  The complex interactions involved in regulation of a cell's function are
captured by its interaction graph. More often than not, detailed knowledge
about enhancing or suppressive regulatory influences and cooperative effects is
lacking and merely the presence or absence of directed interactions is known.
Here we investigate to which extent such reduced information allows to forecast
the effect of a knock-out or a combination of knock-outs. Specifically we ask
in how far the lethality of eliminating nodes may be predicted by their network
centrality, such as degree and betweenness, without knowing the function of the
system. The function is taken as the ability to reproduce a fixed point under a
discrete Boolean dynamics. We investigate two types of stochastically generated
networks: fully random networks and structures grown with a mechanism of node
duplication and subsequent divergence of interactions. On all networks we find
that the out-degree is a good predictor of the lethality of a single node
knock-out. For knock-outs of node pairs, the fraction of successors shared
between the two knocked-out nodes (out-overlap) is a good predictor of
synthetic lethality. Out-degree and out-overlap are locally defined and
computationally simple centrality measures that provide a predictive power
close to the optimal predictor.

Molecular Networks