Modeling drug response using network-based personalized treatment prediction (NetPTP) with applications to inflammatory bowel disease

Abstract

For many prevalent complex diseases, treatment regimens are frequently ineffective. For example, despite multiple available immunomodulators and immunosuppressants, inflammatory bowel disease (IBD) remains difficult to treat. Heterogeneity in the disease across patients makes it challenging to select the optimal treatment regimens, and some patients do not respond to any of the existing treatment choices. Drug repurposing strategies for IBD have had limited clinical success and have not typically offered individualized patient-level treatment recommendations. In this work, we present NetPTP, a Network-based Personalized Treatment Prediction framework which models measured drug effects from gene expression data and applies them to patient samples to generate personalized ranked treatment lists. To accomplish this, we combine publicly available network, drug target, and drug effect data to generate treatment rankings using patient data. These ranked lists can then be used to prioritize existing treatments and discover new therapies for individual patients. We demonstrate how NetPTP captures and models drug effects, and we apply our framework to individual IBD samples to provide novel insights into IBD treatment.

Author summary

Offering personalized treatment results is an important tenant of precision medicine, particularly in complex diseases which have high variability in disease manifestation and treatment response. We have developed a novel framework, NetPTP (Network-based Personalized Treatment Prediction), for making personalized drug ranking lists for patient samples. Our method uses networks to model drug effects from gene expression data and applies these captured effects to individual samples to produce tailored drug treatment rankings. We applied NetPTP to inflammatory bowel disease, yielding insights into the treatment of this particular disease. Our method is modular and generalizable, and thus can be applied to other diseases that could benefit from a personalized treatment approach.