Fig. 1.

Pipeline of the analysis. The analysis proceeds by following two branches. [Left, grey arrows] The human interactome network obtained from [21] and the lists of disease genes retrieved from Phenopedia [30] for the analyzed disorders (blue box, Input data) were given as input of the Random Walk with Restart (RWR) algorithm (red box, Method), which provided as output (purple box, Outcome) the human disease network, where nodes are diseases and a link occurs between two diseases if, starting from one disease module, the other one is more likely to be reached by a random walker on the interactome. [Right, turquoise arrows] The human interactome network, the lists of disease genes, and the drug-target interactions downloaded from DrugBank [31] (blue box, Input data) were given as input to SAveRUNNER algorithm (red box, Method), which provided as output (purple box, Outcome) the drug-disease network, where nodes are FDA-approved drugs and diseases, and a link occurs if a drug is predicted to be repositioned for that disease. Among the drugs predicted by SAveRUNNER as potentially repurposable for ALS disease, we focused on those drugs that are histaminergic modulators and whose original medical indications referred to diseases connected to ALS in the human disease network