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?

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?

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!?

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.

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.