Fig. 2

Flow diagram of the methodology. Starting from a specific experimental picture (discrete gene expression), we calculate the minimum number of lowly expressed genes required to be active for the cell to sustain cellular life (\(S_{a}^{wild}\)). Then, we systematically knock-out one by one all the expressed genes g present in the pathway P (Eg = 0) and recalculate the minimum number of lowly expressed genes required to be active for the cell to sustain cellular life (\(S_{a}^{g}\)). We define a gene as essential for a given active if \(S_{a}^{g} > S_{a}^{wild}\). We repeat this process for all the genes, actives, and pathways included in the database. The essentiality of a gene g is finally defined as the maximum of all its essentiality predictions across all actives A and pathways where the gene appears P_g