An illustration of similarities of in silico and in vitro model systems. An abstract, Venn-like diagram depicts overlapping sets of similar features of in silico and in vitro models. The larger circle is a set of observable, measurable, phenotypic attributes of the experimental in vitro flow chamber system. Attention is focused on selected aspects of the system, e.g., leukocyte interactions with the flow chamber surface. (A) a: each small shaded domain represents experimental measures of a specific in vitro characteristic or property such as distance rolled. The degree of shading illustrates different levels of experimental and measurement uncertainty. t: these are members of the set of targeted in vitro attributes that the in silico model is expected mimic. The shaded circle contains the much smaller set of observable, measurable attributes of a foundational in silico analogue, such as the ISWBC. (B) The sketch illustrates the systematic, sequential extension of the foundational analogue's attributes to improve model-referent phenotype overlap. Circle #1: The set of attributes targeted by the ISWBC in A (the foundational analogue). Circle #2 (shaded): The targeted attributes (represented by circle #1) have been expanded to include two new attributes; however, ISWBC #1 fails to generate behaviors similar to the two newly targeted attributes, resulting in its invalidation. A copy of the ISWBC is iteratively refined (without losing or breaking the original behaviors) by adding new detail only as needed (or by replacing an atomic component with a composite component) until successful coverage of the expanded set of targeted attributes is achieved. Oval #3 (dotted): The analogue represented by circle #2 is to be improved: one new attribute is added to the set of targeted attributes in 2, and the process just described is repeated.