Drug Synergy Matrix: Bliss Excess Independence, and Where Published Combination Data Lives
How the Bliss independence model scores a drug-combination dose matrix, and what public screens such as NCI ALMANAC can and cannot tell you.
Combination chemotherapy seeks therapeutic synergy — where two drugs produce an effect significantly greater than expected from independent additive action.
**1. Bliss Independence Model:** Assuming Drug A and Drug B act through mutually independent mechanisms:
E(expected) = E_A + E_B − (E_A × E_B)
Where E is the fractional cell death (0.0 to 1.0).
**2. Reading the Excess:** SciKeep reports the mean Bliss excess across the combination wells and labels it with reading-aid bands: above +10 percentage points strong synergy, above +3 moderate synergy, below −3 antagonism, otherwise additive. These bands are a convention, not a statistical test. To call synergy, run independent replicate matrices and test whether the excess differs from zero.
**3. Published Combination Screens:** The NCI ALMANAC (Holbeck et al., 2017) screened roughly 5,000 pairs of FDA-approved anticancer drugs across the NCI-60 cell line panel. It scores combinations with its own ComboScore rather than Bliss excess, so its numbers are not directly comparable to a Bliss score from your matrix. SciKeep does not bundle or look up ALMANAC data; use the NCI DTP portal to check whether your pair and cell line were screened.