Who You Are Versus Where You Are

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Science  18 May 2007:
Vol. 316, Issue 5827, pp. 957
DOI: 10.1126/science.316.5827.957c

The ability to identify essential components by network analysis may provide one means of ranking targets for disrupting specific cellular processes. Yu et al. have assessed the relative importance of being a hub (that is, being a highly connected node) in comparison to being a bottleneck, a node that serves as a conduit for nonredundant paths through the network. These attributes do overlap, but they were able to find all four types of nodes in large-scale protein-protein interaction maps: hub-bottleneck, nonhub-bottleneck, hub-nonbottleneck, and nonhub-nonbottleneck. For instance, in signaling networks, hub-bottlenecks and nonhub-bottlenecks were likely to be encoded by essential genes, whereas hub-nonbottlenecks were not. Thus, being a bottleneck may be a better indicator of necessity than the degree of connectedness. A refinement of the nonhub-bottleneck nodes was achieved by dividing them into those that participate in permanent interactions, such as those that hold multisubunit complexes together, versus those that mediate transient protein-protein interactions. Not surprisingly, permanent nodes were more likely to be encoded by an essential gene than were the transients. Furthermore, the authors suggest that nonhub-bottlenecks are key to pathway crosstalk. Cak1p, which is encoded by an essential gene in yeast and is a cyclin-dependent protein kinase-activating kinase, is offered as an example of a nonhub-bottleneck that is the critical link between two signaling pathways: regulation of the cell cycle and sporulation. — NRG

PLoS Comp. Biol. 3, e59 (2007).

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