arXiv AI

$D^{2}R^{2}$: Discrete Diffusion with Regulation Reinforcement for Single-Cell Perturbation Prediction

arXiv:2608. 15288v1 Announce Type: new Abstract: Predicting single-cell transcriptomic responses to genetic perturbations is central to functional genomics and virtual-cell modeling.

arXiv AI
Aug 10

Control-Anchored Residual Flow Matching Conditioned on Gene Geometry for Virtual Cell Perturbation Modeling

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
arXiv Machine Learning
Sep 18

CellRFT: Reinforcement Fine-Tuning for Single-Cell Perturbation Modeling

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 AI
Jun 12

OCOO-T : A Simple and Scalable Virtual Cell Model for Transcriptional Perturbation Response Prediction

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
arXiv Machine Learning
Sep 18

VGAS: Variance-Reduced Guidance and Adaptive Selection for Training-Free Reward Alignment in Discrete Diffusion

VGAS: Variance-Reduced Guidance and Adaptive Selection for Training-Free Reward Alignment in Discrete Diffusion proposes a new inference-time framework that improves steering of frozen masked discrete diffusion models. By reducing the variance of guidance estimates, applying reward tilting to clean-token logits, and adapting the selection temperature at each step, VGAS addresses three default choices in existing pipelines. Experiments on regulatory DNA, protein, and small-molecule benchmarks show that VGAS achieves the best training-free reward performance and matches or surpasses reward-fine-tuned generators.

By Kwanyoung Kim
arXiv AI
Sep 2

PopPert: Population-level Joint-Distribution Modeling for Single-Cell Perturbation Prediction

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