Figure 1.
The network derived from the 35 genes which composed the IFN signature using Ingenuity Pathway Analysis (IPA) software.
Edges (gene relationships) are displayed with labels that describe the nature of the relationship between nodes (genes). Nodes are displayed using various shapes that represent the functional class of the gene product. Genes in red belong to the list of the 35 IFN-related genes. Genes in blue were integrated into the computationally generated networks on the basis of the evidence stored in the IPA knowledge memory indicating a relevance to this network. The network showed central connection represented by the type I interferon. The pink arrows represent the direct and indirect interactions for genes of type I family of interferons (IFN-α, IFN-β).
Figure 2.
Gene expression profiles from the IFN signature.
Unsupervised hierarchical clustering of 35 IFN-related genes that distinguish rheumatoid arthritis (RA) patients IFNhigh (blue dendrogram) from RA patients IFNlow (purple dendrogram). Each row represents a gene; each column shows the expression for 35 IFN-related genes expressed by each patients. Red indicates genes that are expressed at higher levels and green indicates genes that are expressed at lower levels.
Figure 3.
Stratification of individuals according to the IFN signature.
Each point represents a single individual with the decision variable calculated from the Classification Algorithm based on a Biological Signature (CABS). The shaded box indicates the normal range according to the rule of the CABS: If Dhigh_low≥1, the signature is defined as “high signature” and If Dhigh_low<1, the signature is defined as “low signature” knowing that Dhigh_low = CORhigh/CORlow.
Figure 4.
Correlation profiles from the different groups.
A correlation index was defined for each gene of the IFN signature as the median of its correlations with the remaining genes. Thus, the correlation profiles for the different groups: healthy controls (HC) IFNlow (blue dotted), HC IFNhigh (blue line), rheumatoid arthritis patients (RA) IFNlow (red dotted) and RA IFNhigh (red line) and systemic lupus erythematosus patients (SLE) IFNhigh (green line), are represented using the 35 calculated correlation indexes from the IFN signature genes. The median values of the correlation indexes obtained for the different groups are 0.27, 0.44, 0.33, 0.63 and 0.68, respectively.
Figure 5.
Comparative analysis of characterization methods of IFN signature.
Each dot represents a single individual. The y-axis represents the decision variable of the IFN signature calculated from CABS. The grey dotted line indicates the threshold according to the rule of the CABS: If Dhigh_low≥1, the signature is defined as “high signature” and If Dhigh_low<1, the signature is defined as “low signature” knowing that Dhigh_low = CORhigh/CORlow. The x-axis represents the average values of gene expression of the IFN signature. The solid grey line indicates the threshold of IFN response, by calculating the 95% limits of the HC (normal values, defined as the mean (SD) expression of the 35 IFN-related genes, ±1.96 SD). If the average gene expression is ≥9.68, the signature is defined as “high signature” and if average gene expression ratio is <9.68, the signature is defined as “low signature”. The shaded boxes show the divergence observed between both methods. The black triangles represent individuals with high average values of gene expression and low decision variable. The black squares represent individuals with low average values of gene expression and high decision variable.
Figure 6.
Follow-up the IFN signature in patients with rheumatoid arthritis (RA) treated with anti-TNF.
Each point represents a single individual with the decision variable calculated from the Classification Algorithm based on a Biological Signature (CABS). The shaded box indicates the normal range according to the rule of the CABS: If Dhigh_low≥1, the signature is defined as “high signature” and If Dhigh_low<1, the signature is defined as “low signature” knowing that Dhigh_low = CORhigh/CORlow. The Wilcoxon signed rank test was used to evaluate the statistical significance between patients before and after anti-TNF treatment A) (*p = 0.0186) B) (**p = 0.002).
Table 1.
Demographic and clinical characteristics of the patients and control subjects.