title: Tissue Specificity of Human Disease Module.
abstract: Genes carrying mutations associated with genetic diseases are present in all human cells; yet, clinical manifestations of genetic diseases are usually highly tissue-specific. Although some disease genes are expressed only in selected tissues, the expression patterns of disease genes alone cannot explain the observed tissue specificity of human diseases. Here we hypothesize that for a disease to manifest itself in a particular tissue, a whole functional subnetwork of genes (disease module) needs to be expressed in that tissue. Driven by this hypothesis, we conducted a systematic study of the expression patterns of disease genes within the human interactome. We find that genes expressed in a specific tissue tend to be localized in the same neighborhood of the interactome. By contrast, genes expressed in different tissues are segregated in distinct network neighborhoods. Most important, we show that it is the integrity and the completeness of the expression of the disease module that determines disease manifestation in selected tissues. This approach allows us to construct a disease-tissue network that confirms known and predicts unexpected disease-tissue associations.
authors.affiliation: Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA.|Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., 02215 Boston, USA.
authors.forename: Maksim
authors.initials: M
authors.lastname: Kitsak
authors.affiliation: Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA.|Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., 02215 Boston, USA.|Channing Division of Network Medicine, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA.|Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., 02215 Boston, USA.|Center for Network Science, Central European University, Nador u. 9, 1051 Budapest, Hungary.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, A-1090 Vienna, Austria.
authors.forename: Jörg
authors.initials: J
authors.lastname: Menche
authors.affiliation: Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA.|Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., 02215 Boston, USA.|Institute for Research in Biomedicine, Carrer de Baldiri Reixac, 08028 Barcelona, Spain.
authors.forename: Emre
authors.initials: E
authors.lastname: Guney
authors.affiliation: Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA.|Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., 02215 Boston, USA.|DZZOM Inc., 111 Huntington Avenue, Boston, MA 02119, USA.
authors.forename: Susan Dina
authors.initials: SD
authors.lastname: Ghiassian
authors.affiliation: Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.affiliation: Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA.|Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., 02215 Boston, USA.|Center for Network Science, Central European University, Nador u. 9, 1051 Budapest, Hungary.|DZZOM Inc., 111 Huntington Avenue, Boston, MA 02119, USA.|Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.|Department of Theoretical Physics, Budapest University of Technology and Economics, H1111, Budapest, Hungary.
authors.forename: Albert-László
authors.initials: AL
authors.lastname: Barabási
mesh_terms: D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007031:Hypothalamus / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D015233:Models, Statistical; D009154:Mutation; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000378:metabolism; D025941:Protein Interaction Mapping; D014018:Tissue Distribution; D059467:Transcriptome