Mary O'Neill, Ph.D., BBI's Director of Single Cell Genomics (left) and Research Scientist Kathryn Barker prepare samples of zebrafish cells for analysis by the Seattle Hub for Synthetic Biology. 'Generating datasets of this scale is something most scientists have never had the opportunity to do.'
BBI’s Single Cell Genomics Team is helping empower not one – but two – research projects making “transformative discoveries across precision medicine and functional genomics.”
The projects, the Seattle Hub for Synthetic Biology and the Billion Cells Project, use artificial intelligence to drive the future of how scientists and clinicians diagnose and treat illnesses.
For the head of the Single Cell Genomics Team, the work is as exciting as it is challenging.
“It’s exciting to see the scale of it all,” said Mary O’Neill, Ph.D., Director of Single Cell Genomics. “In my post-doc we used droplet-based sequencing technologies. We generated a million cell data set from more than 120 libraries. That work led to a paper published in 2023 in Nature. With the combinatorial indexing techniques we use at BBI, we can easily surpass one million in a single experiment. For these projects, we are doing this almost weekly. Generating datasets of this scale is something most scientists have never had the opportunity to do.”
As part of the Seattle Hub for Synthetic Biology and the Billion Cells Project, O’Neill and her team work closely with three BBI-affiliated labs: those of Drs. Jay Shendure, M.D., Ph.D, Cole Trapnell, M.D., Ph.D., and Nobuhiko Hamazaki, Ph.D.
The Billion Cells Project was announced in February by the Chan Zuckerberg Initiative (CZI). It is an endeavor to generate an unprecedented one billion cell dataset to “fuel rapid progress in AI model development in biology,” according to a press release. In addition to BBI, this “landmark initiative” is working with 10x Genomics, a life science technology company, and Ultima Genomics, a biotechnology firm, as well as other corporations and academic institutes.
The Seattle Hub for Synthetic Biology - a collaboration among BBI, CZI, the Allen Institute, and University of Washington - is creating cellular recording technology to capture live data from millions of cells responding to their environment within an entire organism.
“Using reverse genetics, the research goes a step further, systematically altering or perturbing genes to illuminate which genes cause which downstream changes,” according to the Allen Institute website.
BBI’s Single Cell Genomics Team is up to the challenge of collaborating with the Shendure, Trapnell, and Hamazaki labs as they contribute to the two projects. The experiments have consumed “about 95 percent” of the team’s work for the past six months.
“We are busier than we have ever been,” O’Neill said. “Historically, our lab was targeting five-hundred-thousand to one million cells per experiment. Now we are consistently getting over two million nuclei per experiment, and have even projected eight million from one recent experiment!”
The number of experiments, combined with the use of AI in interpreting the resulting data, contribute to the unprecedented nature of the research.
“It’s exciting to see what this data set will enable,” O’Neill said. “This is a far larger scale than I have ever seen anyone do.”
[NOTE: BBI created its Single Cell Genomics Platform in 2018, when it started offering single-nucleus RNA-sequencing. In addition to the work related to the Seattle Hub for Synthetic Biology and the Billion Cells Project, it has served individual researchers, as well as contributed to other large-scale efforts, including the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and some of the largest single cell atlases for human development, as well as model organisms, such as mice and rhesus macaques. For more information, contact, Dr. Mary O’Neill at oneillmb@uw.edu]
