Our algorithm then checks the clique size in descending order, until size two. For a clique size k, if there is no clique with the same size, it can still be merged into a community if at least 70% of the nodes are members of the community. The overlapping communities can thus be generated through this backward clique percolation algorithm. For the percolation steps in our algorithm, the runtime is linear in terms of the number of cliques, as shown in. For the community merging steps, the worse-case runtime is quadratic in terms of the number of communities, which is usually a much smaller number than the number of nodes or cliques. Note that SECOM predicts the conserved regions of the domains instead of estimating the exact boundaries of the domains. To predict the boundaries, one can apply the widely used method in local Temozolomide alignment algorithms, which extends the aligned conserved regions in both directions until the alignment score is lower than a certain threshold. Biological features can also be extracted to enhance the prediction accuracy for boundaries. Since these are not the main focus of the paper, we leave it as a user option. Regulated insulin secretion from pancreatic beta-cells is required for normal glucose homeostasis. However, the molecular pathways underlying glucose-stimulated insulin secretion are complex and remain incompletely understood. In order to secrete insulin in response to glucose, beta-cells must sense a rise in extracellular glucose which in turn leads to a stimulus-secretion coupling cascade that triggers insulin granule exocytosis. Glucose is ‘sensed’ via an increase in the ATP to ADP ratio. Glucose enters the beta-cell via facilitative glucose transporters, and is then metabolised via the glycolytic pathway, Krebs cycle and the electron transport chain to generate 34–36 molecules of ATP per molecule of metabolised glucose. Increased ATP:ADP closes K channels, leading to membrane depolarisation; this in turn leads to the opening of voltage-dependent calcium channels in the cell membranes, facilitating calcium influx into the beta-cell. Insulin granule trafficking and insulin exocytosis in beta-cells are ATP and calcium dependent processes. Gem belongs to the RGK family of Ras-related GTPases, which includes Rad, Rem, and Rem2. While relatively little is known about the physiological roles of RGK family members, all RGK proteins are known to be capable of modulating VDCC function, with Gem and Rad also able to regulate cytoskeletal dynamics. The conserved ability of all RGK proteins to potently inhibit VDCCs, suggests that tissue-specific patterns of expression contribute to the functional differences between family members. Previous studies reported expression of Gem and Rem2 in rodent pancreatic beta-cells. Analysis of human islets indicate that multiple RGK family members are expressed in betacells, but further expression studies are required to focus specifically on beta-cells within the islet. The genes encoding detoxification enzymes belong to supergene families which have evolved predominantly by gene duplication and functional diversification.