Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

Figure 2

Analyses flowchart. The top half of the figure (above the dashed line) shows how the genes with low topological overlap (low TO genes) are selected and then analyzed for association with biological processes and diseases. The bottom half of the figure shows all the comparisons with the protein-protein interaction (PPI) networks. The region PPI network was created using our set of low TO genes as seed nodes. Since there were six regional comparisons, there resulted six region PPI networks. For each of the 6 regional comparisons, a pair of low TO gene modules was created. One low TO gene module contained the low TO genes that had a higher connectivity in a certain region (say R1) and their direct neighbors in the R1-R2 region PPI network and the other low TO gene module contained the low TO genes that had a higher connectivity in the other region (R2) and their direct neighbors in the R1-R2 region PPI network. The Soler-López AD PPI network was reconstructed from the report by Soler-López et al. The low TO genes from our analyses were mapped onto the Soler-López AD PPI network for the creation of the pair of low TO gene modules. The creation of the pair of low TO gene modules was the same as before except that this time the neighbors were selected from the Soler-López AD PPI network.