# scMamba: A Pre-Trained Model for Single-Nucleus RNA Sequencing Analysis in Neurodegenerative Disorders

arXiv: https://arxiv.org/abs/2502.19429 · HTML: https://mlsanity.com/paper/2502.19429/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Mamba for medical image analysis, one of 10 directions in State-space sequence models (S4, Mamba).
- Builds on 14 of its 63 references that are in the map.
- First posted on arXiv 12 Feb 2025.

## Placed in

- State-space sequence models (S4, Mamba) / [Mamba for medical image analysis](https://mlsanity.com/ssm/mamba-for-medical-image-analysis/)

## Builds on (most cited first, 14 of 14)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Mamba: Linear-Time Sequence Modeling with Selective State Spaces](https://mlsanity.com/paper/2312.00752/) (2023)
- [Zero-Shot Text-to-Image Generation](https://mlsanity.com/paper/2102.12092/) (2021)
- [On the Opportunities and Risks of Foundation Models](https://mlsanity.com/paper/2108.07258/) (2021)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [Rethinking Attention with Performers](https://mlsanity.com/paper/2009.14794/) (2020)
- [Vision Mamba: Efficient Visual Representation Learning with Bidirectional State Space Model](https://mlsanity.com/paper/2401.09417/) (2024)
- [Hyena Hierarchy: Towards Larger Convolutional Language Models](https://mlsanity.com/paper/2302.10866/) (2023)
- [MambaIR: A Simple Baseline for Image Restoration with State-Space Model](https://mlsanity.com/paper/2402.15648/) (2024)
- [Caduceus: Bi-Directional Equivariant Long-Range DNA Sequence Modeling](https://mlsanity.com/paper/2403.03234/) (2024)
- [VL-Mamba: Exploring State Space Models for Multimodal Learning](https://mlsanity.com/paper/2403.13600/) (2024)
- [MambaMIR: An Arbitrary-Masked Mamba for Joint Medical Image Reconstruction and Uncertainty Estimation](https://mlsanity.com/paper/2402.18451/) (2024)
- [scHyena: Foundation Model for Full-Length Single-Cell RNA-Seq Analysis in Brain](https://mlsanity.com/paper/2310.02713/) (2023)

## Abstract (arXiv)

Single-nucleus RNA sequencing (snRNA-seq) has significantly advanced our understanding of the disease etiology of neurodegenerative disorders. However, the low quality of specimens derived from postmortem brain tissues, combined with the high variability caused by disease heterogeneity, makes it challenging to integrate snRNA-seq data from multiple sources for precise analyses. To address these challenges, we present scMamba, a pre-trained model designed to improve the quality and utility of snRNA-seq analysis, with a particular focus on neurodegenerative diseases. Inspired by the recent Mamba model, scMamba introduces a novel architecture that incorporates a linear adapter layer, gene embeddings, and bidirectional Mamba blocks, enabling efficient processing of snRNA-seq data while preserving information from the raw input. Notably, scMamba learns generalizable features of cells and genes through pre-training on snRNA-seq data, without relying on dimension reduction or selection of highly variable genes. We demonstrate that scMamba outperforms benchmark methods in various downstream tasks, including cell type annotation, doublet detection, imputation, and the identification of differentially expressed genes.