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: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
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
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: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
arXiv:2608. 00985v1 Announce Type: new Abstract: The rapid growth of single-cell transcriptomic data has enabled the development of foundation models pretrained primarily by reconstructing masked expression values.
By Jiaqi Xiong, Yuntao hu, Yu Zheng, Yifei Shi, Xinyue Guo, Jiaxin Qi
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:2606. 07676v1 Announce Type: cross Abstract: Spatial transcriptomics (ST) is a powerful tool for exploring biological properties dependent on structure, proximity, and interaction in tissue.
By Joseph Boyd, Matthew Lyon, Martino Mansoldo, Christian Hurry, Finnian Firth
arXiv:2607. 29043v1 Announce Type: cross Abstract: Single-cell RNA sequencing (scRNA-seq) has become an essential tool in modern cellular biology, and generating accurate synthetic scRNA-seq data is becoming increasingly important.
By Yu Song, Hao Sun, Ikuko Nishikawa, Yen-Wei Chen
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
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.
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