Symbolic Model Checking of Signaling Pathways in Pancreatic Cancer

摘要

Model Checking is a formal verification method widely used for the automated verification and analysis of hardware systems and digital circuits. In this work, we apply Model Checking to the study of a biological system - the HMGB1 Boolean network. Recent studies on pancreatic cancer cells have found that the overexpression of HMGB1, a DNA-binding protein, can decrease apoptosis (programmed cell death) and increase cancer cell survival. Also, knocking out HMGB1 or its receptors can increase apoptosis in cancer cells. In this paper, we first build a single-cell, Boolean network to model the crosstalk of three signaling pathways activated by HMGB1. Then, we apply Model Checking to formally query and verify some desired temporal logic properties of the HMGB1 model. The Boolean network modeling and Model Checking provide an alternative way and new insights into the study of the HMGB1 signaling pathway in pancreatic cancer.