02024nas a2200193   4500008004100000022001400041245003600055210003600091260000800127300001100135490000700146520151300153653001801666653001801684653002401702100001801726700001901744856006701763       2021                        eng d  a1478-396700aBoolean model for melanogenesis0 aBoolean model for melanogenesis  cMAR  a0260040 v183 a<p>Melanogenesis is a highly regulated process through which the pigment melanin is produced in skin cells. Irregularities in the molecular events that govern the process of skin pigmentation can cause disorders like vitiligo. In order to understand the biology of disease progression, it is important to have an in depth understanding of intracellular events. Mathematical models provide an integrated view of intracellular signalling. There are very few models to date that incorporate intracellular processes relevant to melanogenesis and only one to our knowledge that simulates the dynamics of response to varying levels of input. Here, we report the formulation of the largest Boolean model (265 nodes) for melanogenesis to date. The model was built on the basis of a detailed interaction network graph published by Raghunath et al. Through additional manual curation of the reported interactions, we converted the graph into a set of Boolean rules, following the procedure of the first Boolean model (62 nodes) for melanogenesis published by Lee et al. Simulations show that the predicted response to varying UV levels for most of the nodes is similar to the predictions of the existing model. The greater complexity allows investigation of the sensitivity of melanin to additional nodes. We carried out perturbation analysis of the network through node deletion and constitutive activation to identify sensitivity of outcomes, and compared the nodes identified as sensitive to previous reports.</p>
10aBoolean model10amelanogenesis10aSignal transduction1 aDnyane, Pooja1 aGadgil, Chetan  uhttps://library.ncl.res.in/content/boolean-model-melanogenesis