One important addition to the new version of WebGestalt includes functional categories defined by network modules, comprising protein–protein interaction network modules and regulatory modules. The former is a recent and unique addition to WebGestalt through computational network analysis. Although a few enrichment analysis tools support protein–protein interaction network-based enrichment analysis, they typically rely on gene sets derived from network decomposition at a single level without considering the hierarchical structure of the network. However, it is well-known that hierarchical organization is a critical intrinsic property of complex systems including biological networks (17). Recent works from the Ideker group (10) suggest that gene networks embed hierarchical structure that is consistent with GO and can extend beyond GO. Along the same line, WebGestalt has added functional categories defined by hierarchical protein interaction network modules. Specifically, for the human network, we combined from seven curated databases (Table 2) all protein–protein interaction data with at least one publication support to build an integrated protein–protein interaction network. For the mouse network, because the seven databases only contained a limited number of interactions, we first used an
