Research ArticleCOMPUTATIONAL BIOLOGY

Fault Diagnosis Engineering of Digital Circuits Can Identify Vulnerable Molecules in Complex Cellular Pathways

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Science Signaling  21 Oct 2008:
Vol. 1, Issue 42, pp. ra10
DOI: 10.1126/scisignal.2000008

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Finding Vulnerability

Vulnerability assessment methods, which are commonly used to test digital circuits, were applied to biological signaling networks to identify the molecules that when dysfunctional, would be most likely to disrupt the function of the network. Two signaling well-characterized networks were analyzed (one leading to caspase3 activation and apoptosis and a second leading to activation of p53) and the molecules known to be critical to the response were properly identified. In a third network of neuronal activation of the transcription factor CREB, this analysis led to the identification of Gαi and the P/Q-type calcium channel, which were then experimentally validated as critical molecules in this network.

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