PCA-based synthetic sensitivity coefficients for chemical reaction network in cancer

Abstract

Chemical reaction networks are powerful tools for modeling cell signaling and its disruptions in diseases like cancer. Realistic chemical reaction networks involve hundreds of proteins and reactions, resulting in a model depending on a consistently large number of kinetic parameters. Since finely calibrating all the parameters would require an unrealistic amount of data, proper sensitivity analysis is required to identify a subset of parameters for which fine tuning is needed and thus provide a fundamental tool for the qualitative analysis of the network. We present a multidisciplinary approach for computing a set of synthetic sensitivity indices. These indices rank the kinetic parameters, based on the impact that errors in their values would have on the protein concentration profile at equilibrium. Our tests on a chemical reaction network devised for colorectal cells demonstrate the effectiveness of the considered sensitivity indices in different scenarios including in-silico drug dosage and novel therapeutic target discovery. The Matlab code for computing the synthetic sensitivity indices and the data concerning the network for colorectal cells are available at https://github.com/theMIDAgroup/CRN_sensitivity.