Developing a vision for executing scientifically useful virtual biomedical experiments

A virtual biomedical experiment (VBE) is a simulation of a wet-lab or clinical biomedical experiment. The goal of VBEs is to provide a scientifically useful method of in silico experimentation that can challenge concrete hypotheses and provide explanatory, mechanistic insight into the referent system. We envision virtual experimentation not as a supplement to traditional wet-lab experimentation, but rather as an essential part of the scientific method itself. The goal of this work is to lay preliminary groundwork for realizing this vision, through outlining requirements and describing agentbased models demonstrative of this vision. VBEs focus on reasoning by analogy; thus, a VBE includes model components analogous to particular relevant aspects of the referent experiment—from hypothesis formation to data analysis, and key concepts in between. We explore five exemplary categories of scientifically useful VBEs: hypothesis, experiment context, living counterparts, experiment agents, and measurements. We discuss how to develop model components of each category in the context of agent-based modeling. We highlight the importance of two overarching requirements: concreteness and modularity. Finally, we demonstrate this vision by describing an in silico liver model that partially fulfills the VBE vision and requirements, including components corresponding to each of the five VBE categories.