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: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:2606. 07760v1 Announce Type: new Abstract: Understanding cellular phenotypes and how they respond to perturbations is critical for disease biology and therapeutic design.
By Alma Andersson, Aya Abdelsalam Ismail, Edward De Brouwer, Doron Haviv, Tommaso Biancalani, Kyunghyun Cho, Gabriele Scalia, A\"icha BenTaieb, Hector Corrada Bravo
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:2603. 15263v2 Announce Type: replace-cross Abstract: Self-supervised learning (SSL) has revolutionized representation learning, with Joint-Embedding Architectures (JEAs) emerging as an effective approach for capturing semantic features.
By Konstantinos Almpanakis, Anna Kreshuk
arXiv:2607. 19426v1 Announce Type: cross Abstract: Single-cell datasets are increasingly costly to store, audit, and reuse for model training.
By Yaodi Luo, Peize He, Bowen Han, Lingbei Mengg
arXiv:2606. 27752v1 Announce Type: new Abstract: Single-cell perturbation models can reduce costly wet-lab screening by predicting how cells respond transcriptionally to interventions.
By Dongxia Wu, Mingyu Li, Yuhui Zhang, Anurendra Kumar, Emma Lundberg, Serena Yeung-Levy, Emily B. Fox
arXiv:2607. 22712v1 Announce Type: cross Abstract: Single-cell light microscopy images have become an important data source for characterizing cell phenotypes, but their complexity and heterogeneity pose challenges to high-throughput automated analysis.
By Yifan Shang (Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, China, College of Computer Science and Electronic Engineering, Hunan University, Changsha, China), Jiahui Tan (College of Computer Science and Electronic Engineering, Hunan University, Changsha, China), Xiangxiang Zeng (College of Computer Science and Electronic Engineering, Hunan University, Changsha, China), Renjie Zhou (Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, China)
The paper benchmarks six long‑tail loss functions—cross‑entropy, weighted CE, class‑balanced loss, focal loss, LDAM, and logit‑adjusted softmax—across three single‑cell foundation model architectures (scGPT, scBERT, Geneformer) and three datasets (Multiple Sclerosis, Zheng68K, human Pancreas). It shows that overall accuracy masks systematic failures on rare, disease‑relevant cell types, with a consistent gap between overall accuracy, Macro‑F1, and rare‑class recall under plain cross‑entropy. The study identifies two distinct regimes of rare‑class failure, predicts reweighting efficacy by absolute training‑set size, and finds class‑balanced loss and LDAM to be the most reliable across all settings.
By Zeyu Dong, Jiahui Zhong
arXiv:2602. 04901v2 Announce Type: replace-cross Abstract: Predicting transcriptional responses to genetic perturbations is a central problem in functional genomics.
By Jiafa Ruan, Ruijie Quan, Liyang Xu, Zongxin Yang, Yi Yang
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