title: KDDN: an open-source Cytoscape app for constructing differential dependency networks with significant rewiring.
abstract: We have developed an integrated molecular network learning method, within a well-grounded mathematical framework, to construct differential dependency networks with significant rewiring. This knowledge-fused differential dependency networks (KDDN) method, implemented as a Java Cytoscape app, can be used to optimally integrate prior biological knowledge with measured data to simultaneously construct both common and differential networks, to quantitatively assign model parameters and significant rewiring p-values and to provide user-friendly graphical results. The KDDN algorithm is computationally efficient and provides users with parallel computing capability using ubiquitous multi-core machines. We demonstrate the performance of KDDN on various simulations and real gene expression datasets, and further compare the results with those obtained by the most relevant peer methods. The acquired biologically plausible results provide new insights into network rewiring as a mechanistic principle and illustrate KDDN's ability to detect them efficiently and correctly. Although the principal application here involves microarray gene expressions, our methodology can be readily applied to other types of quantitative molecular profiling data.
  
  
  BACKGROUND
  Source code and compiled package are freely available for download at http://apps.cytoscape.org/apps/kddn.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Bai
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xuan
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Herrington
authors.affiliation: Department of Electrical & Computer Engineering, Virginia Tech, Arlington, VA 22203, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 and Department of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D002453:Cell Cycle / Q000235:genetics; D053263:Gene Regulatory Networks; D018816:Genes, cdc / Q000235:genetics*; D008954:Models, Biological; D058977:Molecular Sequence Annotation; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D012984:Software; D049490:Systems Biology / Q000379:methods*