title: Network-based approach reveals Y chromosome influences prostate cancer susceptibility.
abstract: The human Y chromosome contains a small number of genes that play a critical role in the determination of male-specific organs. Today's advances have provided valuable resources for defining the functions of this chromosome in both normal and cancerous prostates. Despite the fact that generation of high-throughput expression data is becoming usual; the systematic methods of data analysis in a biological context are still an impediment. Here we have shown that constructing co-expression networks using Y-chromosome genes provides an alternative strategy for the detection of new candidate genes involved in prostate cancer. In our approach, independent co-expression networks from normal and cancerous stages are reconstructed using a reverse engineering approach. We then highlight crucial pathways, biological processes, and genes involved in the prostate cancer by analyzing each network individually and in concert. Thus, we have identified 18 critical pathways and processes related to prostate cancer, many of which have previously been shown to be involved in cancer. In particular, we identify 22 Y-chromosome genes putatively linked to prostate cancer, 13 of which have been already verified experimentally. Our novel network-based approach is useful for accurate inference of processes and essential regulators that mediate molecular changes during cancer progression.
authors.affiliation: Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. Electronic address: khosravi@ibb.ut.ac.ir.
authors.forename: Pegah
authors.initials: P
authors.lastname: Khosravi
authors.affiliation: Institute of Parasitology, McGill University, Montreal, QC, Canada. Electronic address: vahid.gazestani@mcgill.ca.
authors.forename: Vahid H
authors.initials: VH
authors.lastname: Gazestani
authors.affiliation: Hematology-Oncology and Stem Cell Transplantation Research Centre, Shariati Hospital, Tehran, Iran. Electronic address: yazdan.asgari@alumni.ut.ac.ir.
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Asgari
authors.affiliation: The Donnelly Centre, University of Toronto, Toronto, Canada; Department of Computer Science, University of Toronto, Toronto, Canada. Electronic address: bm.law@utoronto.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Law
authors.affiliation: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; School of Biological Sciences, Institute for Research in Fundamental Sciences, Tehran, Iran. Electronic address: sadeghi@nigeb.ac.ir.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sadeghi
authors.affiliation: Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. Electronic address: bahram.goliaei@gmail.com.
authors.forename: Bahram
authors.initials: B
authors.lastname: Goliaei
mesh_terms: D041322:Chromosomes, Human, Y / Q000235:genetics*; D003198:Computer Simulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: Co-expression networks; Expression data; Prostate cancer; Reverse engineering approach; Y-chromosome genes