# From Cellular Responses to Pharmacological Domains: Multimodal Zero-Shot Drug Representation Learning

arXiv: https://arxiv.org/abs/2607.25322 · HTML: https://mlsanity.com/paper/2607.25322/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 28 references that are in the map.
- First posted on arXiv 28 Jul 2026.

## Builds on (most cited first, 11 of 11)

- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [Graph Contrastive Learning with Augmentations](https://mlsanity.com/paper/2010.13902/) (2020)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [Analyzing Learned Molecular Representations for Property Prediction](https://mlsanity.com/paper/1904.01561/) (2019)
- [3D Infomax improves GNNs for Molecular Property Prediction](https://mlsanity.com/paper/2110.04126/) (2021)
- [Self-supervised Graph-level Representation Learning with Local and Global Structure](https://mlsanity.com/paper/2106.04113/) (2021)
- [Can contrastive learning avoid shortcut solutions?](https://mlsanity.com/paper/2106.11230/) (2021)
- [On Uni-Modal Feature Learning in Supervised Multi-Modal Learning](https://mlsanity.com/paper/2305.01233/) (2023)
- [Learning Molecular Representation in a Cell](https://mlsanity.com/paper/2406.12056/) (2024)

## Abstract (arXiv)

Multimodal drug discovery enables drug representation learning beyond chemical structure by incorporating cellular responses such as gene expression and cell morphology. However, direct fusion and instance-level contrastive alignment may mix mechanism-related signals with modality-specific noise and incorrectly separate structurally dissimilar but biologically related compounds. This limitation can obscure transferable mechanism patterns required for predicting the properties of unseen compounds. We introduce PMRD, a pharmacological response domain-guided framework for multimodal zero-shot drug property prediction. PMRD separates mechanism-consistent factors from modality-specific information and constructs a consensus response domain across three modalities. Mechanism candidate augmentation identifies locally stable factors, while retrieval-geometry attribution dynamically reweights the alignment and augmentation objectives according to whether their updates preserve inter-drug discriminability.This feedback suppresses training signals that conflict with mechanism-discriminative retrieval. PMRD further combines complementary representations through reliability-aware multiview retrieval. Experiments on public datasets show improved zero-shot property prediction and more biologically coherent drug neighborhoods. Hard-negative analysis further indicates fewer conflicts between structurally dissimilar but response-related compounds. These results support PMRD as an effective framework for mechanism-aware multimodal drug representation learning.footnoteThe code will be released upon publication.