These screens generated rich phenotypic data, enabling us to use morphological profile similarity to explore relationships between perturbed genes such as clustering protein complex members by morphological similarity, and capturing membership/directionality of signaling pathways. - ThreadSky

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jtneal.bsky.social • 30 days ago

These screens generated rich phenotypic data, enabling us to use morphological profile similarity to explore relationships between perturbed genes such as clustering protein complex members by morphological similarity, and capturing membership/directionality of signaling pathways.

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jtneal.bsky.social•30 days ago

as well as identifying shared and media-specific responses to gene perturbation in cells cultured in DMEM vs human plasma-like media (HPLM).

jtneal.bsky.social•30 days ago

We were also able to use this clustering-by-morphological similarity information (plus mechanistic follow-up) to identify a role for the poorly characterized gene TMEM251 in lysosomal protein trafficking through the M6P-system.

jtneal.bsky.social•30 days ago

As an aside, though this finding was scooped by two concurrent papers in @science.org while we were preparing the preprint, it’s encouraging to see a hit from our unbiased imaging screen robustly validated by numerous groups!(https://www.science.org/doi/10.1126/science.abn5648, https://www.science.org/doi/10.1126/science.abn5637)

jtneal.bsky.social•30 days ago

In sum, pooled optical screens are a powerful approach for generating high-dimensional genotype-phenotype maps, and we demonstrate that these maps can now be generated routinely (and at a low cost per cell profile) at genome scale using standard imaging equipment and open source analysis pipelines.

jtneal.bsky.social•30 days ago

We believe this combination of accessibility and cost effectiveness make PERISCOPE-style screens a democratizing platform technology for linking genotypes to cellular programs.

jtneal.bsky.social•30 days ago

In addition, we present a draft genome scale atlas of human cell morphology containing more than 30 million perturbation-assigned cell images and high-dimensional single cell profiles.

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