arXiv AI

CellMSA: Context Modeling for Single-Cell Representation Learning

CellMSA introduces a novel single‑cell representation learning framework that leverages a multiple‑sequence‑alignment‑inspired context model. For each target cell, it retrieves relevant cells across batches and related cell types, summarizing cross‑cell patterns into a context‑dependent gene‑pair representation that is fed into a pair‑aware encoder. Pretraining on a massive human single‑cell corpus (≈109 million cells) and subsequent benchmarks demonstrate consistent performance gains over existing methods.

arXiv AI
Sep 3

Subcellularly Resolved Single-Cell Embedding Learning with Transcriptomic data, Protein Structure and Localization Information

The paper introduces a multimodal framework that learns subcellularly resolved cell embeddings by integrating RNA expression profiles, protein sequence representations, and protein structural information using a cross‑attention architecture. This approach models interactions within distinct subcellular compartments, producing fine‑grained embeddings that capture both molecular expression patterns and functional protein properties. It is presented as the first method to jointly incorporate transcriptomic data, sequence, and structural knowledge for subcellularly resolved cell representation.

By Zhen Zhou, Jiachen Li, Yuan Liu, Xiaoyong Pan, Hong-Bin Shen
arXiv AI
2d ago

scTrilemma: Balancing Identity, Invariance, and Fidelity in Single-Cell Representation Learning

The paper introduces scTrilemma, a latent-bottleneck variational autoencoder designed to address the representation trilemma in single‑cell RNA‑seq data: preserving biological identity and state, remaining robust to nuisance context, and retaining gene‑level variation for expression analysis. scTrilemma routes expression‑derived variation to the embedding, decoder, or prior, gating gene tokens by expression and conditioning the prior on unlabeled pseudo‑bulk context, all under a single reconstruction objective without target annotations. In zero‑shot evaluations on successive CZ CELLxGENE Census releases, scTrilemma simultaneously satisfies all three demands, maintaining biological state, differential‑expression, and pathway structure across multiple disease settings, and latent interventions show context can be removed with minimal impact on other demands.

By Yunhak Oh, Yoonho Lee, Junseok Lee, Namkyeong Lee, Sang-Yeon Hwang, Yinhua Piao, Hyomin Kim, Seonghwan Kim, Jaechang Lim, Woo Youn Kim, Sungsoo Ahn, Chanyoung Park
arXiv AI
Sep 15

Towards a knowledge-enhanced single-cell foundation model

The paper introduces scKITE, a single-cell foundation model that incorporates biological knowledge—cell-level text annotations and gene-level regulatory information—into a shared Transformer encoder via lightweight auxiliary decoders used only during pretraining. This approach provides a new scaling dimension beyond merely increasing data size, enabling the model to achieve superior performance on diverse downstream tasks with only 179,067 pretraining samples, less than 0.5% of the data used by previous strong scFMs. The study demonstrates that knowledge-enhanced pretraining can yield significant gains while reducing computational cost.

By Hanqing Zhang, Jie Bao, Mei Ma, Shuai Liu, Jiaying Ma, Jiaguan Liu, Jiaxiao Li, Zhenbo Li, Wenwen Gong, Zhijun Ca
Hugging Face Trending Papers
Sep 2

Subcellularly Resolved Single-Cell Embedding Learning with Transcriptomic data, Protein Structure and Localization Information

The paper introduces a multimodal framework that learns subcellularly resolved cell embeddings by integrating RNA expression profiles, protein sequence representations, and protein structural information. It uses a cross‑attention architecture to model interactions across distinct subcellular compartments, producing embeddings that capture both molecular expression patterns and functional protein properties. This approach is presented as the first to jointly incorporate transcriptomic data, protein sequences, and structural knowledge within a unified cross‑modal learning paradigm.

arXiv Machine Learning
Jun 9

Integrating gene regulatory priors into Transformer attention with scTransformer for interpretable scRNA-seq analysis

arXiv:2606. 09558v1 Announce Type: cross Abstract: Motivation: Transformer-based models are increasingly applied to large-scale single-cell transcriptomics, showing strong performance through self-supervised learning on millions of cells.

By Mikele Milia, Louis Fabrice Tshimanga, Henning Mueller, Manfredo Atzori, Barbara Di Camillo
arXiv Machine Learning
Jun 5

HEIST: A Graph Foundation Model for Spatial Transcriptomics and Proteomics Data

arXiv:2506. 11152v4 Announce Type: replace-cross Abstract: Single-cell transcriptomics and proteomics have become a great source for data-driven insights into biology, enabling the use of advanced deep learning methods to understand cellular heterogeneity and gene expression at the single-cell level.

By Hiren Madhu, Jo\~ao Felipe Rocha, Tinglin Huang, Siddharth Viswanath, Smita Krishnaswamy, Rex Ying