PopPert is a framework that models population-level joint gene expression distributions to predict transcriptional responses to perturbations in single-cell RNA sequencing data. By using a low‑rank Gaussian Copula, it captures gene co‑expression patterns and eliminates the need for cell‑to‑cell correspondence, thereby reducing sensitivity to single‑cell noise. Across multiple benchmarks, PopPert outperforms existing methods in differential expression recovery, perturbation effect estimation, and distribution matching, demonstrating the effectiveness of population‑level joint distribution learning for unpaired single‑cell data.
By Handong Wang, Jiaxin Qi, Haochen Feng, Baisheng Lai
arXiv:2606. 12838v1 Announce Type: cross Abstract: Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks.
By Danning Jiang, Zheming An, Yalong Zhao, Lipeng Lai
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. 13713v1 Announce Type: cross Abstract: Predicting cellular transcriptional responses to genetic perturbations is a central problem in single-cell biology, especially in the zero-shot setting where the perturbed gene or gene combination is unseen during training.
By Wei Zhang, Xun Jiang, Yuesi Xi, Ming Tang
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: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:2511. 02986v2 Announce Type: replace-cross Abstract: Computational modeling of single-cell gene expression is crucial for understanding cellular processes, but generating realistic expression profiles remains a major challenge.
By Giovanni Palla, Sudarshan Babu, Payam Dibaeinia, James D. Pearce, Donghui Li, Aly A. Khan, Theofanis Karaletsos, Jakub M. Tomczak
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:2506. 22228v2 Announce Type: replace-cross Abstract: Single-cell sequencing is revolutionizing biology by enabling detailed investigations of cell-state transitions.
By Rong Ma, Xi Li, Jingyuan Hu, Bin Yu
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. 15288v1 Announce Type: new Abstract: Predicting single-cell transcriptomic responses to genetic perturbations is central to functional genomics and virtual-cell modeling.
By Ninghan Fan, Qi Liu, Xunuo Zhu, Yukai Sun, Luyuan Chen, Xuheng Zhou, Yuetian Du, Ming Kong, Xiaojun Zhu, Jie Liu, Zhan Zhou, Qiang Zhu
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