title: A comprehensive functional analysis of tissue specificity of human gene expression.
abstract: BACKGROUND
  In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping') genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes, and those unique to or characteristic of particular tissues.
  
  
  RESULTS
  We measured whole genome expression in 31 human tissues, identifying 2374 housekeeping genes expressed in all tissues, and genes uniquely expressed in each tissue. Comprehensive functional analysis showed that the housekeeping set is substantially larger than previously thought, and is enriched with vital processes such as oxidative phosphorylation, ubiquitin-dependent proteolysis, translation and energy metabolism. Network topology of the housekeeping network was characterized by higher connectivity and shorter paths between the proteins than the global network. Ontology enrichment scoring and network topology of tissue-specific genes were consistent with each tissue's function and expression patterns clustered together in accordance with tissue origin. Tissue-specific genes were twice as likely as housekeeping genes to be drug targets, allowing the identification of tissue 'signature networks' that will facilitate the discovery of new therapeutic targets and biomarkers of tissue-targeted diseases.
  
  
  CONCLUSIONS
  A comprehensive functional analysis of housekeeping and tissue-specific genes showed that the biological function of housekeeping and tissue-specific genes was consistent with tissue origin. Network analysis revealed that tissue-specific networks have distinct network properties related to each tissue's function. Tissue 'signature networks' promise to be a rich source of targets and biomarkers for disease treatment and diagnosis.
authors.affiliation: GeneGo, Inc, Renaissance Drive, St, Joseph, MI 49085, USA. zoltan@genego.com
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Dezso
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.forename: Evgeny
authors.initials: E
authors.lastname: Sviridov
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Serebriyskaya
authors.forename: Damir
authors.initials: D
authors.lastname: Dosymbekov
authors.forename: Andrej
authors.initials: A
authors.lastname: Bugrim
authors.forename: Eugene
authors.initials: E
authors.lastname: Rakhmatulin
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Brennan
authors.forename: Alexey
authors.initials: A
authors.lastname: Guryanov
authors.forename: Kelly
authors.initials: K
authors.lastname: Li
authors.forename: Julie
authors.initials: J
authors.lastname: Blake
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Samaha
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nikolskaya
mesh_terms: D016000:Cluster Analysis; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D005796:Genes / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity