arXiv subjects

Monika Raj

Publications and source records attributed to Monika Raj.

3 recordsLinked to original sources

arXiv2026

Reinforcement Learning with LLM-Guided Action Spaces for Synthesizable Lead Optimization

Lead optimization in drug discovery requires improving therapeutic properties while ensuring that molecular modifications correspond to feasible synthetic routes. Existing approaches either prioritize property scores without enforcing synthesizability, or rely on expensive enumeration over large reaction networks, while direct application of Large Language Models (LLMs) to molecular generation frequently produces chemically invalid structures. We introduce MolReAct, a framework that formulates lead optimization as a Markov Decision Process over a synthesis-constrained action space defined by validated reaction templates. A tool-augmented LLM agent serves as a dynamic reaction environment, invoking specialized chemical analysis tools to identify reactive sites and functional groups and proposing a compact set of chemically grounded transformations from matched templates. A dedicated policy model trained via Group Relative Policy Optimization (GRPO) selects among these constrained actions to maximize long-term oracle reward across multi-step trajectories, with a SMILES-based caching mechanism reducing end-to-end optimization time by approximately 43%. Across 13 property optimization tasks from the Therapeutic Data Commons and one structure-based docking task, MolReAct achieves an average Top-10 score of 0.571, the highest among all baselines, ranking first or second on 13 of 14 tasks and attaining the best sample efficiency on 9 of 14 tasks. By grounding every optimization step in validated reaction templates, MolReAct produces molecules that are not only property-improved but each accompanied by an explicit template-grounded synthetic pathway.

cs.LG↗

arXiv2026

Imaging-anchored Multiomics in Cardiovascular Disease: Integrating Cardiac Imaging, Bulk, Single-cell, and Spatial Transcriptomics

Cardiovascular disease arises from interactions between inherited risk, molecular programmes, and tissue-scale remodelling that are observed clinically through imaging. Health systems now routinely generate large volumes of cardiac MRI, CT and echocardiography together with bulk, single-cell and spatial transcriptomics, yet these data are still analysed in separate pipelines. This review examines joint representations that link cardiac imaging phenotypes to transcriptomic and spatially resolved molecular states. An imaging-anchored perspective is adopted in which echocardiography, cardiac MRI and CT define a spatial phenotype of the heart, and bulk, single-cell and spatial transcriptomics provide cell-type- and location-specific molecular context. The biological and technical characteristics of these modalities are first summarised, and representation-learning strategies for each are outlined. Multimodal fusion approaches are reviewed, with emphasis on handling missing data, limited sample size, and batch effects. Finally, integrative pipelines for radiogenomics, spatial molecular alignment, and image-based prediction of gene expression are discussed, together with common failure modes, practical considerations, and open challenges. Spatial multiomics of human myocardium and atherosclerotic plaque, single-cell and spatial foundation models, and multimodal medical foundation models are collectively bringing imaging-anchored multiomics closer to large-scale cardiovascular translation.

q-bio.QM↗

arXiv2025

Peeling Context from Cause for Molecular Property Prediction

Deep models are used for molecular property prediction, yet they are often difficult to interpret and may rely on spurious context rather than causal structure, which reduces reliability under distribution shift and harms predictive performance. We introduce CLaP (Causal Layerwise Peeling), a framework that separates causal signal from context in a layerwise manner and integrates diverse graph representations of molecules. At each layer, a causal block performs a soft split into causal and non-causal branches, fuses causal evidence across modalities, and progressively removes batch-coupled context to focus on label-relevant structure, thereby limiting shortcut signals and stabilizing layerwise refinement. Across four molecular benchmarks, CLaP consistently improves MAE, MSE, and $R^2$ over competitive baselines. The model also produces atom-level causal saliency maps that highlight substructures responsible for predictions, providing actionable guidance for targeted molecular edits. Case studies confirm the accuracy of these maps and their alignment with chemical intuition. By peeling context from cause at every layer, the model yields predictors that are both accurate and interpretable for molecular design.

cs.LG↗