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Meta-analysis derived (MAD) transcriptome of psoriasis defines the 'core' pathogenesis of disease
- Source :
- PLoS ONE, Vol 7, Iss 9, p e44274 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
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.
- Subjects :
- Skin Physiology
Anatomy and Physiology
Microarray
Microarrays
Dermatologic Pathology
Transcriptome
0302 clinical medicine
Skin
Oligonucleotide Array Sequence Analysis
Genetics
0303 health sciences
Multidisciplinary
Statistics
3. Good health
030220 oncology & carcinogenesis
Medicine
DNA microarray
Algorithms
Research Article
Signal Transduction
Clinical Research Design
Inflammatory Diseases
Science
Dermatology
Biostatistics
Biology
Autoimmune Diseases
03 medical and health sciences
Psoriasis
medicine
Humans
Gene
030304 developmental biology
Inflammation
Models, Statistical
Models, Genetic
Microarray analysis techniques
Gene Expression Profiling
Computational Biology
Lipid Metabolism
medicine.disease
Gene expression profiling
Genomic Profile
Clinical Immunology
Meta-Analyses
Mathematics
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....5bc275b55cc9eca342d71c98a16009fb