After much of Los Angeles went dark in the spring of 2020 amid the growing SARS-CoV-2 threat, two UCLA scientists and their small team began working late nights on the fifth floor of the Gonda (Goldschmied) Neuroscience and Genetics Research Center, developing technology that would pave the way for the UCLA community to safely return to campus.
The safer-at-home orders had shut down all but the few core campus activities and services deemed essential. While that meant the suspension of most laboratory research, it didn’t apply to a new project led by Valerie Arboleda M.D. ’14, Ph.D. ’14, assistant professor of pathology and human genetics, and Joshua Bloom ’06, a research scientist in human genetics and an adjunct professor in computational biology. Through their collaboration with Octant Bio, a biotech company founded and incubated at UCLA; faculty in UCLA’s departments of human genetics and computational medicine; UCLA Health; and other academic institutions across the country, their research ultimately found its way from the high-tech lab Arboleda and Bloom named SwabSeq to vending machines across campus. UCLA faculty, staff and students returning last fall were able to easily access the free COVID-19 test kits, with picking up a test as simple as grabbing a snack: Users simply register for the SwabSeq test by scanning a QR code with their smartphone, retrieve the kit and collect their saliva sample, then deposit the kit in a drop box next to the machine. An email or text notifies them when they can access a secure website for their result.
Diagnosing COVID-19 typically involves polymerase chain reaction (PCR) testing, but as a tool for mass screening of asymptomatic individuals, the approach is limited in its capacity. To run tens of thousands of tests simultaneously, SwabSeq harnesses the power of next-generation DNA sequencing — a revolutionary technology that’s come of age in the last 15 years and enables the processing of millions of DNA fragments at a time. The testing platform also bypasses a step typically required in the PCR method — that of extracting RNA from samples, which can take days to process.
“I’m thrilled that SwabSeq helped put us back on campus and that my students and I are able to come into the lab.”
— Valerie Arboleda
SwabSeq attaches a piece of DNA that acts like a molecular barcode to each person’s sample, enabling the lab’s scientists to combine large batches of samples in a genomic sequencing machine. Viewing the “barcodes” in the resulting sequence, the technology can quickly identify the samples that have the coronavirus that causes COVID-19. SwabSeq can return individual test results in about 24 hours, with highly accurate results — the false-positive rate is just 0.2%.
SwabSeq has now tested more than half a million specimens from UCLA, as well as from a handful of other universities in Southern California and from the Los Angeles Unified School District. A $13.3 million contract recently awarded by the National Institutes of Health sets the stage for an expansion of SwabSeq’s efforts.
“This is an innovative use of genomic sequencing for COVID-19 testing that is uniquely scalable to thousands of samples per day, [and that is] sensitive and fast — a combination that is challenging to find in diagnostic testing,” Arboleda says. “It’s not cost-effective as a test for a few people, or if you have someone in the hospital who needs an immediate result, but it’s very effective as a screening tool for large asymptomatic populations.”
Neither Arboleda nor Bloom could have predicted they would one day find themselves leading a major element of UCLA’s research response to a once-in-a-century pandemic.
Arboleda entered the David Geffen School of Medicine at UCLA intending to become a full-time clinician, but when she took a year off from her medical school studies to work in a lab, she found her true calling. She enrolled in the UCLA Medical Student Training Program, graduating in 2014 with both an M.D. and a Ph.D. in human genetics. As a faculty member, she now devotes about 80% of her time to research, with much of the focus on rare genetic syndromes.
Bloom, trained as a geneticist and a computational biologist, has used model systems such as yeast to develop experimental and computational methods for identifying the heritable genetic factors underlying gene expression differences and other complex traits in large populations. “I’ve worked on some really abstract problems. Diagnostic testing in a pandemic is definitely not something I thought I’d ever be involved in,” he says, smiling.
Like most of their UCLA colleagues and much of the rest of the world, Bloom and Arboleda saw their work routines upended by the pandemic. Bloom was grappling with the new reality when he received a call from Sri Kosuri, a UCLA assistant professor of chemistry and biochemistry and co-founder/CEO of Emeryville, California-based Octant Bio, the startup where Bloom was a consultant and where early pilot studies for SwabSeq were conducted.
“He suggested we could turn the drug-screening technology Octant was using into a COVID test, and asked if I could help with the computational work,” Bloom recalls. “There were other people at UCLA who were also thinking that with all these smart people here, we should be able to develop a test. From there we began to have large group meetings involving multiple universities sharing information.”
When Arboleda heard about the nascent project from a faculty colleague, she knew she could be helpful. In addition to the expertise in molecular biology she could apply to setting up the experiments, her training in pathology gave her the experience with regulatory matters that would need to be addressed once the test was developed. She agreed to collaborate with Bloom, who used his expertise in informatics to optimize the automated DNA sequencing process toward the goal of producing accurate diagnostic readouts.
The two spent a good part of April and May 2020 in the lab. “We would do the assay and put it on the sequencer, then Josh would analyze it as soon as it came off the machine,” Arboleda says. “Based on that, the next day we would adjust a couple of parameters and rerun the experiment.”
Pre–COVID-19, she had become accustomed to a supervisory role as a principal investigator overseeing a team of scientists. “I hadn’t gone back to the lab in a while,” she says. “It was a wild two months, where I felt like a grad student again!”
The number and pace of the iteration cycles — a new one every 24 hours — made this research project unlike any other Bloom had seen. “The sequencing technology enables that, because you can tweak a bunch of things and get readouts for them all at once,” he says.
But more than that, he credits the speed with which SwabSeq moved from concept to reality to an all-hands-on-deck approach befitting the urgency of the need. “We had senior faculty, including department heads, engaged and excited to help,” Bloom says.
One of those department heads is Eleazar Eskin, chair of the Department of Computational Medicine, a department affiliated with both UCLA Samueli School of Engineering and the medical school. He has coordinated logistics and business operations to ensure that the lab operates efficiently and remains flexible enough to adapt to changing circumstances, such as the appearance of the omicron variant of the virus. Eskin also built the custom software for SwabSeq's lab-information management system.
Adds Arboleda: “Everyone knew it was important and contributed in whatever way would support the mission, whether it was getting space, funding or institutional review board approvals. And since only people who were doing COVID work could come to campus, I had people on my team who said, ‘OK, I’ll put on a mask and do what’s needed.’”
The SwabSeq lab now occupies an entire floor in the Center for Health Sciences South Tower. The space is divided into three rooms, each dedicated to a portion of the test. One room is for handling samples; a second is used as a clean room and storage area; and a third, its walls lined with high-level sequencers, is for post-PCR sequencing. All over, freezers and refrigerators store enough reagents for millions of tests. The lab isn’t necessarily a one-off — Arboleda notes that the technology can be applied to general infectious disease testing and surveillance. “Its flexible protocol can rapidly scale up testing and provide a solution to the need for population-wide testing to stem future pandemics,” she says.
For now, aside from regular meetings to discuss SwabSeq development and high-level technical issues, the scientists have returned to the work they were doing before everything changed in March 2020. “I’m thrilled that SwabSeq helped put us back on campus and that my students and I are able to come into the lab,” Arboleda says. “Now if someone tests positive, no one worries because that person can stay home, and we know we can all easily get tested.”