title: Mirsynergy: detecting synergistic miRNA regulatory modules by overlapping neighbourhood expansion.
abstract: BACKGROUND
  Identification of microRNA regulatory modules (MiRMs) will aid deciphering aberrant transcriptional regulatory network in cancer but is computationally challenging. Existing methods are stochastic or require a fixed number of regulatory modules.
  
  
  RESULTS
  We propose Mirsynergy, an efficient deterministic overlapping clustering algorithm adapted from a recently developed framework. Mirsynergy operates in two stages: it first forms MiRMs based on co-occurring microRNA (miRNA) targets and then expands each MiRM by greedily including (excluding) mRNAs into (from) the MiRM to maximize the synergy score, which is a function of miRNA-mRNA and gene-gene interactions. Using expression data for ovarian, breast and thyroid cancer from The Cancer Genome Atlas, we compared Mirsynergy with internal controls and existing methods. Mirsynergy-MiRMs exhibit significantly higher functional enrichment and more coherent miRNA-mRNA expression anti-correlation. Based on Kaplan-Meier survival analysis, we proposed several prognostically promising MiRMs and envisioned their utility in cancer research.
  
  
  METHODS
  Mirsynergy is implemented/available as an R/Bioconductor package at www.cs.utoronto.ca/∼yueli/Mirsynergy.html.
authors.affiliation: Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Ka-Chun
authors.initials: KC
authors.lastname: Wong
authors.affiliation: Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada Department of Computer Science, The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada, College of Information Science and Engineering, Hunan University, Changsha, Hunan, 410082, China and Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D004843:Epistasis, Genetic; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger