Genes in consensus networks of the DR3/DR4, DR4/DR4 and DR4/DRX groups.

<p>GO terms on biological process and molecular function from <a href="http://www.geneontology.org" target="_blank">www.geneontology.org</a>.</p><p>Abbreviations: ATP, adenosine triphosphate.</p

Consensus networks.

<p><b>A</b>) displays the consensus network for the DR3/DR3 and the DR3/DRX risk groups. <b>B</b>) displays the consensus network for the DR3/DR4 and the DR4/DRX risk group. <b>C</b>) displays the consensus network for the DR4/DR4 risk group. Proteins encoded from genes in the HLA region are shown in red.</p

P-value distribution for HLA specific networks and the reference group.

<p><b>A</b>) DR3/DR3: most extreme deviation higher D = 0.2083, p<0.001. <b>B</b>) DR3/DRX: most extreme deviation higher D = 0.3347, p<0.001. <b>C</b>) DR3/DR4: most extreme deviation lower D = 0.2890, p<0.001. <b>D</b>) DR4/DR4: most extreme deviation lower D = 0.4772, p<0.001. <b>E</b>) DR4/DRX: most extreme deviation lower D = 0.1586, p<0.001. <b>F</b>) DRX/DRX: most extreme deviation lower D = 0.3199, p<0.001. Dashed line: HLA risk group, solid line: reference group.</p

The top significant networks modules identified for each HLA risk group.

a)<p>Bait specifies the protein that was used to capture each network.</p>b)<p>The p-value after permutation for each HLA risk group.</p>c)<p>The p-value without HLA risk group stratification as a reference.</p>d)<p>The p-value for each protein network after correction with the reference.</p

Summarization of the genes occurring most frequently in the network modules for each HLA risk group.

<p>Summarization of the genes occurring most frequently in the network modules for each HLA risk group.</p

Genes in consensus network of the DR3/DR3 and DR3/DRX groups.

<p>GO terms on biological process and molecular function from <a href="http://www.geneontology.org" target="_blank">www.geneontology.org</a>.</p><p>Abbreviations: IL, interleukin; LPS, lipopolysaccharide; NF-κB, nuclear factor-kappa beta; STAT1, signal transduction and activator of transcription 1; MAPK, mitogen-activated protein kinase; MIP-1α, macrophage inflammatory protein-1α; MCP-1, monocyte chemoattractant protein-1; SLE, systemic lupus erythematosus; TGF-β, transforming growth factor-β; HDAC, histone deacteylase; NO, nitric oxide; INS, insulinoma.</p

Overview of the developed approach.

<p><b>A</b>) Genes located in the HLA region were identified and <b>B</b>) mapped to nodes or proteins in a 2^nd order network in the InWeb. <b>C</b>) HLA proteins and their interaction partners were used as bait to produce virtual pull-downs of network modules. <b>D</b>) Identified network modules were reduced to only contain proteins from the HLA region, as these could be associated to signals from the TDT analysis. <b>E</b>) SNPs from the TDT analysis were mapped to genes + 2000 bp up- and downstream the transcription start and stop site respectively. The best SNP signal for each gene was then mapped to the corresponding proteins in the network modules.</p

Overview of predicted interactions in network A.

<p>Protein-protein interactions in this network originates from predicted genetic interactions between the HLA-region on chromosome 6 (<i>BAT1, ITPR3, RPS18</i> and <i>TUBB</i>) and chromosomal regions on chromosome 2 (around <i>D2S177, HNRPL</i>), chromosome 13 (<i>D13S170, LMO7</i>), chromosome 4 (<i>D4S403, WDR1</i>) and chromosome 16 (<i>D16S287, RPS15A</i>), respectively. The <i>ELF5</i> gene is positioned on chromosome 11. Red arrows and corresponding plots refer to four genes that were demonstrated significantly down-regulated in human pancreatic islets upon cytokine-stimulation. In the plots nodes to the left represent expression levels for all nine donors in un-stimulated condition, whereas nodes to the right represent cytokine-stimulated expression levels.</p

Protein-protein interactions in network B, originating from predicted genetic interactions between the HLA region on chromosome 6 (<i>RDBP</i> and <i>GTF2H4</i>) and chromosomal regions on chromosome 16 (<i>D16S287, RRN3</i> and <i>ERCC4)</i>) and chromosome 1 (<i>D1S229, TAF1A</i>).

<p>The <i>TAF1A</i> gene demonstrated significantly higher expression in lymphocytes from T1D patients compared to lymphocytes from control individuals. The <i>TYW3</i> and <i>GUF1</i> are positioned on chromosome 1p31.1 and 4p13, respectively.</p

Metabolic effect and oral glucose test after anti-IL20 treatment.

<p>One week post last treatment with anti-IL-20, the mice was terminated. During the experiment and at time of termination HbA1c (A), blood glucose (B) and weight (C) was determined. Oral glucose evaluation was conducted one day before termination of the experiment (D). Area under the curve oral glucose test was calculated (E). Plasma level of insulin was measured during the oral glucose tolerance test (F). Each group contained 12 animals. Statistical evaluation comparing the start value in each group with the termination value as well as the termination value between the groups was performed with one way ANOVA in A-C. Linear regression analysis was performed to determine if the two groups showed a difference in the slope of the parameter evaluated during the time of the experiment A-C. Student’s T-test was used to determine statistical significance in E.</p