PHENSIM: Phenotype Simulator

Motivation: Despite the unprecedented increase of our understanding of cell biology, connecting experimental data to the physiopathological status of cells and tissues under precise circumstances is still a challenge. This often results in difficulties during the design of validation experiments, which are usually labor-intensive, expensive to perform and hard to interpret. Results: Here we propose PHENSIM, a systems biology approach, which can simulate the effects of activation/inhibition of one or multiple biomolecules on cell phenotypes by exploiting signaling pathways. Possible applications of our tool include prediction of the outcome of drug administration, knockdown experiments, gene transduction and exposure to exosomal cargo. Importantly, this method allows the user to make inferences on well-defined cell lines and includes pathway maps from three different model organisms. The basic assumption is that phenotypes can be described through changes in pathway activity. Results from our study show discrete prediction accuracy, highlighting the capabilities of this methodology. Availability and Implementation: PHENSIM has been developed in Java and it is available, along with all data and source codes, at https://github.com/alaimos/phensim. A web-based user interface, developed in PHP is accessible at https://phensim.atlas.dmi.unict.it/.