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Multi-omic Advancement In High-throughput Screening: From Imaging Phenome To Precision Medicine In 2D, 3D, And Beyond

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posted on 2024-12-18, 11:42 authored by Xiang Mark Li, Milton MuiMilton Mui, Xin LiuXin Liu, Simon Stuart Craig, Jennii Luu, Susanne RammSusanne Ramm, Tim Semple, Jason Li, Nick Clemons, Kaylene J. Simpson

The integration of advanced high content microscopy, sequencing technologies, and other high throughput platforms has created a powerful framework for exploring drug responses in multiomic dimensions. This study presents an integrated approach named MAC-seq (multiplexed analysis of cells) that combines high-throughput imaging with RNA sequencing in 384-well format across various cellular models, including adherent cells, organoids, and advanced 3D co-culture systems (Li et al., 2023).

Using 2D adherent and 3D spheroid cell models treated with tool compound libraries, we demonstrated how MAC-seq coupled cell painting-based morphological profiling with parallel transcriptomic data. This strategy offers a much deeper understanding of cellular responses, particularly the imaging features derived phenotypic clusters.

We further adapted this workflow to a high throughput, CAR T cell mediated cytotoxicity assay co-cultured with patient derived tumour spheroids. Live cell imaging captured kinetic differences between CAR-T and untransduced T-cells (UTD). By tracking individual spheroids, the method preserves the tumour heterogeneity and their responses to CAR-T therapy. Furthermore, transcriptomics revealed co-cultured CAR-T cells had distinct biological activity profiles in contrast to CAR-T cells alone or UTD co-culture samples, underscoring the importance of complex culture systems for translational precision medicine.


Poster presented as part of the Crick BioImage Analysis Symposium 2024.

Permission has been given by authors to upload to Crick Figshare. Copyright remains with the original authors.

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