title: Disease-gene discovery by integration of 3D gene expression and transcription factor binding affinities.
abstract: BACKGROUND
  The computational evaluation of candidate genes for hereditary disorders is a non-trivial task. Several excellent methods for disease-gene prediction have been developed in the past 2 decades, exploiting widely differing data sources to infer disease-relevant functional relationships between candidate genes and disorders. We have shown recently that spatially mapped, i.e. 3D, gene expression data from the mouse brain can be successfully used to prioritize candidate genes for human Mendelian disorders of the central nervous system.
  
  
  RESULTS
  We improved our previous work 2-fold: (i) we demonstrate that condition-independent transcription factor binding affinities of the candidate genes' promoters are relevant for disease-gene prediction and can be integrated with our previous approach to significantly enhance its predictive power; and (ii) we define a novel similarity measure-termed Relative Intensity Overlap-for both 3D gene expression patterns and binding affinity profiles that better exploits their disease-relevant information content. Finally, we present novel disease-gene predictions for eight loci associated with different syndromes of unknown molecular basis that are characterized by mental retardation.
authors.affiliation: Department of Theoretical Bioinformatics, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), University of Heidelberg, Im 69120 Heidelberg, Germany. r.piro@dkfz.de
authors.forename: Rosario M
authors.initials: RM
authors.lastname: Piro
authors.forename: Ivan
authors.initials: I
authors.lastname: Molineris
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Rainer
authors.initials: R
authors.lastname: König
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005796:Genes; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors