Optimal cancer prognosis under network uncertainty

Typically, a vast amount of experience and data is needed to successfully determine cancer prognosis in the face of (1) the inherent stochasticity of cell dynamics, (2) incomplete knowledge of healthy cell regulation, and (3) the inherent uncertain and evolving nature of cancer progression. There is hope that models of cell regulation could be used to predict disease progression and successful treatment strategies, but there has been little work focusing on the third source of uncertainty above. In this work, we investigate the impact of this kind of network uncertainty in predicting cancer prognosis. In particular, we focus on a scenario in which the precise aberrant regulatory relationships between genes in a patient are unknown, but the patient gene regulatory network is contained in an uncertainty class of possible mutations of some known healthy network. We optimistically assume that the probabilities of these abnormal networks are available, along with the best treatment for each network. Then, given a snapshot of the patient gene activity profile at a single moment in time, we study what can be said regarding the patient’s treatability and prognosis. Our methodology is based on recent developments on optimal control strategies for probabilistic Boolean networks and optimal Bayesian classification. We show that in some circumstances, prognosis prediction may be highly unreliable, even in this optimistic setting with perfect knowledge of healthy biological processes and ideal treatment decisions.