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. 02961v1 Announce Type: cross Abstract: We study a self-supervised generation task for single-cell gene expression vectors: given a set of vectors from a cell type, we aim to generate additional gene expression vectors of that cell type.
By Aleksandr Sharipov, Yusif Mukhtarov, Igor Molybog
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
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: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
arXiv:2607. 14163v1 Announce Type: cross Abstract: Most single-cell foundation models are adapted from language models, representing each cell as a sequence of gene tokens.
By Ridvan Yesiloglu, Sakib Mostafa, James Zou, Ash Alizadeh, Jiajun Wu, Lei Xing, Ehsan Adeli, Md Tauhidul Islam