Towards AI-Based Precision Oncology: A Machine Learning Framework for Personalized Counterfactual Treatment Suggestions based on Multi-Omics Data

AI-driven precision oncology has the transformative potential to reshape cancer treatment by leveraging the power of AI models to analyze the interaction between complex patient characteristics and their corresponding treatment outcomes. New technological platforms have facilitated the timely acquisition of multimodal data on tumor biology at an unprecedented resolution, such as single-cell multi-omics data, making this quality and quantity of data available for data-driven improved clinical decision-making. In this work, we propose a modular machine learning framework designed for personalized counterfactual cancer treatment suggestions based on an ensemble of machine learning experts trained on diverse multi-omics technologies. These specialized counterfactual experts per technology are consistently aggregated into a more powerful expert with superior performance and can provide both confidence and an explanation of its decision. The framework is tailored to address critical challenges inherent in data-driven cancer research, including the high-dimensional nature of the data, and the presence of treatment assignment bias in the retrospective observational data. The framework is showcased through comprehensive demonstrations using data from in-vitro and in-vivo treatment responses from a cohort of patients with ovarian cancer. Our method aims to empower clinicians with a reality-centric decision-support tool including probabilistic treatment suggestions with calibrated confidence and personalized explanations for tailoring treatment strategies to multi-omics characteristics of individual cancer patients.

Neural Unbalanced Optimal Transport via Cycle-Consistent Semi-Couplings

Comparing unpaired samples of a distribution or population taken at different points in time is a fundamental task in many application domains where measuring populations is destructive and cannot be done repeatedly on the same sample, such as in single-cell biology. Optimal transport (OT) can solve this challenge by learning an optimal coupling of samples across distributions from unpaired data. However, the usual formulation of OT assumes conservation of mass, which is violated in unbalanced scenarios in which the population size changes (e.g., cell proliferation or death) between measurements. In this work, we introduce NubOT, a neural unbalanced OT formulation that relies on the formalism of semi-couplings to account for creation and destruction of mass. To estimate such semi-couplings and generalize out-of-sample, we derive an efficient parameterization based on neural optimal transport maps and propose a novel algorithmic scheme through a cycle-consistent training procedure. We apply our method to the challenging task of forecasting heterogeneous responses of multiple cancer cell lines to various drugs, where we observe that by accurately modeling cell proliferation and death, our method yields notable improvements over previous neural optimal transport methods.