Elliott Swanson (lefty) and BBI's Andrew Stergachis: 'The power of new technologies is their abilities to accelerate discovery through a broad range of studies and research groups.'
Elliott Swanson, a Ph.D. student in lab of BBI’s Andrew Stergachis, M.D., Ph.D., co-led the development of DAF-seq, a single-cell, single-molecule approach that resolved how genetic variants shape genome function inside individual cells.
But Swanson didn’t take the usual path into academic research.
Raised on Bainbridge Island and the first in his family to pursue a graduate degree, he earned a Bachelor’s Degree in Cellular and Molecular Biology at Western Washington University before spending more than five years building single-cell assays in industry and at the Allen Institute. There, he designed next-generation sequencing methods that profiled chromatin accessibility, protein levels, and RNA expression, work that forged his dual fluency in wet-lab engineering and computation.
“My time at Allen gave me the freedom to ask big questions and the mentorship to pursue them,” Swanson said. “It showed me how enjoyable and creative science can be.”
That mixed training now powers Swanson’s graduate work, where he set out to overcome a central limitation in epigenomics: Most single-cell chromatin assays are sparse and fragmented.
“My experiences prior to graduate school taught me both the power and the constraints of our toolkit,” he noted. “We could only see glimmers of where proteins bind in a cell, rather than the whole picture.”
To address this, Swanson co-invented DAF-seq (Deaminase-Assisted single-molecule chromatin Fiber sequencing) with Drs. Stergachis and Yizi Mao, a former post-doctoral scholar at the UW and now at the University of California, Berkeley.
DAF-seq is a technology that synchronously reads DNA sequence and high-resolution protein footprints from the same molecules. In its single-cell form, DAF-seq resolves protein occupancy across approximately 99 percent of a cell’s mappable genome, a million-fold improvement over current state-of-the-art approaches.
A manuscript describing these advances was published December 3 in Nature Biotechnology. The study demonstrates how DAF-seq links individual sequence changes to altered protein occupancy and reveals pervasive plasticity in how each cell organizes its genome. This offers textbook insights that recalibrate how we model gene regulation at single-cell resolution.
Swanson’s translational mindset shows up elsewhere, too. He helped lead the lab’s contribution to a 2024 Nature Genetics study explaining how a non-coding variant causes the Mendelian condition Resistance to Thyrotropin (RTSH), providing answers for affected families and illustrating how advanced chromatin profiling can inform clinical genetics.
Colleagues describe Swanson as a rapid learner and generous collaborator.
“As a graduate student, Elliott has taken on bold technology-building projects to study genome function,” Stergachis said. “He’s not only delivered technically, but he’s also translated those advances to illuminate the genetic basis of rare disease.”
Looking ahead, Swanson aims to deploy DAF-seq and related long-read epigenomic tools to decipher how genomic and epigenomic alterations shape human development and disease.
“It’s an extremely exciting time in which we can leverage DAF-seq to open new avenues of research, including addressing questions that researchers have been effectively blocked from studying due to technological limitations,” he said. “The interest from the scientific community has been fantastic and has inspired powerful research collaborations.”
Swanson says that the varied applications of DAF-seq exemplify his interest in genomic technologies.
“The power of new technologies is their abilities to accelerate discovery through a broad range of studies and research groups,” he said. “This work has provided me with the opportunity to meet and collaborate with numerous researchers from across the U.S. and Europe. It’s been a very rewarding experience.”
