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Epithelial-mesenchymal plasticity at scale: AI-powered insights from single cells and spatial transcriptomics
The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterized. In this talk, I will describe AI-powered and ecology-inspired methods recently developed by us to provide a multi-scale view of the epithelial-mesenchymal plasticity in cancer from single cell and spatial transcriptomics data. First, we employed a large language model similar to the one underlying chatGPT but tailored for biological data (inspired by scBERT methodology), to predict individual stable states within the EMT continuum in single cell data and dissect the regulatory processes governing these states. Secondly, we leveraged spatial transcriptomics of breast cancer tissue to delineate the spatial relationships between cancer cells occupying distinct states within the EMT continuum and various hallmarks of the tumour microenvironment. We introduce a new tool, SpottedPy, that identifies tumour hotspots within spatial transcriptomics slides displaying enrichment in processes of interest, including EMT, and explores the distance between these hotspots and immune/stromal-rich regions within the broader environment at flexible scales. We use this method to delineate an immune evasive quasi-mesenchymal niche that could be targeted for therapeutic benefit. Our insights may inform strategies to counter immune evasion enabled by EMT and offer an expanded view of the coupling between EMT and microenvironmental plasticity in breast cancer.
Date:
21 February 2025, 11:00
Venue:
Mathematical Institute, Woodstock Road OX2 6GG
Venue Details:
L4
Speaker:
Prof Maria Secrier (UCL)
Organising department:
Mathematical Institute
Organiser:
Sara Jolliffe (University of Oxford)
Organiser contact email address:
jolliffe@maths.ox.ac.uk
Host:
Prof Helen Byrne (University of Oxford)
Part of:
Mathematical Biology and Ecology
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Sara Jolliffe
