Prospects and problems for standardizing model validation in systems biology

Abstract

There are currently no widely shared criteria by which to assess the validity of computational models in systems biology. Here we discuss the feasibility and desirability of implementing validation standards for modeling. Having such a standard would facilitate journal review, interdisciplinary collaboration, model exchange, and be especially relevant for applications close to medical practice. However, even though the production of predictively valid models is considered a central goal, in practice modeling in systems biology employs a variety of model structures and model-building practices. These serve a variety of purposes, many of which are heuristic and do not seem to require strict validation criteria and may even be restricted by them. Moreover, given the current situation in systems biology, implementing a validation standard would face serious technical obstacles mostly due to the quality of available empirical data. We advocate a cautious approach to standardization. However even though rigorous standardization seems premature at this point, raising the issue helps us develop better insights into the practices of systems biology and the technical problems modelers face validating models. Further it allows us to identify certain technical validation issues which hold regardless of modeling context and purpose. Informal guidelines could in fact play a role in the field by helping modelers handle these.