Finally, we wondered if we could predict how drugs combine, and found that some cells are predicted to respond synergistically to combinations of BH3-mimetics. We tested this exciting prediction with new experiments in the lab and were so happy to see the same result.

We found the exact same approach works with a library of cell lines, that all respond differently to BH3-mimetics.
Simulations gave accurate predictions of the which is the right drug for the right DLBCL cell line. Predictions get even better when we consider mutations.

A: Yes!
We used initial conditions from IPs and Co-IPs. We modelled cell-to-cell variability, which we measured before (https://pnas.org/doi/10.1073/pnas.1715639115). Simulations correctly predicted the most effective drugs.
Okay, so it works with one cell line, but they all respond so differently!?

A: Sadly not with existing models of apoptosis :(
So Ielyaas, thanks to many chats with experts in apoptotsis, built a math model focusing on the the mitochondrial membrane and its complex interaction network.
First test: can we predict how a cell line responds to drugs?

The work was inspired by a great paper from Martin Dyer's group in Leicester.
(https://haematologica.org/article/view/9988) where they show that response to BH3-mimetics is not as simple as more MCL1=better response to MCL1-targeting inhibitors. But in fact a complex interaction network is at play.
Q: Can we model this?