Title: Two scenarios for overcoming drug resistance by co-targeting

Authors: Golnaz Taheri; Marzieh Ayati; Limsoon Wong; Changiz Eslahchi

Addresses: School of Mathematics and Computer Science and Center of Excellence in Bioinformatics, College of Science, University of Tehran, Tehran, Iran; Institute for Research in Fundamental Sciences (IPM), Tehran, Iran ' Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, OH 44106, USA ' Department of Computer Science, National University of Singapore, Singapore ' Department of Computer Science, Shahid Beheshti University G.C., Tehran, Iran

Abstract: Removal of proteins on an essential pathway of a pathogen is expected to prohibit the pathogen from performing a vital function. To disrupt these pathways, we consider a cut set S of simple graph G, where G representing the PPI network of the pathogen. After removing S, if the difference of sizes of two partitions is high, the probability of existence of a functioning pathway is increased. We need to partition the graph into balanced partitions and approximate it with spectral bipartitioning. We consider two scenarios: in the first, we do not have any information on drug targets; in second, we consider information on drug targets. Our databases are E. coli and C. jejuni. In the first scenario, 20% and 17% of proteins in cut of E. coli and C. jejuni are drug targets and in the second scenario 53% and 63% of proteins in cut are drug targets respectively.

Keywords: essential pathways; protein protein interaction; PPI networks; balanced bipartitioning; drug targets; pathogens; drug resistance; co-targeting; bioinformatics; E. coli; C. jejuni.

DOI: 10.1504/IJBRA.2015.067338

International Journal of Bioinformatics Research and Applications, 2015 Vol.11 No.1, pp.72 - 89

Available online: 06 Feb 2015 *

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