Identifying the topology of signaling networks from partial RNAi data

Yuanfang Ren, Qiyao Wang, Md Mahmudul Hasan, Ahmet Ay, Tamer Kahveci

Methods for inferring signaling networks using single gene knockdown RNAi experiments and reference networks have been proposed in recent years. These methods assume that RNAi information is available for all the genes in the signal transduction pathway, i.e., complete. This assumption does not always hold up since RNAi experiments are often incomplete and information for some genes is missing. In this article, we develop two methods to construct signaling networks from incomplete RNAi data with the help of a reference network. These methods infer the RNAi constraints for the missing genes such that the inferred network is closest to the reference network. We perform extensive experiments with both real and synthetic networks and demonstrate that these methods produce accurate results efficiently. Application of our methods to Wnt signal transduction pathway has shown that our methods can be used to construct highly accurate signaling networks from experimental data in less than 100 ms. The two methods that produce accurate results efficiently show great promise of constructing real signaling networks.