title: Two scenarios for overcoming drug resistance by co-targeting.
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.
authors: 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.
authors: Golnaz
authors: G
authors: Taheri
authors: Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Marzieh
authors: M
authors: Ayati
authors: Department of Computer Science, National University of Singapore, Singapore.
authors: Limsoon
authors: L
authors: Wong
authors: Department of Computer Science, Shahid Beheshti University G.C., Tehran, Iran.
authors: Changiz
authors: C
authors: Eslahchi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D003198:Computer Simulation; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000502:physiology; D008954:Models, Biological; D025941:Protein Interaction Mapping / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins
keywords: C jejuni; E coli; PPI networks; balanced bipartitioning; bioinformatics; co–targeting; drug resistance; drug targets; essential pathways; pathogens; protein protein interaction