Hypothesizing about signaling networks

The current knowledge about signaling networks is largely incomplete. Thus biologists constantly need to revise or extend existing knowledge. The revision and/or extension is first formulated as theoretical hypotheses, then verified experimentally. Many computer-aided systems have been developed to assist biologists in undertaking this challenge. The majority of the systems help in finding “patterns” in data and leave the reasoning to biologists. A few systems have tried to automate the reasoning process of hypothesis formation. These systems generate hypotheses from a knowledge base and given observations. A main drawback of these knowledge-based systems is the knowledge representation formalism they use. These formalisms are mostly monotonic and are now known to be not quite suitable for knowledge representation, especially in dealing with the inherently incomplete knowledge about signaling networks. We propose an action language based framework for hypothesis formation for signaling networks. We show that the hypothesis formation problem can be translated into an abduction problem. This translation facilitates the complexity analysis and an efficient implementation of our system. We illustrate the applicability of our system with an example of hypothesis formation in the signaling network of the p53 protein.