Type of bias Reference ligand Meaning (what can be concluded from data) Disclaimer (meanings/conclusion not supported by data)
Biased ligand / signaling Any ligand e.g., a candidate drug or tool compound. The reference ligand could be arbitrary, but often has a particular relevance as tool or clinical agent and is therefore selected to benchmark other, tested ligands. Simultaneous comparison across pathways and ligands where the reference ligand can be any ligand of choice. A biased ligand for which the reference ligand was not selected based on specific signaling pathway qualities has bias only relative to the reference ligand, which in itself can have any bias.
Pathway-biased ligand / signaling
Pathway-balanced ligand (defined in section Pathway-biased ligands/signaling)
Signaling preferentially via one pathway, as the reference ligand approximates a pathway-balanced signal.
A pathway-balanced/unbiased ligand can be physiology-biased, although it is by definition unbiased in the pathway definition. A balanced ligand in one system may not be ‘balanced’ in another (applies to all types of ligand bias).
Physiology-biased ligand / signaling
Principal endogenous agonist (defined in section Physiology-biased ligands/signaling)
Signaling differs from the natural/canonical, as the reference ligand represents the endogenous response (of the given receptor and system).
An endogenous agonist can be pathway-biased, although it is by definition unbiased in the physiological definition.