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Cancer onset and progression: a genome-wide, nonlinear dynamical systems perspective on onconetworks.
1Center for Cell and Virus Theory, Department of Chemistry, Indiana University, Bloomington, IN 47405-7102, USA.
Journal of Theoretical Biology
|February 10, 2007
Summary
Human cell types arise from nonlinear dynamical systems (NDS) governing transcriptional regulatory networks (TRN). Understanding these complex "bifurcation nexus" states and "onconetworks" is key to comprehending cell transitions and cancer.
Area of Science:
- Systems Biology
- Genomics
- Computational Biology
Background:
- Human cell diversity is vast, with cells existing in multiple states.
- Transcriptional regulatory networks (TRNs) are fundamental to cellular function and state determination.
Purpose of the Study:
- To investigate the hypothesis that nonlinear dynamical systems (NDS) underlie cellular states.
- To analyze the complexity of TRNs and their role in cell state transitions.
- To identify potential
- onconetworks
- involved in cancer.
Main Methods:
- Integrated TRN databases, microarray data, bioinformatics, kinetic modeling, and NDS analysis software.
- Developed a quantitative measure for TRN complexity, termed
- bifurcation nexus
- .
- Simulated point mutations to observe their effect on cellular states.
Main Results:
- Validated the NDS hypothesis for epithelial cells, revealing a complex
- bifurcation nexus
- .
- Demonstrated that cells can persist in states or transition between them, with potential for reversing seemingly irreversible changes.
- Showed that minor genetic changes can lead to significant state transitions due to cross-linked TRN structures.
Conclusions:
- Cellular states and transitions are governed by complex, interconnected TRNs.
- Understanding
- onconetworks
- is crucial for cancer research, moving beyond single oncogene studies.
- This systems-level approach provides new insights into cell fate determination and disease mechanisms.
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