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Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the “Core” Pathogenesis of Disease

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  • Suyan Tian
  • James G Krueger
  • Katherine Li
  • Ali Jabbari
  • Carrie Brodmerkel
  • Michelle A Lowes
  • Mayte Suárez-Fariñas

Abstract

The cause of psoriasis, a common chronic inflammatory skin disease, is not fully understood. Microarray experiments have been widely used in recent years to identify genes associated with psoriasis pathology, by comparing expression levels of lesional (LS) with adjacent non-lesional (NL) skin. It is commonly observed that the differentially expressed genes (DEGs) differ greatly across experiments, due to variations introduced in the microarray experiment pipeline. Therefore, a statistically based meta-analytic approach, which combines the results of individual studies, is warranted. In this study, a meta-analysis was conducted on 5 microarray data sets, including 193 LS and NL pairs. We termed this the Meta-Analysis Derived (MAD) transcriptome. In “MAD-5” transcriptome, 677 genes were up-regulated and 443 were down-regulated in LS skin compared to NL skin. This represents a much larger set than the intersection of DEGs of these 5 studies, which consisted of 100 DEGs. We also analyzed 3 of the studies conducted on the Affymetrix hgu133plus2 chips and found a greater number of DEGs (1084 up- and 748 down-regulated). Top canonical pathways over-represented in the MAD transcriptome include Atherosclerosis Signaling and Fatty Acid Metabolism, while several “new” genes identified are involved in Cardiovascular Development and Lipid Metabolism. These findings highlight the relationship between psoriasis and systemic manifestations such as the metabolic syndrome and cardiovascular disease. Then, the Meta Threshold Gradient Descent Regularization (MTGDR) algorithm was used to select potential markers distinguishing LS and NL skin. The resulting set (20 genes) contained many genes that were part of the residual disease genomic profile (RDGP) or “molecular scar” after successful treatment, and also genes subject to differential methylation in LS tissues. To conclude, this MAD transcriptome yielded a reference list of reliable psoriasis DEGs, and represents a robust pool of candidates for further discovery of pathogenesis and treatment evaluation.

Suggested Citation

  • Suyan Tian & James G Krueger & Katherine Li & Ali Jabbari & Carrie Brodmerkel & Michelle A Lowes & Mayte Suárez-Fariñas, 2012. "Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the “Core” Pathogenesis of Disease," PLOS ONE, Public Library of Science, vol. 7(9), pages 1-15, September.
    • Handle: RePEc:plo:pone00:0044274
    DOI: 10.1371/journal.pone.0044274
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    References listed on IDEAS

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    1. Zhijin Wu & Rafael A. Irizarry & Robert Gentleman & Francisco Martinez-Murillo & Forrest Spencer, 2004. "A Model-Based Background Adjustment for Oligonucleotide Expression Arrays," Journal of the American Statistical Association, American Statistical Association, vol. 99, pages 909-917, December.
    2. Rainer Zenz & Robert Eferl & Lukas Kenner & Lore Florin & Lars Hummerich & Denis Mehic & Harald Scheuch & Peter Angel & Erwin Tschachler & Erwin F. Wagner, 2005. "Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins," Nature, Nature, vol. 437(7057), pages 369-375, September.
    3. Zhijin Wu & Rafael Irizarry & Robert Gentleman & Francisco Martinez Murillo & Forrest Spencer, 2004. "A Model Based Background Adjustment for Oligonucleotide Expression Arrays," Johns Hopkins University Dept. of Biostatistics Working Paper Series 1001, Berkeley Electronic Press.
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    1. Máté Manczinger & Lajos Kemény, 2013. "Novel Factors in the Pathogenesis of Psoriasis and Potential Drug Candidates Are Found with Systems Biology Approach," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-15, November.
    2. Camila Epprecht & Dominique Guegan & Álvaro Veiga & Joel Correa da Rosa, 2017. "Variable selection and forecasting via automated methods for linear models: LASSO/adaLASSO and Autometrics," Post-Print halshs-00917797, HAL.

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