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| Content Provider | IEEE Xplore Digital Library |
|---|---|
| Author | Haijun Gong Lu Feng |
| Copyright Year | 2014 |
| Description | Author affiliation: Dept. of Math. & Comput. Sci., St. Louis Univ., St. Louis, MO, USA (Haijun Gong; Lu Feng) |
| Abstract | Endoplasmic reticulum (ER) is a communication hub for several signaling and secretory pathways that regulate the cell cycle progression. Recent studies revealed that deregulation of ER stress-induced signaling pathways are involved in the patho-genesis of cancer and Alzheimers disease. Computational analysis and verification of these pathways will provide insights into the mechanism linking ER stress with different diseases. Based on the experimental observation and our recent bioinformatics studies, we construct a quantitative model to systematically study the ER stress-induced apoptosis and survival signaling pathways. To overcome the limitations of traditional simulation techniques, a formal verification method, called Probabilistic Model Checking, was introduced and applied to formally analyze the temporal logic properties of the stochastic model, which is written in the PRISM language. Compared with the symbolic model verification method, this PRISM verification technique can not only qualitatively verify the signaling pathway model using sequential probability ratio test (SPRT), but also provide a quantitative estimation of the temporal properties using confidence interval estimation method. The probabilistic verification studies show that, overexpressed ER transmembrane proteins will promote the expression of Cyclin D, Amyloid-β and MDM2, leading to the pathogenesis of cancer and other diseases in the long term, and inhibit the apoptosis. Our work also verified that, varying IKK's expression level will influence the number of NFκB molecules in the nucleus, which explained why IKK inhibitor could inhibit tumorigenesis. The proposed signaling pathway model and PRISM method can help our understanding of the mechanisms that link ER stress with cancer and other diseases. |
| Starting Page | 182 |
| Ending Page | 187 |
| File Size | 488355 |
| Page Count | 6 |
| File Format | |
| ISBN | 9781479956692 |
| DOI | 10.1109/BIBM.2014.6999149 |
| Language | English |
| Publisher | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
| Publisher Date | 2014-11-02 |
| Publisher Place | UK |
| Access Restriction | Subscribed |
| Rights Holder | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
| Subject Keyword | confidence Interval sequential probability ratio test Estimation ER stress signaling pathway Probabilistic verification PRISM Stress Diseases Proteins Feedback amplifiers cancer Alzheimer's disease Erbium Cancer |
| Content Type | Text |
| Resource Type | Article |
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