title: Network-based analysis of omics data: the LEAN method.
abstract: Most computational approaches for the analysis of omics data in the context of interaction networks have very long running times, provide single or partial, often heuristic, solutions and/or contain user-tuneable parameters.
  
  
  
  We introduce local enrichment analysis (LEAN) for the identification of dysregulated subnetworks from genome-wide omics datasets. By substituting the common subnetwork model with a simpler local subnetwork model, LEAN allows exact, parameter-free, efficient and exhaustive identification of local subnetworks that are statistically dysregulated, and directly implicates single genes for follow-up experiments.
  
  
  
  Evaluation on simulated and biological data suggests that LEAN generally detects dysregulated subnetworks better, and reflects biological similarity between experiments more clearly than standard approaches. A strong signal for the local subnetwork around Von Willebrand Factor (VWF), a gene which showed no change on the mRNA level, was identified by LEAN in transcriptome data in the context of the genetic disease Cerebral Cavernous Malformations (CCM). This signal was experimentally found to correspond to an unexpected strong cellular effect on the VWF protein. LEAN can be used to pinpoint statistically significant local subnetworks in any genome-scale dataset.
  
  
  
  The R-package LEANR implementing LEAN is supplied as supplementary material and available on CRAN ( https://cran.r-project.org ).
  
  
  
  benno@pasteur.fr or tournier-lasserve@univ-paris-diderot.fr.
  
  
  
  Supplementary data are available at Bioinformatics online.
authors: Univ Paris Diderot, Sorbonne Paris Cité, UMRS 1161, F-75010 Paris, France.|INSERM, U1161, F-75010 Paris, France.
authors: Frederik
authors: F
authors: Gwinner
authors: Univ Paris Diderot, Sorbonne Paris Cité, UMRS 1161, F-75010 Paris, France.|INSERM, U1161, F-75010 Paris, France.
authors: Gwénola
authors: G
authors: Boulday
authors: Univ Paris Diderot, Sorbonne Paris Cité, UMRS 958, F-75010 Paris, France.|INSERM, U958, F-75010 Paris, France.
authors: Claire
authors: C
authors: Vandiedonck
authors: Univ Paris Diderot, Sorbonne Paris Cité, UMRS 1161, F-75010 Paris, France.|INSERM, U1161, F-75010 Paris, France.
authors: Minh
authors: M
authors: Arnould
authors: Univ Paris Diderot, Sorbonne Paris Cité, UMRS 1161, F-75010 Paris, France.|INSERM, U1161, F-75010 Paris, France.
authors: Cécile
authors: C
authors: Cardoso
authors: Systems Biology Lab, C3BI, USR 3756, Institut Pasteur/CNRS, Institut Pasteur, F-75015 Paris, France.|Functional Genetics of Infectious Diseases Unit, Institut Pasteur, F-75015 Paris, France.|Univ Paris-Descartes, Sorbonne Paris Cité, F-75006 Paris, France.
authors: Iryna
authors: I
authors: Nikolayeva
authors: Systems Biology Lab, C3BI, USR 3756, Institut Pasteur/CNRS, Institut Pasteur, F-75015 Paris, France.
authors: Oriol
authors: O
authors: Guitart-Pla
authors: Unité 1176, INSERM, Univ Paris-Sud, Université Paris-Saclay, F-94270 Le Kremlin-Bicêtre, France.
authors: Cécile V
authors: CV
authors: Denis
authors: Unité 1176, INSERM, Univ Paris-Sud, Université Paris-Saclay, F-94270 Le Kremlin-Bicêtre, France.
authors: Olivier D
authors: OD
authors: Christophe
authors: Functional Genetics of Infectious Diseases Unit, Institut Pasteur, F-75015 Paris, France.|Genetics and Genomics of Insect Vectors, Institut Pasteur, F-75015 Paris, France.
authors: Johann
authors: J
authors: Beghain
authors: Univ Paris Diderot, Sorbonne Paris Cité, UMRS 1161, F-75010 Paris, France.|INSERM, U1161, F-75010 Paris, France.|AP-HP, Groupe Hospitalier Saint-Louis Lariboisière-Fernand-Widal, F-75010 Paris, France.
authors: Elisabeth
authors: E
authors: Tournier-Lasserve
authors: Systems Biology Lab, C3BI, USR 3756, Institut Pasteur/CNRS, Institut Pasteur, F-75015 Paris, France.
authors: Benno
authors: B
authors: Schwikowski
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D011506:Proteins / Q000235:genetics; D012984:Software; D059467:Transcriptome; D014841:von Willebrand Factor / Q000235:genetics
chemical_list: D011506:Proteins; D014841:von Willebrand Factor