Synergistic and Antagonistic Drug Combinations Depend on Network Topology
文献类型：期刊论文
| 作者 | Yi, Ning1; Ma, Wenzhe5; Pei, Jianfeng1; Ouyang, Qi1,3,4; Tang, Chao1,3,4; Lai, Luhua1,2,3 |
| 刊名 | PLOS ONE
 |
| 出版日期 | 2014-04-08 |
| 卷号 | 9期号:4 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0093960 |
| 英文摘要 | Drug combinations may exhibit synergistic or antagonistic effects. Rational design of synergistic drug combinations remains a challenge despite active experimental and computational efforts. Because drugs manifest their action via their targets, the effects of drug combinations should depend on the interaction of their targets in a network manner. We therefore modeled the effects of drug combinations along with their targets interacting in a network, trying to elucidate the relationships between the network topology involving drug targets and drug combination effects. We used three-node enzymatic networks with various topologies and parameters to study two-drug combinations. These networks can be simplifications of more complex networks involving drug targets, or closely connected target networks themselves. We found that the effects of most of the combinations were not sensitive to parameter variation, indicating that drug combinational effects largely depend on network topology. We then identified and analyzed consistent synergistic or antagonistic drug combination motifs. Synergistic motifs encompass a diverse range of patterns, including both serial and parallel combinations, while antagonistic combinations are relatively less common and homogenous, mostly composed of a positive feedback loop and a downstream link. Overall our study indicated that designing novel synergistic drug combinations based on network topology could be promising, and the motifs we identified could be a useful catalog for rational drug combination design in enzymatic systems. |
| 语种 | 英语 |
| WOS记录号 | WOS:000334160900067 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/51277]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Lai, Luhua |
| 作者单位 | 1.Peking Univ, Ctr Quantitat Biol, Beijing 100871, Peoples R China 2.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, BNLMS, Beijing 100871, Peoples R China 3.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China 4.Peking Univ, Sch Phys, Beijing 100871, Peoples R China 5.Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA |
| 推荐引用方式 GB/T 7714 | Yi, Ning,Ma, Wenzhe,Pei, Jianfeng,et al. Synergistic and Antagonistic Drug Combinations Depend on Network Topology[J]. PLOS ONE,2014,9(4). |
| APA | Yi, Ning,Ma, Wenzhe,Pei, Jianfeng,Ouyang, Qi,Tang, Chao,&Lai, Luhua.(2014).Synergistic and Antagonistic Drug Combinations Depend on Network Topology.PLOS ONE,9(4). |
| MLA | Yi, Ning,et al."Synergistic and Antagonistic Drug Combinations Depend on Network Topology".PLOS ONE 9.4(2014). |
入库方式： OAI收割
来源：化学研究所
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