Fig. 4. Network modules of rare genetic gastroenterological diseases across different levels of biological organization.

Genes implicated in rare gastroenterological disease form significant modules on five network layers (compare with Fig. 3), which capture relevant relationships on different scales. Diseases in the disease group exhibit unique connectivity patterns in the network layers where their disease characteristics can be derived. For example, a strong phenotypic cluster of Bardet-Biedl syndrome genes can be derived from the protein complex (BBSome) whose defects lead to cilia dysfunction, while pancreatic carcinoma cluster is most observable on the pathway level where its causal genes interact physically and are also member of crucial signaling pathways. The treemap represents disease entries in Orphanet (leaf terms with at least two gene associations) that belong to the rare genetic gastroenterological disease group (69 diseases with only one gene association are not shown separately).