Notes from Meeting 10/16

[gwaybio]

• Writing progress report
  • Megan and Tarun will send out for comments on final version
  • No figures necessary
  • Beth will add language around wild-type clonal vs. resistance signatures (4 subclusters in heatmap)
• Mixture experiment
  • If we titrate wild-type and resistant clones into the same dish, can we distinguish?
  • Will help to set baseline of models predicting one from the other
  • Add in some ground truth fluorescent marker
  • We can simulate this experiment in silico first
• Collecting more data
  • More bortezomib plates (with a mixture of wild-type and resistant clones on the same plate)
  • Low dose treatments to reduce dead cell effect and determine when we can start to isolate resistant populations
• Focus on Proteasome inhibitors
  • Collect Cell Painting using other proteasome inhibitors (one that just failed clinical trails, other that has been approved)
  • Answer question if resistance signature is the same across inhibitors? Is there a universal signature that represents proteasome inhibition resistance? What proportion of untreated cells have these conditions?
• Big Picture: Can we characterize all common resistance signatures via Cell Painting?
  • There is a paper in Cancer Cell that talks about them (there are a surprisingly few core resistance mechanisms) @mekelley, can you add this paper here? I couldn't seem to find.

[gwaybio]

From @annecarpenter

Do we see signatures for this drug or class of drugs in our existing datasets? If so, do those signatures match what we see between clones? In cells treated w proteasome inhibitors, SS says YES we do see dramatic effect but that's probably because the cell line in question is not resistant to the drug so the cells are just dying.

Look at images, what is going on for the second grouping of samples that is SO much not like the others? We suspect it's just the dominant parental cell phenotype but what about it is so different (ie can see something by eye? What's the most distinguishing feature vs the other groups?)

Priority: eliminate plate effects, test other drugs in THIS pathway so we can build a story around a pathway where we know what's going on.