title: xHeinz: an algorithm for mining cross-species network modules under a flexible conservation model.
abstract: BACKGROUND
  Integrative network analysis methods provide robust interpretations of differential high-throughput molecular profile measurements. They are often used in a biomedical context-to generate novel hypotheses about the underlying cellular processes or to derive biomarkers for classification and subtyping. The underlying molecular profiles are frequently measured and validated on animal or cellular models. Therefore the results are not immediately transferable to human. In particular, this is also the case in a study of the recently discovered interleukin-17 producing helper T cells (Th17), which are fundamental for anti-microbial immunity but also known to contribute to autoimmune diseases.
  
  
  RESULTS
  We propose a mathematical model for finding active subnetwork modules that are conserved between two species. These are sets of genes, one for each species, which (i) induce a connected subnetwork in a species-specific interaction network, (ii) show overall differential behavior and (iii) contain a large number of orthologous genes. We propose a flexible notion of conservation, which turns out to be crucial for the quality of the resulting modules in terms of biological interpretability. We propose an algorithm that finds provably optimal or near-optimal conserved active modules in our model. We apply our algorithm to understand the mechanisms underlying Th17 T cell differentiation in both mouse and human. As a main biological result, we find that the key regulation of Th17 differentiation is conserved between human and mouse.
  
  
  METHODS
  xHeinz, an implementation of our algorithm, as well as all input data and results, are available at http://software.cwi.nl/xheinz and as a Galaxy service at http://services.cbib.u-bordeaux2.fr/galaxy in CBiB Tools.
  
  
  BACKGROUND
  gunnar.klau@cwi.nl
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Life Sciences, Centrum Wiskunde & Informatica (CWI), Amsterdam, The Netherlands, Centre for Integrative Bioinformatics VU, VU University Amsterdam, The Netherlands, Center for Computational Molecular Biology, Brown University, Providence, RI, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El-Kebir
authors.affiliation: Computational Cancer Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Hayssam
authors.initials: H
authors.lastname: Soueidan
authors.affiliation: Univ. Bordeaux, CBiB, 33000 Bordeaux, France, Univ. Bordeaux, CNRS/LaBRI, 33405 Talence, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hume
authors.affiliation: Genome Informatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen.
authors.forename: Daniela
authors.initials: D
authors.lastname: Beisser
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany, Institute of Human Genetics, University of Würzburg, Würzburg, Germany and.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dittrich
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.affiliation: Univ. Bordeaux, CNRS/LaBRI, 33405 Talence, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Blin
authors.affiliation: Centre for Integrative Bioinformatics VU, VU University Amsterdam, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Heringa
authors.affiliation: Univ. Bordeaux, CBiB, 33000 Bordeaux, France, Univ. Bordeaux, CNRS/LaBRI, 33405 Talence, France.
authors.forename: Macha
authors.initials: M
authors.lastname: Nikolski
authors.affiliation: Computational Cancer Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
authors.affiliation: Life Sciences, Centrum Wiskunde & Informatica (CWI), Amsterdam, The Netherlands, Centre for Integrative Bioinformatics VU, VU University Amsterdam, The Netherlands, Erable Team, INRIA, Lyon, France.
authors.forename: Gunnar W
authors.initials: GW
authors.lastname: Klau
mesh_terms: D000465:Algorithms; D000818:Animals; D057225:Data Mining; D020869:Gene Expression Profiling; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008954:Models, Biological; D060066:Protein Interaction Maps; D013045:Species Specificity; D058504:Th17 Cells / Q000166:cytology