Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the “Core” Pathogenesis of Disease
Open Access
- 5 September 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (9), e44274
- https://doi.org/10.1371/journal.pone.0044274
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.Keywords
This publication has 56 references indexed in Scilit:
- Psoriasis and Other Complex Trait Dermatoses: From Loci to Functional PathwaysJournal of Investigative Dermatology, 2012
- A Subset of Methylated CpG Sites Differentiate Psoriatic from Normal SkinJournal of Investigative Dermatology, 2012
- Transcriptional Profiling of Psoriasis Using RNA-seq Reveals Previously Unidentified Differentially Expressed GenesJournal of Investigative Dermatology, 2012
- Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalitiesJournal of Allergy and Clinical Immunology, 2011
- Resolved Psoriasis Lesions Retain Expression of a Subset of Disease-Related GenesJournal of Investigative Dermatology, 2011
- Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasisJournal of Allergy and Clinical Immunology, 2010
- Global Gene Expression Analysis Reveals Evidence for Decreased Lipid Biosynthesis and Increased Innate Immunity in Uninvolved Psoriatic SkinJournal of Investigative Dermatology, 2009
- Meta-analysis of microarray results: challenges, opportunities, and recommendations for standardizationGene, 2007
- Meta-Analysis Combines Affymetrix Microarray Results Across LaboratoriesComparative and Functional Genomics, 2005
- Meta-analysis in clinical trialsControlled Clinical Trials, 1986