Additional file 1:

Differentially expressed genes between ALS cases and controls. Standard differential expression analysis that reports genes that are differentially expressed between ALS and healthy controls in the discovery set. At a false discovery rate cut-off of 0.05, 2300 probes were differentially expressed between ALS cases and controls.

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Additional file 2:

Reproducibility of co-expression modules across three data sets. Robustness of module detection across three networks denoted by R1, R2, and R3 corresponding to data sets 1, 2, and 3, respectively. Genes are colored according to their module assignment in the discovery set (R1) where five distinct branches (modules) were found (colored in Blue, Green, Red, Turquoise and Yellow). The fact that most genes of the same color tend to cluster together in data sets R2 and R3 reflects that these modules can also be found in these test data sets. The ALS related modules (Blue and Yellow) are preserved across all three data sets but the Red and Green module can only be found in data sets R1 and R2. An alternatively way of studying module preservation is afforded by module membership measures, see Additional File 3.

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Additional file 3:

Scatterplots of module membership measures between the three data sets. Genes are colored by their module assignment in the discovery set. The axes correspond to module membership measures in the different data sets. MMBlueR1, MMBlueR2, MMBlueR3 denotes the module membership with regard to the Blue module in data sets 1, 2, and 3, respectively. Note that genes with high positive (or high negative) Blue module membership in data set 1 tend to have a similar value in data sets 2 and 3. The same applies for module membership with regard to the Yellow module. Also note that the Blue genes tend to have negative module membership values with regard to the yellow module and vice versa. This reflects the fact that the Blue and Yellow module eigengenes are anti-correlated. The fact that the Blue and Yellow module membership values are preserved across the three data sets reflects the fact that these modules can be detected in all three data sets (Additional File 2).

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Additional file 4:

Module membership annotation table. The table provides the module membership annotation with regard to different modules in each of the 3 independent data sets. Values are reported for the 15463 probes for which there was significant evidence of presence in blood. MMBlueR1 denotes the module membership value to the Blue module in data set 1, i.e. the correlation between expression profiles and the Blue module eigengene. PvalueMMblueR1 denotes the corresponding correlation test p-value. The mean module membership with regard to the Blue module is referred to as MeanMMblue.

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Additional file 5:

Comprehensive functional enrichment results of an Ingenuity Pathways Analysis. The figure shows the functional enrichment results of an Ingenuity Pathways Analysis for four different gene lists comprised of 500 genes each. Specifically, functional enrichment is reported for 500 genes with highest membership to the Blue Module (blue horizontal bars), highest membership to the Yellow Module (yellow bars), lowest WGCNA gene selection score p.weighted (turquoise bars), and most significant Student T-test (black bars).

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Additional file 6:

Selected functional enrichment results of an Ingenuity Pathways Analysis. This figure represents a selected view of Additional File 5. Ingenuity Pathways Analysis shows selected overrepresented categories in the 3 network related lists comprised of 500 genes each. Specifically, functional enrichment is reported for 500 genes with highest membership to the Blue Module, the Yellow Module, and most significant WGCNA gene selection score (p.weighted).

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Additional file 7:

Results of an Ingenuity biomarker analysis. This Excel file reports the results of an Ingenuity biomarker analysis where we analyzed the top 500 genes with most significant WGCNA score (p.weighted). The table reports in which tissues matching genes are known to be expressed and known drug targets for matching genes.

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Additional file 8:

Intramodular hub genes in the ALS related co-expression modules. The table reports hub genes in the Blue and Yellow module with possible function in pathogenesis in ALS based on Gene Ontology function. Selection was made within the top 100 most highly connected genes in both modules and genes were categorized by their Gene Ontology (GO) function. Module membership is listed as well as fold change, Area Under the ROC Curve (AUC), sensitivity (Sensit), Specificity (Specif) and overall p-value of differential expression.

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