When Giovanna Prout, president and CEO of Scale Bio, thinks about single cell technology, she thinks big. (Meaning, a lot of cells.) And she wants researchers to think big with her. To that end, a few months ago, she developed a plan that would inspire researchers to submit proposals for experiments that they have always wanted to do, but couldn’t because of cost or logistics. Not only that, but she created a way to support those proposals, as well.
Together with her team at Scale Bio, she established the 100 Million Cell Challenge. But Scale Bio couldn’t do it alone; they needed collaborators. Soon after the idea was born, the Chan Zuckerberg Initiative (CZI; funding), Ultima Genomics (sequencing), NVIDIA (compute power), and BioTuring (access to their advanced analysis platform, BBrowserX) joined the initiative to collaborate and subsidize costs of the projects.
They solicited proposals and, recently, at the ASHG meeting in Denver, CO, the team announced the 14 winners; the projects span across diverse applications, addressing critical challenges in global health—from childhood respiratory diseases to cancer disparities.
The initiative ended up drawing 147 different proposals, totaling nearly one billion cells, from researchers in 27 countries. The project, Prout said, is showcasing that there is a demand “for these really large-scale initiatives.”
The number of submissions “blew her away,” Prout told GEN. At first, she expected that they would get somewhere in the range of 30 projects. So, when more than 140 came in, “it was really exciting to see the demand.” There were submissions from established single cell researchers limited by their current technology. There were also proposals from researchers new to single cell—scientists who wanted to try single cell, but it has been too expensive or too intimidating to get started.
Scale Bio, located in San Diego, CA, has developed a massively parallelized single cell barcoding technology. The large-scale projects will utilize the company’s newest technologies, QuantumScale, a single cell RNA sequencing technology, and ScalePlex, a multiplexing technology that enables seamless sample pooling. Together, these technologies enable researchers to multiplex samples and prepare up to two million cells in parallel.
Scale plans to go to the researchers’ labs to help them fix and prepare their cells, which will be shipped to Scale Bio. Scale will then process them and send the libraries to Ultima Genomics, in Fremont, CA, for sequencing. The data will then be sent back to the researchers.
The winning projects will be fully subsidized by the CZI where Jonah Cool, PhD, cell science senior program officer, led the initiative. The remaining proposals have been offered subsidized projects, for their willingness to submit an application. “We didn’t want to leave them hanging,” noted Prout. “At the end of the day, this is really all about their science and trying to enable them as much as possible.”
Data from the winning projects will be made openly available on CZ CELL by GENE Discover and will accelerate modeling efforts including CZI’s commitment to build AI-powered virtual cell models, capable of predicting the behavior of healthy and diseased cells.
“The scale of these single cell omics projects will enhance Chan Zuckerberg CELL by GENE Discover—a platform CZI built where scientists can explore curated cellular data and discover new information—making it an even more powerful resource for the global research community,” said Cool. “Each cell analyzed brings us closer to understanding diverse populations, complex diseases, and how to develop more effective treatments.”
The selected projects span a remarkable range of applications, from expanding the first global atlas of pediatric health to investigating population-specific differences in cancer outcomes. Collectively, they demonstrate how increased scale in single cell analysis can transform our understanding of human biology and disease.
Prout says that they focused on a few areas: studying diversity and different populations that may be underrepresented: finishing biology by studying systems or tissue types that have been underrepresented (for example in the Human Cell Atlas) to interrogate healthy tissues to a level that other tissues have been interrogated: and drug screening projects to showcase high numbers of conditions across many cells and build foundation models off of that.
“When researchers can analyze millions of cells instead of thousands,” said Prout, “we unlock entirely new possibilities for understanding human health and disease.”
For more updates on the project, please check here.
The winners:
Winning projects were selected to reflect four key priorities in biomedical research:
- Global Health Equity: Studies spanning multiple continents and diverse populations across age and ancestry
- Disease Characterization: Looking at many patients and tissues temporally to fully understand disease-specific mechanisms
- Cancer Biology: New approaches to understanding treatment responses
- Therapeutic Innovation: Novel platforms for disease perturbations and drug development
The projects selected for full subsidy include:
- Federico Gaiti, University Health Network, Elucidating Molecular Dependencies of Glioblastoma Cells Engaged in Neuronal Crosstalk
- Caleb Webber, UK Dementia Research Institute, Zebrafish Whole Brain Disease Modeling
- Sophia George, University of Miami, African Caribbean Single Cell NetwRork
- Kevin Matthew Byrd, Virginia Commonwealth University, Mapping the Pediatric Inhalation Interface at Single Cell Resolution
- David van Heel, Genes & Health/Queen Mary University of London, Genes & Health, Multiomics
- Tom Taghon, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Molecular Drivers of Human T Cell Development
- Drew Neavin, Garvan Institute of Medical Research, Identifying Patients at Risk of Drug-Induced Cardiotoxicity
- Luis Barreiro, University of Chicago, Unveiling Immune Variation Across Diverse Human Populations
- Barbara Treutlein, ETH Zurich, Predictive Modeling of Cell State-Specific Responses to Small Molecule Perturbations in Human Organoids
- Zack Lewis, Allen Institute for Brain Science, Sympathetic Nervous System Atlas
- John Tsang, Yale University/Chan Zuckerberg Biohub New York, Deciphering the Immune Health of Global Populations
- Constantine Tzouanas, MIT, Protein Platform Perturbing Human PBMCs with Transcriptomic Readout
- Christine Disteche, University of Washington, Single Cell Transcriptome Analyses of Sex Differences in Normal Human Development and in Genetic Conditions with an Abnormal Number of Sex Chromosomes
- April Foster, Wellcome Sanger Institute, Signalling Perturbations to Understand Human Development
