Interpretable Recurrent Neural Networks for Modeling Temporal Dynamics of Acquired Drug Resistance in Targeted Therapy
| dc.contributor.author | Pushpalatha V. | |
| dc.contributor.author | Thanvi Kuttaiah | |
| dc.contributor.author | Kamaleshwar T. | |
| dc.contributor.author | Anat Jaslin Jini A. | |
| dc.contributor.author | Jakkapu Nagalakshmidevi | |
| dc.contributor.author | Susmitha V. | |
| dc.contributor.author | Sathyaraju S. | |
| dc.contributor.author | Jayasudha R. | |
| dc.contributor.author | Deepa A.R | |
| dc.contributor.author | Vengatesh T | |
| dc.date.accessioned | 2026-05-26T09:11:34Z | |
| dc.date.available | 2026-05-26T09:11:34Z | |
| dc.date.issued | 2026-05-26 | |
| dc.description.abstract | Acquired drug resistance remains a fundamental obstacle in targeted cancer therapy, often arising from complex temporal evolutionary dynamics within tumor cell populations. Traditional pharmacokinetic-pharmacodynamic (PKPD) models struggle to capture nonlinear, long-term sequential dependencies, while standard recurrent neural networks (RNNs) suffer from black-box opacity. In this paper, we propose IRNN-DR (Interpretable RNN for Drug Resistance), a novel architecture combining Long Short-Term Memory (LSTM) units with an attention-based temporal relevance mask and a learnable dynamical system backbone. Using longitudinal single- cell resistance data from EGFR-mutant non-small cell lung cancer (NSCLC) cell lines treated with osimertinib, we demonstrate that IRNN-DR achieves high predictive accuracy (AUC-ROC = 0.94) while providing explicit interpretations of resistance-driving time points and genetic pathways. Our contribution includes a temporal Shapley value module and a resistance trajectory clustering method. Results indicate that IRNN-DR can identify early "critical windows" of resistance emergence, with potential clinical utility for adaptive therapy scheduling | |
| dc.identifier.uri | http://192.168.75.5:4000/handle/123456789/21421 | |
| dc.title | Interpretable Recurrent Neural Networks for Modeling Temporal Dynamics of Acquired Drug Resistance in Targeted Therapy | |
| dc.type | Learning Object |