Construction of a computable network model for DNA damage, autophagy, cell death, and senescence

Area of Science:

• Systems biology
• Toxicology
• Molecular biology

Background:

• Environmental toxicants pose risks to pulmonary and cardiovascular health.
• Systems toxicology approaches, like the "21st Century Toxicology" initiative, require computable biological network models.
• Previous work established foundational network models for toxicant exposure.

Purpose of the Study:

• To develop a systems biology-based risk assessment approach for environmental toxicants.
• To construct and evaluate a mechanistic network model of DNA damage response and cellular fates.
• To capture molecular events following toxicant exposure in non-diseased pulmonary and cardiovascular systems.

Main Methods:

• Building computable biological network models for specific cell types and tissues.
• Utilizing the Biological Expression Language (BEL) for semantic representation of life science relationships.
• Integrating 1231 PubMed-referenced literature citations to support network components.

Main Results:

• Construction and evaluation of a mechanistic network model focused on DNA damage response.
• The network comprises 34 sub-models, 1052 unique nodes, and 1538 unique edges.
• The model details four main cellular fates: autophagy, apoptosis, necroptosis, and senescence.

Conclusions:

• The developed network model provides a computable framework for understanding cellular responses to toxicants.
• This model advances systems toxicology by offering a detailed view of DNA damage and cell fate pathways.
• The network is available in .XGMML format for visualization with software like Cytoscape, facilitating further research.