title: Transcriptome classification reveals molecular subtypes in psoriasis.
abstract: BACKGROUND
  Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes.
  
  
  RESULTS
  We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed.
  
  
  CONCLUSIONS
  Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.
authors.affiliation: Centre for Bioinformatics, Department of Informatics, School of Natural and Mathematical Sciences, King's College London, Strand, London WC2R 2LS, UK.
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Ainali
authors.forename: Najl
authors.initials: N
authors.lastname: Valeyev
authors.forename: Gayathri
authors.initials: G
authors.lastname: Perera
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: Johann E
authors.initials: JE
authors.lastname: Gudjonsson
authors.forename: Christos A
authors.initials: CA
authors.lastname: Ouzounis
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
authors.forename: Sophia
authors.initials: S
authors.lastname: Tsoka
mesh_terms: D019295:Computational Biology / Q000379:methods; D003663:Decision Trees; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D011565:Psoriasis / Q000145:classification* / Q000175:diagnosis / Q000235:genetics; D059467:Transcriptome