Phenotype overlap. A) Shaded circles represent sets of measured values of a subset of all phenotypic attributes. Asterisks represent the conceptual aspect of interest: drug clearance. They encompass the set of derived measures related to drug clearance, though measurements and their generative mechanisms may different among model systems. There is clear overlap of some measured attributes of an isolated, perfused rat liver (green circle) and corresponding human hepatocytes in situ (orange circle). The same can be said of in vitro hepatocyte culture cells (blue circle) and an isolated, perfused rat liver. In non-overlapping regions, the mapping between related attributes is complex. B) The ISL and ISHC (dark purple circles) are in silico analogs with their own measurable phenotypes. Overlapping regions represent targeted attributes that have achieved quantitative measures of similarity. The light purple connecting the two analogs illustrates that the transformation between the ISL and ISHC need not be one-to-one. Exploring ISL-ISHC transformations may be instructive of the transformation that occurs between when in vivo cells are isolated into in vitro cultures.