Terminology summary
Biased ligand/signaling: In the broad context of an arbitrary reference ligand, this term solely denotes a difference relative to the reference ligand, which can in turn display any signaling. Hence, this is a normalized quantity, analogous to fold potency, percent efficacy or rank order relation. This term is receptor- and system-dependent and can only be used after an explicit prior definition separating receptor and system bias: e.g., “ligand L displays [recruitment/signaling/..] bias towards pathway P1 over pathway P2 relative to reference ligand A at receptor R in cell line C” (see section Unambiguous description of ligand bias – experiment information).
Unbiased ligand: A ligand that stimulates pathways in a manner indistinguishable from the reference ligand.

Pathway-biased ligands/signaling (using a pathway-balanced reference ligand)

When using a pathway-balanced reference ligand (typically a surrogate but could be an endogenous ligand) the statement that a tested ligand is biased carries the meaning that it preferentially activates one pathway over the other (Table 1).
Recommendation 3: Our recommendation here concerns which approaches to use to select a reference ligand which is balanced in its signaling (a definition limited to the given investigated systems and assays, see below). In an ideal case, the reference ligand would have identical concentration-response curves in the compared pathways. A way to quantify the similarity of pathway responses is to make a bias plot of an equimolar comparison of induced activities (Figure 2). The most balanced (least biased) ligand is then defined as the one with a slope closest to 1.
A database of expert-curated pathway-balanced reference ligands will soon be available in GPCRdb, and researchers can deposit their suggested reference ligands via a standardized Excel file detailing information about the pathways and assays to provide context-specific suggested reference ligands (download link).