arXiv:2608.23114v1 Announce Type: cross
Abstract: Predicting transcriptome-wide responses to unseen genetic perturbations remains a major computational challenge because accurate prediction requires...
By Jiawen Liu, Xuechenxiao Cao, Yutong Li, Bing Liu, Jiaming Liang, Tinghe Zhang, Xiaoqi Sheng, Hongmin Cai
SCALE is a conditional transport model that treats cells as unordered sets to predict treated cell populations without requiring cell-level matching. It uses a shared set-aware encoder and a conditional DiT backbone to learn latent transport, enabling endpoint supervision that is directly delta-aligned. Across diverse perturbation types—including genetic, chemical, developmental, and immune—SCALE accurately recovers gene‑expression changes, response directions, and population structure, outperforming competing methods on CRISPR data and successfully prioritizing cytokines that elicit distinct immune responses.
By Shuizhou Chen, Lang Yu, Xueqin Lin, Xinjie Mao, Songming Zhang, Xinyu Gu, Hao Wu, Sheng Xu, Kedu Jin, Lei Bai, Quan Qian, Qin Chen, Qiang Gao, Siqi Sun, Zhangyang Gao
arXiv:2608. 06824v1 Announce Type: cross Abstract: A central task in virtual cell modeling is predicting single-cell transcriptional responses to unseen genetic perturbations and drug combinations, and biological networks provide valuable priors on gene relationships.
By Quanquan Li, Yihe Chi, Liuyang Song, Hongbo Zhang, Jingyu Li, Xidong Xi, Conghua Wei, Yijie Sun, Yu Chen, Xin Liu, Qi Hu, Jing Ke, Guitao Cao
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:2607. 23447v1 Announce Type: new Abstract: Predicting cellular responses to unseen chemical perturbations is challenging due to unknown targets and mechanisms, high-dimensional expression responses, and limited experimental coverage of the large small-molecule design space.
By Yuche Gao, Jos\'e Miguel Hern\'andez-Lobato, Siyuan Guo
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: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
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:2606. 30695v1 Announce Type: cross Abstract: Single-cell drug perturbation models should predict not only transcriptional response magnitude, but also whether a treatment alters the proliferative state of a cell.
By Dingping Zhao, Jie Lin
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: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