analytically detect and quantify this network reorganization across the demented and non-demented states, we developed a metric we refer to as modular differential connectivity (MDC) (Extended Experimental Procedures). MDC is the ratio of the average connectivity for any pair of module sharing genes in LOAD compared to that of the same genes in the non-demented state, and is a continuous measure ranging from 0 to infinity. This module-centric measure of differential connectivity between the two states is therefore fundamentally different from the gene-centric analysis of previous studies that applied hard cutoffs (Mani et al., 2008). Given the nature of the co-expression network analysis, MDC > 1 indicates gain of connectivity (GOC) or enhanced co-regulation between genes, while MDC < 1 indicates loss of connectivity (LOC) or reduced co-regulation between genes. In extreme cases where MDC >>1, e.g. the glutathione transferase (GST) module (Figure 3B), or MDC <<1, e.g. the nerve myelination module (Figure 3B), the corresponding genes do not form a coherent cluster in the non-demented state or LOAD, respectively. Thus, new modules are created in LOAD while in other cases a portion of the network is completely disrupted. The statistical significance of the MDC metrics was computed through the
