Boolean model to experimental validation: A preliminary attempt

Abstract

There are several publications detailing modeling of biological systems, especially in the post-genomic era. However there is a real dearth of work testing and validating/invalidating mathematical models with experimental data. This work is one of the first attempts trying to bridge this expanding gap. Oxidative stress is a consequence of both normal and abnormal cellular metabolism and is linked to cell proliferation, differentiation and apoptosis through both genetic and epigenetic changes leading to the development of human diseases. Oxidative stress itself is a consequence of the imbalance between pro and anti-oxidative factors generated by cells in response to internal and external cues. A common mechanism for chemotherapeutic agents inducing cell death is through the induction of the generation of free radicals leading to an excess of free radicals. Although the exact mechanism of the molecular signaling that it entails is still being worked upon, however it is clear that this varies with the stage and type of cancer and the drug and dosage used. Key genes in the oxidative stress response pathways were earlier modeled by us using the multivariate Boolean Network Modeling. Here we studied the response of well accepted progressive breast cancer cell lines, the MCF10A series in response to Adriamycin and Cyclophosphamide, two well-known and commonly used chemotherapeutic drugs. We provide evidence that the strategy of using Boolean modeling and laboratory testing of the model, although not a perfect match, is certainly a reasonable one.