A new centrality of the nodes in the network is proposed called alternate centrality, which can isolate effective drug targets in the complex signalling network. Alternate centrality metric defined over the network substructure (four nodes - motifs). The nodes involving in alternative activation in the motifs gain in metric values. Targeting high alternative centrality nodes hypothesised to be destructive free to the network due to their alternative activation mechanism. Overlapping and crosstalk among the gene products in the conserved network of MAPK pathways selected for the study. In silico knock-out of high alternate centrality nodes causing rewiring in the network is investigated using MCF-7 breast cancer cell line-based data. Degree of top alternate centrality nodes lies between the degree of bridging and pagerank nodes. Node deletion of high alternate centrality on the centralities such as eccentricity, closeness, betweenness, stress, centroid and radiality causes low perturbation. The authors identified the following alternate centrality nodes ERK1, ERK2, MEKK2, MKK5, MKK4, MLK3, MLK2, MLK1, MEKK4, MEKK1, TAK1, P38alpha, ZAK, DLK, LZK, MLTKa/b and P38beta as efficient drug targets for breast cancer. Alternate centrality identifies effective drug targets and is free from intertwined biological processes and lethality.

中文翻译：

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拓扑交替中心性测量捕获 MAPK 通路网络中的药物靶标。

提出了网络中节点的一种新的中心性，称为替代中心性，它可以在复杂的信号网络中隔离有效的药物靶点。在网络子结构（四个节点 - 主题）上定义的替代中心性度量。参与主题中替代激活的节点会获得度量值。针对高替代中心性节点，假设由于其替代激活机制而对网络无破坏性。研究所选 MAPK 通路保守网络中基因产物之间的重叠和串扰。使用基于 MCF-7 乳腺癌细胞系的数据，对导致网络中重新布线的高替代中心性节点进行计算机剔除进行了研究。顶部备用中心度节点的度数位于桥接节点度数和 pagerank 节点度数之间。偏心度、接近度、介数、应力、质心和径向度等中心性上的高交替中心性的节点删除会导致低扰动。作者确定了以下替代中心节点 ERK1、ERK2、MEKK2、MKK5、MKK4、MLK3、MLK2、MLK1、MEKK4、MEKK1、TAK1、P38alpha、ZAK、DLK、LZK、MLTKa/b 和 P38beta 作为乳腺癌的有效药物靶点。交替中心性可识别有效的药物靶点，并且不受相互交织的生物过程和致死性的影响。