Integrating Drug Target Information in Deep Learning Models to Predict the Risk of Adverse Events in Patients with Comorbid Post-Traumatic Stress Disorder and Alcohol Use Disorder.

Background/

Objectives

Comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) patients are at a significantly higher risk of adverse outcomes, including opioid use disorder, depression, suicidal behaviors, and death, yet limited treatment options exist for this population. This study aimed to build on previous research by incorporating drug target information into a novel deep learning model, T-DeepBiomarker, to predict adverse outcomes and identify potential therapeutic medications.

Methods

We utilized electronic medical record (EMR) data from the University of Pittsburgh Medical Center (UPMC), analyzing 5565 PTSD + AUD patients. T-DeepBiomarker was developed by integrating multimodal data, including lab results, drug target information, comorbidities, neighborhood-level social determinants of health (SDoH), and individual-level SDoH (e.g., psychotherapy and veteran status). The model was trained to predict adverse events, including opioid use disorder, suicidal behaviors, depression, and death, within three months following any clinical encounter. Candidate medications targeting significant proteins were identified through literature reviews.

Results

T-DeepBiomarker achieved high predictive performance with an AUROC of 0.94 for adverse outcomes in PTSD + AUD patients. Several medications, including OnabotulinumtoxinA, Dronabinol, Acamprosate, Celecoxib, Exenatide, Melatonin, and Semaglutide, were identified as potentially reducing the risk of adverse events by targeting significant proteins.

Conclusions

T-DeepBiomarker demonstrates high accuracy in predicting adverse outcomes in PTSD + AUD patients and highlights candidate drugs with potential therapeutic effects. These findings advance pharmacotherapy for this high-risk population and identify medications that warrant further investigation.