--- library_name: transformers license: mit base_model: - KuanP/PULSAR-pbmc --- # Model Card for PULSAR-pbmc **PULSAR** (Patient Understanding Leveraging Single-cell universAl Representation) is a multi-scale, multi-cellular foundation model for human peripheral blood mononuclear cells (PBMCs). It transforms a set of single-cell transcriptomes into an interpretable **donor-level embedding** that preserves single-cell resolution while capturing multicellular composition and coordination. This repo hosts the **aligned PBMC model** (`PULSAR-aligned`) used to produce donor embeddings aligned for disease classification. A base-model is also available (see **Model Sources**). ## Model Details ### Model Description PULSAR (Patient Understanding Leveraging Single-cell universAl Representation) is a hierarchical, multi-scale foundation model for PBMC scRNA-seq that converts unordered sets of single cells into a 512-d donor embedding while preserving single-cell resolution. It integrates molecular priors from ESM2 protein embeddings, cellular representations via Universal Cell Embeddings (UCE, 1,280-d), and a Multicellular Transformer encoder–decoder trained with a high-masking, Masked Cell Modeling objective. Pretraining proceeds in two stages: a pan-tissue CELLxGENE corpus (≈36.2M cells; 6,807 samples) followed by continual pretraining on blood (≈8.74M cells; 2,588 samples). The resulting donor embeddings support zero-shot and lightweight-head downstream tasks, including large-scale reference mapping for disease classification (state-of-the-art accuracy with strong external generalization), regression of plasma proteomics from transcriptomes, forecasting of future outcomes (e.g., RA conversion in ACPA+ individuals and influenza vaccine responsiveness), and individualized cytokine perturbation modeling across donor, cellular, and gene levels. A “virtual instrument” conditions on cytokine protein embeddings to transform baseline donor states and, with the decoder and an optional UCE→expression head, generates perturbed cell distributions and gene programs. Attention over cells provides mechanistic interpretability, highlighting disease- and severity-relevant subsets and enriching for antigen-specific clonotypes in viral infection. PULSAR thus operationalizes the AI Virtual Cell vision by linking molecular, cellular, and multicellular organization into a unified, transferable representation for precision immunology. - **Developed by:** Kuan Pang (Stanford University, kuanpang@stanford.edu) - **Model type:** Transformer - **License:** MIT ### Model Sources [optional] - **Repository:** https://github.com/snap-stanford/PULSAR - **Paper:** https://www.biorxiv.org/content/10.1101/2025.11.24.685470v1 - **Aligned version:** https://huggingface.co/KuanP/PULSAR-pbmc ## Uses ### Direct Use - Generate 512-d **donor embeddings** from PBMC scRNA-seq to: - Perform **reference mapping/retrieval** (kNN) for disease phenotypes ### Out-of-Scope Use The model might not work for tissue types other than PBMC, which also includes cell sorting samples. ## How to Get Started with the Model Use the code below to get started with the model. ## Training Details ### Training Data Stage-1 pretraining corpus: CZ CELLxGENE Census (LTS 2023-07-25), 36.2M cells, 6,807 samples across 53 tissues and 69 conditions. Stage-2 continual pretraining (blood focus): 8.736M cells, 2,588 blood/PBMC samples (balanced sexes; broad ages). More details can be found in the Paper and GitHub. ## Citation **BibTeX:** ``` @article{pang2025pulsar, title={PULSAR: a Foundation Model for Multi-scale and Multicellular Biology}, author={Pang, Kuan and Rosen, Yanay and Kedzierska, Kasia and He, Ziyuan and Rajagopal, Abhe and Gustafson, Claire E and Huynh, Grace and Leskovec, Jure}, journal={bioRxiv}, pages={2025--11}, year={2025}, publisher={Cold Spring Harbor Laboratory} } ```