arXiv:2608. 16419v1 Announce Type: cross Abstract: Large language models can describe mechanisms, yet scalable post-training still depends on costly, manually curated biological reasoning traces.
By Zhenchao Tang, Xiaogang Xu, Tianxu Lv, Jiahui Guan, Jiale Zhou, Haohuai He, Zhi Song, Hanbo Huang, Jiehui Huang, Jiafei Wu, Zhe Liu
CellRFT is a reinforcement fine‑tuning framework designed to improve single‑cell perturbation modeling by directly optimizing biological evaluation metrics. It employs policy‑gradient methods to learn from non‑differentiable biological rewards and aggregates multiple rewards hierarchically. Experiments show that CellRFT enhances perturbation prediction across various pretrained models and reveals interactions between different biological criteria, suggesting new ways to shape model behavior and evaluation design.
By Jie Yan, Li Liu, Hanze Guo, Jiaxin Hu, Houxin He, Xiaoning Qi, Haoran Wang, Cong Li, Zhong-Yuan Zhang, Yong Wang
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:2608. 01734v1 Announce Type: new Abstract: Predicting transcriptomic responses to small-molecule perturbations across cell lines is central to drug discovery, but exhaustive profiling of drug-cell combinations is infeasible.
By Betty Xiong, Jan-Christian Huetter, Gabriele Scalia, Tommaso Biancalani, Sepideh Maleki
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: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: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: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.
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:2606. 08816v1 Announce Type: cross Abstract: Predicting the effect of an unseen gene knockout perturbation on transcriptomic gene expression remains a highly challenging problem for virtual cell models.
By Jake Fawkes, Liam Hodgson, Jason Hartford
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