First - this was a bi-coastal, multi-lab project w/ many folks to recognize including fellow blueskyers: @erinweisbart.bsky.social @bethcimini.bsky.social @shantanu-singh.cc @juliabauman.bsky.social @skavari.bsky.social @drannecarpenter.bsky.social - ThreadSky

jtneal.bsky.social • 30 days ago

First - this was a bi-coastal, multi-lab project w/ many folks to recognize including fellow blueskyers: @erinweisbart.bsky.social @bethcimini.bsky.social @shantanu-singh.cc @juliabauman.bsky.social @skavari.bsky.social @drannecarpenter.bsky.social

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jtneal.bsky.social•30 days ago

For the last several years, a major focus of our lab has been building scalable tools to allow us to link genotypes to cellular programs at genome scale to understand gene and variant function in cancer and metabolic diseases.

jtneal.bsky.social•30 days ago

We’re big fans of using expression-based profiling (specifically Perturb-seq) to generate high-dimensional phenotypic profiles of perturbed cells, and w/ @oana-ursu.bsky.social & @boehmjesse.bsky.social have used it successfully for generating variant effect maps (https://www.nature.com/articles/s41587-021-01160-7)

jtneal.bsky.social•30 days ago

Even so, and despite amazing recent advances in this space, such as https://www.cell.com/cell/fulltext/S0092-8674(22)00597-9 from @weissmanlab.bsky.social, these studies can still be quite difficult to execute at genome-scale. So we turned to another approach: optical fluorescence imaging.

jtneal.bsky.social•30 days ago

Cell images, especially multicolor fluorescence images, are an immense source of phenotypic information, and thanks to approaches like Cell Painting from @drannecarpenter.bsky.social , we can extract this information as quantitative features (size, shape, texture, etc.) in automated fashion.

jtneal.bsky.social•30 days ago

Such data can be generated easily & cheaply, but historically hasn’t been ideal for large-scale functional genomics because imaging experiments could not use pooled genetic perturbation libraries (no way to optically determine which cell received which perturbation).

jtneal.bsky.social•30 days ago

Fortunately, the Blainey Lab and others solved this problem by developing methods to sequence individual perturbation barcodes using in situ sequencing, so we can now assign quantitative cell phenotypes AND barcodes to individual cells, enabling optical pooled screens. https://www.cell.com/cell/fulltext/S0092-8674(19)31067-0

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