title: The differential disease regulome.
abstract: BACKGROUND
  Transcription factors in disease-relevant pathways represent potential drug targets, by impacting a distinct set of pathways that may be modulated through gene regulation. The influence of transcription factors is typically studied on a per disease basis, and no current resources provide a global overview of the relations between transcription factors and disease. Furthermore, existing pipelines for related large-scale analysis are tailored for particular sources of input data, and there is a need for generic methodology for integrating complementary sources of genomic information.
  
  
  RESULTS
  We here present a large-scale analysis of multiple diseases versus multiple transcription factors, with a global map of over-and under-representation of 446 transcription factors in 1010 diseases. This map, referred to as the differential disease regulome, provides a first global statistical overview of the complex interrelationships between diseases, genes and controlling elements. The map is visualized using the Google map engine, due to its very large size, and provides a range of detailed information in a dynamic presentation format.The analysis is achieved through a novel methodology that performs a pairwise, genome-wide comparison on the cartesian product of two distinct sets of annotation tracks, e.g. all combinations of one disease and one TF.The methodology was also used to extend with maps using alternative data sets related to transcription and disease, as well as data sets related to Gene Ontology classification and histone modifications. We provide a web-based interface that allows users to generate other custom maps, which could be based on precisely specified subsets of transcription factors and diseases, or, in general, on any categorical genome annotation tracks as they are improved or become available.
  
  
  CONCLUSIONS
  We have created a first resource that provides a global overview of the complex relations between transcription factors and disease. As the accuracy of the disease regulome depends mainly on the quality of the input data, forthcoming ChIP-seq based binding data for many TFs will provide improved maps. We further believe our approach to genome analysis could allow an advance from the current typical situation of one-time integrative efforts to reproducible and upgradable integrative analysis. The differential disease regulome and its associated methodology is available at http://hyperbrowser.uio.no.
authors: Department of Informatics, University of Oslo, Blindern, 0316 Oslo, Norway.
authors: Geir K
authors: GK
authors: Sandve
authors: Sveinung
authors: S
authors: Gundersen
authors: Halfdan
authors: H
authors: Rydbeck
authors: Ingrid K
authors: IK
authors: Glad
authors: Lars
authors: L
authors: Holden
authors: Marit
authors: M
authors: Holden
authors: Knut
authors: K
authors: Liestøl
authors: Trevor
authors: T
authors: Clancy
authors: Finn
authors: F
authors: Drabløs
authors: Egil
authors: E
authors: Ferkingstad
authors: Morten
authors: M
authors: Johansen
authors: Vegard
authors: V
authors: Nygaard
authors: Eivind
authors: E
authors: Tøstesen
authors: Arnoldo
authors: A
authors: Frigessi
authors: Eivind
authors: E
authors: Hovig
mesh_terms: D003196:Computer Graphics; D004194:Disease / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006801:Humans; D020407:Internet; D058977:Molecular Sequence Annotation; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014157:Transcription Factors