Knowledge-Guided Domain Adaptation Model for Transferring Drug Response Prediction from Cell Lines to Patients

Xuan Liu, Menglu Li

Abstract: Drug response prediction (DRP) is a longstanding challenge in modern oncology that underpins personalized treatment. Early DRP methods, trained on label-rich cell line samples, suffer from performance degradation when applied to label-scarce patient samples due to the distribution shift. Recently, a few transfer learning efforts have addressed this issue by aligning cell line (source domain) and patient (target domain) data via unsupervised domain adaptation (UDA). However, these efforts often treat each drug's response prediction as an isolated task, requiring model retraining when the drug changes; and focus only on aligning data distributions as a whole, neglecting the category (e.g., different cancers or tissues) confusion problem. To address these limitations, we propose a knowledge-guided domain adaptation model to transfer the DRP from cell lines to patients, named TransDRP. Specifically, TransDRP operates in two phases: pre-training and adaptation. In the first phase, we pre-train a multi-label graph neural network using molecular knowledge, to simultaneously predict responses for various drugs and capture their interdependencies. In the second phase, we implement a global-local domain adversarial strategy with clinical knowledge, to encourage representation alignment within same cancer categories and separation among different cancer categories across domains. Extensive experiments demonstrate that TransDRP outperforms state-of-the-art UDA methods in both transfer efficiency and precision for the patient DRP.