Lab notes

What a failed screen taught us about packaged DNA

Nine hundred designs did nothing. The pattern in which ones did nothing turned out to be the most useful result of the year.

We ran twelve plates expecting a handful of hits. We got none. The first reaction in the lab was that something had gone wrong with the pipeline.

Checking the obvious

We re-ran two plates with a known-good control. The control worked, so the pipeline was fine and the designs really were inactive.

The pattern

When we sorted the inactive designs by where their target site sat relative to the nucleosome, the failures clustered. Designs aimed at the histone-facing side never worked.

What we did with it

That observation became the question behind our cryo-EM atlas, and the whole failed screen is in the supplement of that paper. Someone else will need it.

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