still under development.
Following the call, Guo and leadership from HTGC, UPMC Magee-Womens Hospital, UPMC Lab Services and Children’s quickly convened and, on Jan. 30, agreed to mobilize internal resources to perform the rapid clinical testing in‑house and over the weekend. HTGC’s laboratory manager, Lindsey Kelly, volunteered her time. That same day, Kelsey Bohnert, of Children's lab services, drove the samples from Children’s to UCGL at Magee, as the internal courier service UCGL uses for samples was also out of service because of the severe weather.
The HTGC and UCGL teams were able to generate diagnostic-grade results in less than four days—significantly less than a typical five to seven business day rapid request timeline.
“This definitely created a milestone for us,” says Guo, who is also an assistant professor in Pitt’s Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine. “Not only did we just launch the whole genome sequencing service using this distributive model, but also just in the short term, we were able to deliver the results within four days.”
Getting the results back quickly helped provide a timely diagnosis that directly affected the plan of care for one of the patients, as the sequencing result revealed a known genetic variant that causes ornithine transcarbamylase deficiency.
“We are deeply grateful for everyone’s dedication, flexibility and teamwork in completing our first rapid-WGS cases—although not initially planned—and demonstrating our collective ability to rise to urgent clinical needs in the best interest of our patient care,” says Guo.
The University’s investment in HTGC’s Clinical Laboratory Improvement Amendments/College of American Pathologists (CLIA/CAP)‑certified large-scale sequencing infrastructure, together with the dedication of faculty and staff across HTGC and UCGL, not only served as a pilot of their rapid sequencing workflow under real-world conditions, but set a benchmark for the collective in‑house clinical genomic sequencing capabilities available through the HTGC-UCGL partnership to support UPMC patients of all ages and clinical needs.
Although the second patient’s genomic results did not identify any known pathogenic variants to immediately guide their care—a common outcome in genetic testing—HTGC is addressing the challenge. Guo notes that HTGC will serve as a clinical translational incubation hub by working collaboratively with clinical partners, clinician‑researchers and investigators through established multiomics platforms to accelerate the validation process for “variants of unknown clinical significance” and uncover additional genetic etiologies in unresolved cases. This effort will streamline the diagnostic process, generate translational clinical evidence and inform emerging therapies for patients and others who share the same genetic variants.
Together, the partnership between HTGC and UCGL reaffirms Pitt’s standing as a leader in genomic and multiomics innovation and as a driving force behind scalable clinical sequencing infrastructure. It also illustrates HTGC’s role in accelerating the cycle of discovery—from bench to bedside and back again—to expedite translation into clinical practice.