title: Differential analysis of biological networks.
abstract: BACKGROUND
  In cancer research, the comparison of gene expression or DNA methylation networks inferred from healthy controls and patients can lead to the discovery of biological pathways associated to the disease. As a cancer progresses, its signalling and control networks are subject to some degree of localised re-wiring. Being able to detect disrupted interaction patterns induced by the presence or progression of the disease can lead to the discovery of novel molecular diagnostic and prognostic signatures. Currently there is a lack of scalable statistical procedures for two-network comparisons aimed at detecting localised topological differences.
  
  
  RESULTS
  We propose the dGHD algorithm, a methodology for detecting differential interaction patterns in two-network comparisons. The algorithm relies on a statistic, the Generalised Hamming Distance (GHD), for assessing the degree of topological difference between networks and evaluating its statistical significance. dGHD builds on a non-parametric permutation testing framework but achieves computationally efficiency through an asymptotic normal approximation.
  
  
  CONCLUSIONS
  We show that the GHD is able to detect more subtle topological differences compared to a standard Hamming distance between networks. This results in the dGHD algorithm achieving high performance in simulation studies as measured by sensitivity and specificity. An application to the problem of detecting differential DNA co-methylation subnetworks associated to ovarian cancer demonstrates the potential benefits of the proposed methodology for discovering network-derived biomarkers associated with a trait of interest.
authors.affiliation: Department of Biomedical Engineering, King's College London, London, SE1 7EH, UK. giovanni.montana@kcl.ac.uk.
authors.forename: Da
authors.initials: D
authors.lastname: Ruan
authors.affiliation: Department of Biomedical Engineering, King's College London, London, SE1 7EH, UK. alastair.young@imperial.ac.uk.
authors.forename: Alastair
authors.initials: A
authors.lastname: Young
authors.affiliation: Department of Mathematics, Imperial College London, London, SW7 2AZ, UK. giovanni.montana@kcl.ac.uk.|Department of Biomedical Engineering, King's College London, London, SE1 7EH, UK. giovanni.montana@kcl.ac.uk.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montana
mesh_terms: D000465:Algorithms; D019175:DNA Methylation; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans