SBML Level 3: an extensible format for the exchange and reuse of biological models

Abstract

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.

Keywords: computational modeling; file format; interoperability; reproducibility; systems biology.

Figure 1. SBML Level 3 (Hucka et al, 2019) consists of a core (center) and specialized SBML Level 3 packages (in blue), which provide syntactical constructs to support additional modeling approaches

The packages support new types of modeling (in the gray boxes) needed for large and complex models such as those used in various domains and fields of biology (in the light red boxes). The meanings of SBML package labels such as “fbc” are given in Table 1, with additional package information in Box  1.

Figure 2. A closer look at SBML

(A) Fragments of the global structure of an SBML file. In this example, the use of several SBML packages is declared in the file header. Model elements in the file include the descriptions of model variables, as well as their relationships. Elements of the same type are collected into “ListOf” elements; model parameters are in the ListOfParameters element. SBML package elements can refer to elements in the SBML Core as necessary. (B) Model elements are linked through unique identifiers used in the mathematical constructs and the elements describing the reactions, the molecular species, and their localization. The full model for this example is available in BioModels Database (Malik‐Sheriff et al, 2020) as the model with identifier MODEL1904090001.