{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:03:59Z","timestamp":1766066639013,"version":"3.37.3"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T00:00:00Z","timestamp":1482278400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European consortium ERA-net NEURON","award":["ANR-10-LABX-62-IBEID"],"award-info":[{"award-number":["ANR-10-LABX-62-IBEID"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["P41 GM103504"],"award-info":[{"award-number":["P41 GM103504"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>The R-package LEANR implementing LEAN is supplied as supplementary material and available on CRAN (https:\/\/cran.r-project.org).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btw676","type":"journal-article","created":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T19:06:25Z","timestamp":1477422385000},"page":"701-709","source":"Crossref","is-referenced-by-count":20,"title":["Network-based analysis of omics data: the LEAN method"],"prefix":"10.1093","volume":"33","author":[{"given":"Frederik","family":"Gwinner","sequence":"first","affiliation":[{"name":"Univ Paris Diderot, Sorbonne Paris Cit\u00e9, UMRS 1161, Paris, France"},{"name":"INSERM, U1161, Paris, France"}]},{"given":"Gw\u00e9nola","family":"Boulday","sequence":"additional","affiliation":[{"name":"Univ Paris Diderot, Sorbonne Paris Cit\u00e9, UMRS 1161, Paris, France"},{"name":"INSERM, U1161, Paris, France"}]},{"given":"Claire","family":"Vandiedonck","sequence":"additional","affiliation":[{"name":"Univ Paris Diderot, Sorbonne Paris Cit\u00e9, UMRS 958, Paris, France"},{"name":"INSERM, U958, Paris, France"}]},{"given":"Minh","family":"Arnould","sequence":"additional","affiliation":[{"name":"Univ Paris Diderot, Sorbonne Paris Cit\u00e9, UMRS 1161, Paris, France"},{"name":"INSERM, U1161, Paris, France"}]},{"given":"C\u00e9cile","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Univ Paris Diderot, Sorbonne Paris Cit\u00e9, UMRS 1161, Paris, France"},{"name":"INSERM, U1161, Paris, France"}]},{"given":"Iryna","family":"Nikolayeva","sequence":"additional","affiliation":[{"name":"Systems Biology Lab, C3BI, USR 3756, Institut Pasteur\/CNRS, Institut Pasteur, Paris, France"},{"name":"Functional Genetics of Infectious Diseases Unit, Institut Pasteur, Paris, France"},{"name":"Univ Paris-Descartes, Sorbonne Paris Cit\u00e9, Paris, France"}]},{"given":"Oriol","family":"Guitart-Pla","sequence":"additional","affiliation":[{"name":"Systems Biology Lab, C3BI, USR 3756, Institut Pasteur\/CNRS, Institut Pasteur, Paris, France"}]},{"given":"C\u00e9cile V","family":"Denis","sequence":"additional","affiliation":[{"name":"Unit\u00e9 1176, INSERM, Univ Paris-Sud, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}]},{"given":"Olivier D","family":"Christophe","sequence":"additional","affiliation":[{"name":"Unit\u00e9 1176, INSERM, Univ Paris-Sud, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}]},{"given":"Johann","family":"Beghain","sequence":"additional","affiliation":[{"name":"Functional Genetics of Infectious Diseases Unit, Institut Pasteur, Paris, France"},{"name":"Genetics and Genomics of Insect Vectors, Institut Pasteur, Paris, France"}]},{"given":"Elisabeth","family":"Tournier-Lasserve","sequence":"additional","affiliation":[{"name":"Univ Paris Diderot, Sorbonne Paris Cit\u00e9, UMRS 1161, Paris, France"},{"name":"INSERM, U1161, Paris, France"},{"name":"AP-HP, Groupe Hospitalier Saint-Louis Lariboisi\u00e8re-Fernand-Widal, Paris, France"}]},{"given":"Benno","family":"Schwikowski","sequence":"additional","affiliation":[{"name":"Systems Biology Lab, C3BI, USR 3756, Institut Pasteur\/CNRS, Institut Pasteur, Paris, France"}]}],"member":"286","published-online":{"date-parts":[[2016,12,6]]},"reference":[{"key":"2023020204505425100_btw676-B1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-immunol-040210-092915","article-title":"Integration of genetic and immunological insights into a model of celiac disease pathogenesis","volume":"29","author":"Abadie","year":"2011","journal-title":"Annu. 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