Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease.
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...
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oai:doaj.org-article:9857b6917b064f50a74d1fe679c629362021-11-18T07:06:34ZMeta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease.1932-620310.1371/journal.pone.0044274https://doaj.org/article/9857b6917b064f50a74d1fe679c629362012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22957057/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Suyan TianJames G KruegerKatherine LiAli JabbariCarrie BrodmerkelMichelle A LowesMayte Suárez-FariñasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44274 (2012) |
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Medicine R Science Q Suyan Tian James G Krueger Katherine Li Ali Jabbari Carrie Brodmerkel Michelle A Lowes Mayte Suárez-Fariñas Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease. |
description |
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. |
format |
article |
author |
Suyan Tian James G Krueger Katherine Li Ali Jabbari Carrie Brodmerkel Michelle A Lowes Mayte Suárez-Fariñas |
author_facet |
Suyan Tian James G Krueger Katherine Li Ali Jabbari Carrie Brodmerkel Michelle A Lowes Mayte Suárez-Fariñas |
author_sort |
Suyan Tian |
title |
Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease. |
title_short |
Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease. |
title_full |
Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease. |
title_fullStr |
Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease. |
title_full_unstemmed |
Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease. |
title_sort |
meta-analysis derived (mad) transcriptome of psoriasis defines the "core" pathogenesis of disease. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/9857b6917b064f50a74d1fe679c62936 |
work_keys_str_mv |
AT suyantian metaanalysisderivedmadtranscriptomeofpsoriasisdefinesthecorepathogenesisofdisease AT jamesgkrueger metaanalysisderivedmadtranscriptomeofpsoriasisdefinesthecorepathogenesisofdisease AT katherineli metaanalysisderivedmadtranscriptomeofpsoriasisdefinesthecorepathogenesisofdisease AT alijabbari metaanalysisderivedmadtranscriptomeofpsoriasisdefinesthecorepathogenesisofdisease AT carriebrodmerkel metaanalysisderivedmadtranscriptomeofpsoriasisdefinesthecorepathogenesisofdisease AT michellealowes metaanalysisderivedmadtranscriptomeofpsoriasisdefinesthecorepathogenesisofdisease AT maytesuarezfarinas metaanalysisderivedmadtranscriptomeofpsoriasisdefinesthecorepathogenesisofdisease |
_version_ |
1718423929847021568 |