Comparison of molecular signatures from multiple skin diseases identifies mechanisms of immunopathogenesis

Megan S. Inkeles, Philip O. Scumpia, William R. Swindell, David Lopez, Rosane M.B. Teles, Thomas G. Graeber, Stephan Meller, Bernhard Homey, James T. Elder, Michel Gilliet, Robert L. Modlin, Matteo Pellegrini

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The ability to obtain gene expression profiles from human disease specimens provides an opportunity to identify relevant gene pathways, but is limited by the absence of data sets spanning a broad range of conditions. Here, we analyzed publicly available microarray data from 16 diverse skin conditions in order to gain insight into disease pathogenesis. Unsupervised hierarchical clustering separated samples by disease as well as common cellular and molecular pathways. Disease-specific signatures were leveraged to build a multi-disease classifier, which predicted the diagnosis of publicly and prospectively collected expression profiles with 93% accuracy. In one sample, the molecular classifier differed from the initial clinical diagnosis and correctly predicted the eventual diagnosis as the clinical presentation evolved. Finally, integration of IFN-regulated gene programs with the skin database revealed a significant inverse correlation between IFN-β and IFN-γ programs across all conditions. Our study provides an integrative approach to the study of gene signatures from multiple skin conditions, elucidating mechanisms of disease pathogenesis. In addition, these studies provide a framework for developing tools for personalized medicine toward the precise prediction, prevention, and treatment of disease on an individual level.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalJournal of Investigative Dermatology
Volume135
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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