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

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

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

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

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

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