Figure 1.
PRIMA diagram and study schema.
A. PRIMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram. B. Schema describing the steps taken during the meta-analysis. N and P represent the number of samples (N) and patients (P) respectively in each study.
Figure 2.
Overview of the MAD-5 and MAD-3 transcriptomes.
A. Venn diagram showing that when comparing the MAD-5 transcriptome with the intersection of DEGs identified by individual studies, the meta-analysis always identified a much larger set. B. Venn diagram showing the same comparison as A but for MAD-3 transcriptome. C. 3D Barplots showing the overlap of MAD-5 genes (blue bars) by the number of individual studies (x-axis). For example: among the MAD-5 transcriptome, 347 genes were identified by 4 studies and 100 by all 5 studies. For comparison the numbers for the set of genes that were identified by any of the individual studies (Union) is also represented (red bars). Most DEGs from the meta-analysis appeared in at least two of these studies. Integration Discovery Genes (IDD) represents the set of genes only identified by the meta-analysis. D. 3D Barplots showing the same comparison as C for MAD-3. E. Color-coded graphs showing the comparison of MADs transcriptomes and individual studies. Each row represents a gene and the color indicates whether the gene is up-regulated (red), down-regulated (green) or not differentially expressed (gray) in each (columns) and the meta-analysis. Meta: meta-analysis; S-F+: Suarez-Farinas 2012, hgu33plus2 chips; G: Gudjonsson’2009; S-F: Suarez-Farinas’2010; R: Reischl’2007; Y: Yao’2008.
Table 1.
Top 25 Up and Down-regulated genes in the MAD-3 transcriptome.
Figure 3.
Comparison with other transcriptomes.
A. Cutaneous localization of MAD-5 transcriptome. 49% of MAD-5 genes (black rectangle) were identified as being part of the Epidermis (green rectangle) or Dermis (yellow rectangle) psoriasis transcriptome defined by the use of laser capture micro-dissection (LCM) techniques (using the same cutoffs FDR<0.05 and FCH>2). Genes identified in both Epidermis and Dermis transcriptomes are in the blue rectangle. B. Venn-Diagram showing the intersection between the MAD-3 psoriasis transcriptome and RNA-seq pilot experiment (using the same cutoffs FDR<0.05 and FCH>2). Numbers are colored in red and green to represent up-regulated or down-regulated genes respectively. The gray zone represents genes identified by RNA-seq but that were not physically present in the hgu133plus2 chips.
Figure 4.
Comparison of canonical pathways overrepresented in MAD-3 transcriptome (blue bars) and Suarez-Farinas+ (red bars), which is the study with the largest sample size and number of DEG. Bars represents a –log10 transformation of the Benjamini-Hochberg adjusted p-value, which controls FDR. Only pathways with FDR<0.1 (which corresponds to 1 in the –log10 scale; represented by yellow line) in either MAD-3 or Suarez-Farinas+ are shown.
Table 2.
Integration-Driven Discovery (IDD) genes in the MAD-3 transcriptome.
Table 3.
RT-PCR validation on IDD genes.
Figure 5.
Radviz plots showing how the 20 genes selected by MTGDR procedure separate the lesional (LS) and non-lesional (NL) samples apart in each study. Perfect separation between LS and NL samples can be seen in every study. S-F+: Suarez-Farinas 2012, hgu33plus2 chips; G: Gudhjonsson’2009; S-F: Suarez-Farinas’2010; R: Reischl’2007; Y: Yao’2008. Center insert shows biological relevance of these genes. Top 25 psoriasis genes in Table 1 are underline. 6 of these 20 genes have been identified as top methylation genes discriminating between psoriasis (LS) and healthy skin. 4/20 were identified as part of the Residual Disease Genomic Profile (RGDP) or “Molecular Scar”.