The Evolution of Standards in Systems Biology: from Metabolic and Multi-Scale to Whole-Cell Models

A B S T R A C T The branches of systems biology focusing on mechanistic modeling have worked on standard-izing data formats and vocabularies for well over two decades, with seminal software packages, including GEPASI, dating back as to the early 1990s. Built on these standards, a rich ecosystem of model repositories and tools emerged, supporting everything from model exchange to automated reproduction of simulation results to visual representation of models. As the respective scientific communities grew, the standardization process itself became a matter of standardization. This review examines the current state of standardization across metabolic, multi-scale, and whole-cell modeling. We compare trajectories across these communities and comment on challenges to standardization characteristic of whole-cell modeling efforts.