SINEC : large scale signaling network topology reconstruction using protein - protein interactions and RNAi data

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2012

Author

Hashemikbahir, Seyedsasan

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Reconstructing the topology of a signaling network by means of RNA interference (RNAi) technology is an underdetermined problem especially when a single gene in the network is knocked down or observed. In addition, the exponential search space limits the existing methods to small signaling networks of size 10-15 genes. In this thesis, we propose integrating RNAi data with a reference physical interaction network. We formulate the problem of signaling network reconstruction as finding the minimum number of edit operations on a given reference network. The edit operations transform the reference network to a network that satisfy the RNAi observations. We show that using a reference network does not simplify the computational complexity of the problem. Therefore, we propose an approach that provides near optimal results and can scale well for reconstructing networks up to hundreds of components. We validate the proposed method on synthetic and real datasets. Comparison with the state of the art on real signaling networks shows that the proposed methodology can scale better and generates biologically significant results.

Subject Keywords

Protein-protein interactions, RNA-protein interactions, Cellular signal transduction., Information theory in biology.

URI

http://etd.lib.metu.edu.tr/upload/12614586/index.pdf
https://hdl.handle.net/11511/21734

Collections

Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

S. Hashemikbahir, “SINEC : large scale signaling network topology reconstruction using protein - protein interactions and RNAi data,” M.S. - Master of Science, Middle East Technical University, 2012.