Publications - Published papers

Please find below publications of our group. Currently, we list 506 papers. Some of the publications are in collaboration with the group of Sonja Prohaska and are also listed in the publication list for her individual group. Access to published papers (access) is restricted to our local network and chosen collaborators. If you have problems accessing electronic information, please let us know:

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Prediction of lethal and synthetically lethal knock-outs in regulatory networks

Gunnar Boldhaus, Florian Greil, Konstantin Klemm

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Theory in Biosciences 132:17-25 (2013)

Abstract


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.

Keywords


knock-out, synthetic lethality, prediction, network centrality, Boolean network