Poster
Unpacking the Complexity of Inflammasome Biology with High Content Imaging & Machine Learning
February 20, 2023
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10 minute read
Spring is on a mission to build a technology engine that gives scientists superpowers to accelerate drug discovery.
Inflammasome biology is among the many biological processes that involve complex and convergent pathways, making target identification and drug action difficult to resolve with traditional approaches. Here, we demonstrate how machine learning and advanced multi-dimensional data analysis can be used to advance drug discovery by facilitating analysis of complex, physiologically relevant data at very high throughputs and extremely low costs.
We designed a series of high content imaging-based screening experiments on primary human PBMCs under physiological inflammasome activation conditions (flagellin and ATP) to develop novel machine learning based analytical tools.
Specifically, we built unique phenoprints for different biological compounds and pathways, identified novel single-cell phenotypes, and advanced 300+ drug candidates for 7+ targets to potential clinical programs.
Spring’s tooling enabled analysis of over 110M images of cells were analyzed across 100k unique donor, drug, and treatment condition combinations in order to develop multiple scoring rubrics designed to categorize compounds into novel inflammasome inhibitor classes whose mechanisms of action can be uniquely matched to relevant human pathologies.
View our poster presented at SLAS 2023
Scientists can now leverage Spring’s tools to characterize thousands of compounds by training models to enable resolution of a specific pathway.
This overall approach can forge an accelerated path to novel drug discovery for similarly complex and disease-relevant biological processes from a single compound screen – thus validating Spring’s suite of tools that gives scientists superpowers on their quest to find novel therapeutics.
AUTHORS
Daniel Chen, Michael Wiest, William Van Trump, Dat Nguyen, Tempest Plott, Elisa Cambronero, Wendy Cousin, Ben Komalo, Jarred Heinrich, Brandon White, Ben Kamens, Lauren Nicolaisen, Rachel Jacobson*, Christian Elabd