SysBio modelica library

SysBio modelica library implements object-oriented biological modeling components in Modelica to construct comprehensive multi-pathway, multi-tissue systems-biology models for studying hepatic metabolism and related pathologies.

Key Features:

• Modelica implementation: Provides fundamental modeling objects and components implemented for the Modelica environment.
• Object-oriented modeling: Employs object-oriented modeling techniques to compose modular and reusable biological model components.
• Multi-pathway, multi-tissue support: Enables construction of models that integrate multiple metabolic pathways across hepatic and extra-hepatic tissues.
• Transcriptional and post-transcriptional regulation: Incorporates mechanisms for transcriptional and post-transcriptional regulation within metabolic models.
• Normalized steady-state operation: Supports operation at a normalized steady state without requiring detailed kinetic parameter constraints.
• Flux disturbance analysis: Facilitates identification of flux disturbances that can be compared to experimental observations.
• SteatoNet example model: Includes SteatoNet, a multi-pathway, multi-tissue in silico model of hepatic metabolism demonstrating the library’s capabilities.
• Pathway branch identification: Enables analysis that identified glucose, lipid, and ketone body transport branches as drivers toward hepatic steatosis.
• Cholesterol and transcriptional regulator analysis: Highlights cholesterol metabolism and transcriptional regulators as factors contributing to steatosis.

Scientific Applications:

• Hepatic metabolism modeling: Construction and analysis of comprehensive hepatic metabolic network models.
• Non-alcoholic fatty liver disease (NAFLD) research: Investigation of mechanisms and pathway perturbations leading to hepatic steatosis.
• Flux analysis and validation: Identification and comparison of model-predicted flux disturbances with data from liver patients and animal models.
• Regulatory mechanism studies: Exploration of transcriptional and post-transcriptional regulation impacts on metabolism, including cholesterol-related effects.

Methodology:

The library implements object-oriented components in Modelica, integrates transcriptional and post-transcriptional regulation, supports normalized steady-state formulations without detailed kinetic parameters, and enables identification of flux disturbances for comparison with experimental and animal model data.