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Transcriptome classification reveals molecular subtypes in psoriasis

Ainali, C; Ouzounis, CA; Tsoka, S; Perera, G; Williams, A; Nestle, FO; Valeyev, N; (2012) Transcriptome classification reveals molecular subtypes in psoriasis. BMC Genomics , 13 , Article 472. 10.1186/1471-2164-13-472. Green open access

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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.Conclusion: 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. © 2012 Ainali et al.; licensee BioMed Central Ltd.

Type: Article
Title: Transcriptome classification reveals molecular subtypes in psoriasis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-2164-13-472
Publisher version: http://dx.doi.org/10.1186/1471-2164-13-472
Language: English
Additional information: © 2012 Ainali et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Education
URI: https://discovery.ucl.ac.uk/id/eprint/1424623
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