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.
By Suyuan Zhao, Minghao Liu, Yizhen Luo, Zaiqing Nie
arXiv:2605.07938v2 Announce Type: replace
Abstract: Single-cell representation learning (SCRL) from gene expression data offers a way to uncover the complex regulatory logic underlying cellular funct...
By Sachini Weerasekara, Natasha Darras, Sagar Kamarthi, Colles Price, Jacqueline Isaacs
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:2608. 05928v1 Announce Type: new Abstract: Single-cell transcriptomes are sparse observations of coordinated biological programmes, yet most self-supervised models learn by reconstructing individual genes.
By Yuhao Wang, Zelin Zang, Yuxuan Liu, Zhen Lei, Stan Z. Li
arXiv:2606. 00685v1 Announce Type: new Abstract: Gene regulatory networks (GRNs) capture transcription factor-target interactions and are central to understanding cell-state regulation and disease.
By Tianyang Xu, Tianci Liu, Niraj Rayamajhi, Ryan Patrick, Kranthi Varala, Ying Li, Jing Gao
Single-cell transcriptomes are sparse observations of coordinated biological programmes, yet most self-supervised models learn by reconstructing individual genes. Here we present BioM-JEPA, a joint-embedding predictive architecture that instead predicts aggregate representations of graph-connected gene blocks defined by protein-association and corpus-derived coexpression evidence.
arXiv:2606. 14734v1 Announce Type: cross Abstract: Motivation: Gene regulatory network inference from single-cell RNA sequencing (scRNA-seq) data is important for uncovering cell-state-specific transcriptional programs.
By Ziyang Dong, Shanwen Tan, Hengchuang Yin, Wei Liu, Yifan Wang, Siyu Yi, Jiancheng Lv, Wei Ju
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:2512. 17678v2 Announce Type: replace-cross Abstract: Selecting compact and informative gene subsets from single-cell transcriptomic data is essential for biomarker discovery, improving interpretability, and cost-effective profiling.
By Daphn\'e Chopard, Jorge da Silva Gon\c{c}alves, Irene Cannistraci, Thomas M. Sutter, Julia E. Vogt
Accurate prediction of patient-specific therapeutic response from pre-treatment transcriptomes is hindered by the scarcity of matched clinical response labels and post-treatment molecular profiles. Preclinical transfer-learning models can simulate drug-induced expression changes but are often hard to interpret and unstable, whereas knowledge-graph methods provide mechanistic context yet remain static and fail to capture drug-induced transcriptomic perturbation dynamics.
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
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