Multiplexed perturbation screens facilitate a key prerequisite of "virtual cell" efforts: getting lots of perturbation data with detailed outputs. However, they present unique experimental design obstacles. 🧵 - ThreadSky

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ekernf01.bsky.social • 17 days ago

Multiplexed perturbation screens facilitate a key prerequisite of "virtual cell" efforts: getting lots of perturbation data with detailed outputs. However, they present unique experimental design obstacles. 🧵

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ekernf01.bsky.social•17 days ago

The usual screening approach for e.g. CRISPR screens involves sorting out the phenotype of interest, which only works for yes-no phenotypes. (2/n)

ekernf01.bsky.social•17 days ago

To scale up screens with a readout like Cell Painting or RNA-seq, people are starting to just stack up multiple perturbations on top of each other. (3/n)

ekernf01.bsky.social•17 days ago

This can kill the samples. For example, CRISPR with more than 12 target sites can produce >99% growth inhibition. https://pmc.ncbi.nlm.nih.gov/articles/PMC10103988/

ekernf01.bsky.social•17 days ago

How do we balance the need for cost savings (stack more perts per sample) against the chance of killing the samples? I wrote up various assumptions here.
https://ekernf01.github.io/multiplexed_perturbation_studies/ (5/n)

ekernf01.bsky.social•17 days ago

One set of assumptions leads to a really cute optimality result. If you screen N perturbations and expect K of them to each individually be lethal, then allocate each treatment to 1 out of every K+2 samples.

I thought that was nice. Hope you enjoyed it too.
(n/n)

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