Can’t you theoretically use both CellPainting assays and light-sheet microscopy?
I mean, I did look at CellPainting assays a small amount of time ago and I was still struck by how little control one had over the process, and how it isn’t great for many kinds of mechanistic interpretability. I know there’s a Brazil team looking at use of CellPainting for sphere-based silver-particle nanoplastics, but there are still many concrete variables, like intrinsic oxidative stress, that you can’t necessarily get from CellPainting alone.
CellPainter can be used for toxicological predictions of organophosphate toxicity (predicting that they’re more toxic than many other classes of compounds), but the toxicological assays used weren’t able to use much nuance, especially the kind that’s relevant to physiological concentrations that people are normally exposed to. I remember ketocozanole scored very highly on toxicity, but what does this say about physiological doses that are much smaller than the ones used for CellPainter?
Also, the cell lines were all cancer cell lines (OS osteosarcoma cancer cell lines), which gives little predictive power for neurotoxicity or a compound’s ability to disrupt neuronal signalling.
Still, the CellPainter support ecosystem is extremely impressive, even though it doesn’t produce Janelia-standard PB datasets that are used for lightsheet.. [cf https://www.cytodata.org/symposia/2024/ ]
FWIW, some of the most impressive near-term work might be whatever the https://www.abugootlab.org/ lab is going to do soon (large-scale perturb-seq combined with optical pooling to do readouts of genetic perturbations...)
Can’t you theoretically use both CellPainting assays and light-sheet microscopy?
I mean, I did look at CellPainting assays a small amount of time ago and I was still struck by how little control one had over the process, and how it isn’t great for many kinds of mechanistic interpretability. I know there’s a Brazil team looking at use of CellPainting for sphere-based silver-particle nanoplastics, but there are still many concrete variables, like intrinsic oxidative stress, that you can’t necessarily get from CellPainting alone.
CellPainter can be used for toxicological predictions of organophosphate toxicity (predicting that they’re more toxic than many other classes of compounds), but the toxicological assays used weren’t able to use much nuance, especially the kind that’s relevant to physiological concentrations that people are normally exposed to. I remember ketocozanole scored very highly on toxicity, but what does this say about physiological doses that are much smaller than the ones used for CellPainter?
Also, the cell lines were all cancer cell lines (OS osteosarcoma cancer cell lines), which gives little predictive power for neurotoxicity or a compound’s ability to disrupt neuronal signalling.
Still, the CellPainter support ecosystem is extremely impressive, even though it doesn’t produce Janelia-standard PB datasets that are used for lightsheet.. [cf https://www.cytodata.org/symposia/2024/ ]
https://markovbio.github.io/biomedical-progress/
FWIW, some of the most impressive near-term work might be whatever the https://www.abugootlab.org/ lab is going to do soon (large-scale perturb-seq combined with optical pooling to do readouts of genetic perturbations...)