Abstract
Drugs against multiple targets may overcome the many limitations of single targets and achieve a more effective and safer control of the disease. Numerous high-throughput experiments have been performed in this emerging field. However, systematic identification of multiple drug targets and their best intervention requires knowledge of the underlying disease network and calls for innovative computational methods that exploit the network structure and dynamics. Here, we develop a robust computational algorithm for finding multiple target optimal intervention (MTOI) solutions in a disease network. MTOI identifies potential drug targets and suggests optimal combinations of the target intervention that best restore the network to a normal state, which can be customer designed. We applied MTOI to an inflammation-related network. The well-known side effects of the traditional non-steriodal anti-inflammatory drugs and the recently recalled Vioxx were correctly accounted for in our network model. A number of promising MTOI solutions were found to be both effective and safer.
Original language | English (US) |
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Article number | 228 |
Journal | Molecular systems biology |
Volume | 4 |
DOIs | |
State | Published - 2008 |
Externally published | Yes |
Keywords
- Anti-inflammatory
- Arachidonic acid metabolic network
- Drug efficacy prediction
- Multiple target drug design
- Network-based drug design
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- Information Systems
- Applied Mathematics
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
- Computational Theory and Mathematics