Development and application of a computational approach to align protein interaction networks

This thesis describes the development of PINALOG, a protein interaction network alignment method, and its application to the area of protein function prediction and protein complex detection. Protein-protein interactions (PPI) play an important role in the function of biological processes. Advances in high-throughput technology have produced a large amount of protein-protein interaction data, enabling analyses at the system level. Although protein-protein interaction networks (PPINs) vary between species, there are components of them that perform similar biological functions and these are likely to be conserved across species. Comparison of the protein interaction networks from different species yields understanding of the evolution of species, as well as a means to predict protein function and conserved components. An alignment method, PINALOG, has been developed which globally aligns the similar parts of the networks using information from protein sequences, protein functions and network topology in a seed-and-extend framework. The results on human and yeast network alignment revealed conserved subnetworks that are components of similar biological processes such as the proteasome or transcription related processes. The alignments of several pairs of species confirm the superior performance of PINALOG over commonly used methods such as Graemlin and IsoRank in terms of finding a large conserved network as well as detecting biologically meaningful mappings of the proteins in the two aligned species. The alignment method also suggested an approach to perform protein complex prediction by knowledge transfer from one species to another. In addition the implications for function prediction of proteins in the "twilight" zone where there is little or no sequence similarity were explored. A web server for PINALOG was developed to provide users access to the alignment method.EThOS - Electronic Theses Online ServiceGBUnited Kingdo