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

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

Research output: Contribution to journalArticle

108 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere44274
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 5 2012
Externally publishedYes

Fingerprint

psoriasis
Transcriptome
Psoriasis
meta-analysis
transcriptome
Meta-Analysis
pathogenesis
Genes
genes
Skin
Microarrays
Methylation
fatty acid metabolism
Experiments
Metabolic Diseases
metabolic syndrome
skin diseases
Pathology
atherosclerosis
Lipid Metabolism

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tian, S., Krueger, J. G., Li, K., Jabbari, A., Brodmerkel, C., Lowes, M. A., & Suárez-Fariñas, M. (2012). Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the "Core" Pathogenesis of Disease. PLoS One, 7(9), [e44274]. https://doi.org/10.1371/journal.pone.0044274

Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the "Core" Pathogenesis of Disease. / Tian, Suyan; Krueger, James G.; Li, Katherine; Jabbari, Ali; Brodmerkel, Carrie; Lowes, Michelle A.; Suárez-Fariñas, Mayte.

In: PLoS One, Vol. 7, No. 9, e44274, 05.09.2012.

Research output: Contribution to journalArticle

Tian, S, Krueger, JG, Li, K, Jabbari, A, Brodmerkel, C, Lowes, MA & Suárez-Fariñas, M 2012, 'Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the "Core" Pathogenesis of Disease', PLoS One, vol. 7, no. 9, e44274. https://doi.org/10.1371/journal.pone.0044274
Tian, Suyan ; Krueger, James G. ; Li, Katherine ; Jabbari, Ali ; Brodmerkel, Carrie ; Lowes, Michelle A. ; Suárez-Fariñas, Mayte. / Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the "Core" Pathogenesis of Disease. In: PLoS One. 2012 ; Vol. 7, No. 9.
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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.",
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