Quantitative assessment of ligand bias from bias plots: The bias coefficient “kappa”

The current methods for quantifying ligand bias involve the construction of bias plots and the calculations of bias coefficients that can be compared using statistical methods. However, widely used bias coefficients can diverge in their abilities to identify ligand bias and can give false positives. As the empirical bias plots are considered the most reliable tools in bias identification, here we develop an analytical description of bias plot trajectories and introduce a bias coefficient, kappa, which is calculated from these trajectories. The new bias coefficient complements the tool-set in ligand bias identification in cell signaling research. •Ligand bias is the ability of ligands to differentially activate signaling pathways.•We introduce the bias coefficient “kappa” as a tool to identify ligand bias.•Kappa recapitulates the insights gained from bias plots.•Kappa allows statistical comparisons of the data.•Kappa can be used alongside other widely used bias coefficients.