BSML: bio-synergy modeling language for multi-component and multi-target analysis

Multi-compound drugs are considered as the most promising solution to overcome the limited efficacy and off-target effect of drugs. However, identifying promising multiple compounds by experimental tests requires overwhelming costs and a number of tests. Systems biology-based approaches are regarded as one of the most promising strategy. To predict responses of drugs in biological systems is one of aims of Systems biology. We made Bio-Synergy Modeling Language (BSML) for modeling biological systems, which are multi-scale systems. BSML contains context information that covers spatial scales, temporal scales, and condition information, such as disease. We have applied BSML to generate type 2 diabetes (T2D) model, which involves malfunctions of numerous organs such as pancreas, liver, and muscle. We have extracted 12,522 T2D-related rules from public databases automatically. We simulated responses of single drugs and combination drugs on the T2D model by Petri nets. The results of our simulation show candidate T2D drugs and how combination drugs could act on whole-body scales. We expect that our work would provide an insight for identifying promising combination drugs and mechanisms of combination drugs on whole body scales.