PiDeeL: metabolic pathway-informed deep learning model for survival analysis and pathological classification of gliomas.

Motivation: Online assessment of tumor characteristics during surgery is important and has the potential to establish an intra-operative surgeon feedback mechanism. With the availability of such feedback, surgeons could decide to be more liberal or conservative regarding the resection of the tumor. While there are methods to perform metabolomics-based tumor pathology prediction, their model complexity predictive performance is limited by the small dataset sizes. Furthermore, the information conveyed by the feedback provided on the tumor tissue could be improved both in terms of content and accuracy.

Results: In this study, we propose a metabolic pathway-informed deep learning model (PiDeeL) to perform survival analysis and pathology assessment based on metabolite concentrations. We show that incorporating pathway information into the model architecture substantially reduces parameter complexity and achieves better survival analysis and pathological classification performance. With these design decisions, we show that PiDeeL improves tumor pathology prediction performance of the state-of-the-art in terms of the Area Under the ROC Curve by 3.38% and the Area Under the Precision-Recall Curve by 4.06%. Similarly, with respect to the time-dependent concordance index (c-index), PiDeeL achieves better survival analysis performance (improvement of 4.3%) when compared to the state-of-the-art. Moreover, we show that importance analyses performed on input metabolite features as well as pathway-specific neurons of PiDeeL provide insights into tumor metabolism. We foresee that the use of this model in the surgery room will help surgeons adjust the surgery plan on the fly and will result in better prognosis estimates tailored to surgical procedures.

Availability And Implementation: The code is released at https://github.com/ciceklab/PiDeeL. The data used in this study are released at https://zenodo.org/record/7228791.