Efficient Fine-Tuning of Single-Cell Foundation Models Enables Zero-Shot Molecular Perturbation Prediction

Predicting transcriptional responses to novel drugs provides a unique opportunity to accelerate biomedical research and advance drug discovery efforts. However, the inherent complexity and high dimensionality of cellular responses, combined with the extremely limited available experimental data, makes the task challenging. In this study, we leverage single-cell foundation models (FMs) pre-trained on tens of millions of single cells, encompassing multiple cell types, states, and disease annotations, to address molecular perturbation prediction. We introduce a drug-conditional adapter that allows efficient fine-tuning by training less than 1% of the original foundation model, thus enabling molecular conditioning while preserving the rich biological representation learned during pre-training. The proposed strategy allows not only the prediction of cellular responses to novel drugs, but also the zero-shot generalization to unseen cell lines. We establish a robust evaluation framework to assess model performance across different generalization tasks, demonstrating state-of-the-art results across all settings, with significant improvements in the few-shot and zero-shot generalization to new cell lines compared to existing baselines.

NetVec: A Scalable Hypergraph Embedding System

Many problems such as vertex classification andlink prediction in network data can be solvedusing graph embeddings, and a number of algo-rithms are known for constructing such embed-dings. However, it is difficult to use graphs tocapture non-binary relations such as communitiesof vertices. These kinds of complex relations areexpressed more naturally as hypergraphs. Whilehypergraphs are a generalization of graphs, state-of-the-art graph embedding techniques are notadequate for solving prediction and classificationtasks on large hypergraphs accurately in reason-able time. In this paper, we introduce NetVec,a novel multi-level framework for scalable un-supervised hypergraph embedding, that can becoupled with any graph embedding algorithm toproduce embeddings of hypergraphs with millionsof nodes and hyperedges in a few minutes.