10,000 Genomes Sequenced, and Counting

Summer 2020
A decade ago, if you were a university researcher or a clinician who wanted to sequence some RNA or a full genome, your week might have looked like this: Send out a sample to an off-site, private company, pay them a stack of money, wait for them to sequence it and hope that your sequencing quality wasn’t a total dud. “You just dealt with it,” says Udai Kammula, director of the Solid Tumor Cell Therapy Program at the UPMC Hillman Cancer Center and associate professor of surgery at the University of Pittsburgh. Now, as Kammula studies RNA and full genome sequences of cancer cells, he does it all at home base, for much less and with a quicker turnaround time.
Since November 2018, researchers and clinicians alike have sent their to-be-sequenced samples to UPMC’s own Genome Center. Five behemoth next-generation sequencers, which look more or less like photocopiers, as well as a series of robotic arms have sequenced more than 10,000 samples since the center opened, says Annerose Berndt, director of the Genome Center and faculty member in medicine.
Berndt says that beyond scale, however, the unique part of the Genome Center is that it’s embedded within an academic medical center. “It’s very valuable to have both the research side and clinical side under one roof,” says Berndt. 
So, what does this mean for research and for patient care?
For instance—how the capability might be applied in the lab:
Cameras have a feature built in called “white balance,” in which the camera can look at a white wall during the golden hour or during a dim, blue dusk and say, “That, right there, is not golden or blue—that’s what white looks like.” It knows what normal white looks like, so it’s able to correct itself if it sees off-white.
Kammula is trying to do the same sort of thing at the Genome Center. If he and his colleagues can sequence some normal RNA, say, from bone marrow, then compare it against RNA in a patient’s mutated tumor cell, then they will be able to identify all the abnormalities for that particular patient. They’ll be able to see the off-white.
For instance—how it’s showing up in the clinic:
As clinicians in the NICU attempt to diagnose an infant’s condition, they may spend lots of time iterating through a series of diagnostic tests, says Adrian Lee, director of Pitt’s Institute for Precision Medicine and professor of pharmacology and chemical biology. “If they’re wrong, they go back and try to figure it out again and order another test; and if that goes wrong, they order another test,” says Lee. This kind of reactive testing, what’s known as a diagnostic odyssey, has been the standard of care for years.
With the capabilities of the Genome Center, however, UPMC’s NICUs are turning toward a single genomic test. They are evaluating a new test for children in the NICU, says Lee. 
“If you do whole genome sequencing up front, oftentimes you can immediately know the diagnosis, and sometimes that changes medical care.” 

In The Classroom

Philip Empey, associate professor of pharmacy and therapeutics, was teaching a pharmacogenetics class in 2014 when he had the idea for a class project: Would students be interested in going through genetic testing personally and using the resulting data in class exercises? With a resounding “yes” from students, thus began his Test2Learn curriculum. A program based on Empey’s model has received funding from a $2.8 million grant from the Richard King Mellon Foundation to integrate with the UPMC Genome Center. The grant will equip learners with the Genome Center’s ability to do full genome sequencing.
The expanded program will teach practicing providers about applying genetics to care. Mylynda Massart, an assistant professor of family medicine at Pitt who helped write the grant proposal, says the program builds excitement about a topic people may have found unengaging previously.
“Not everyone is as excited about genetics as we are,” says Massart. The “secret sauce” in their program, she says, is that “clinicians have the opportunity to learn about genetics using their own DNA. Simultaneously, there’s a drive to better understand and better integrate the knowledge.” And, she notes, that firsthand experience helps them care for their patients.  
Photo: University of Pittsburgh Genome Center
Photo Illustration: Elena Cerri