Abstract
Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects.
Original language | English |
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Article number | e1000550 |
Journal | PLoS Computational Biology |
Volume | 5 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2009 Oct |
Externally published | Yes |
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Ecology
- Modelling and Simulation
- Molecular Biology
- Genetics
- Cellular and Molecular Neuroscience
- Computational Theory and Mathematics