arXiv Machine Learning

TI$^2$PS: A Topology-Informed Inverse Design Framework for Stochastic Multicellular Pattern Formation

The paper introduces TI$^2$PS, a topology-informed inverse design framework that estimates agent-based model parameters to reproduce target multicellular patterns. It combines Betti vectors from topological data analysis with inverse surrogate modeling to address challenges in parameter estimation and topological evaluation under stochastic cell dynamics. Validation on zebrafish pigment pattern formation shows the framework outperforms conventional methods, achieving superior results with only 10% of the training data.

arXiv Machine Learning
Sep 25

SpaFactor: Lightweight Spatial Context-Aware Gene Program Modeling for Histology-to-Transcriptomics Inference

SpaFactor is a lightweight framework that predicts spatial gene expression from hematoxylin and eosin images by fusing central spot visuals with multiscale neighborhood context. It uses a residual MLP to map tissue microenvironment to low‑dimensional latent gene programs, which are decoded into coordinated multi‑gene predictions. Across five public cohorts, SpaFactor outperforms existing methods, especially for spatially variable genes, and better recovers biologically organized spatial patterns.

By Shiting Ruan, Xitong Ling, Qiming He, Ziyou Yan, Huaitian Yuan, Tian Guan, Ying Xiao, Xu Guan, Yonghong He
arXiv Machine Learning
Aug 18

A Unified Geometric Framework for Developmental Analysis of Spatial Transcriptomic Data

arXiv:2608. 15306v1 Announce Type: cross Abstract: High-throughput single-cell and spatial transcriptomic technologies provide high-resolution snapshots of heterogeneous cellular states, but their destructive nature prevents repeated measurements of the same cells over time.

By Mary Chriselda Antony Oliver, Kaitlyn Hohmeier, Tuyen Tran, Alejandra Castillo, Caroline Moosm\"uller, Shiying Li
arXiv Machine Learning
Oct 5

Generalizable single-cell perturbation response prediction using energy-guided flow matching

The paper introduces scEGFlow, an energy‑guided flow matching framework that predicts how single cells respond to perturbations by modeling continuous transitions from control to perturbed states. It uses conditional flow matching and condition‑specific energy gradients to dynamically adjust predictions without retraining, achieving superior performance on imaging and transcriptomic benchmarks, even for unseen perturbations or limited data. The method preserves cellular manifold geometry, heterogeneity, and accurately recapitulates gene‑expression regulatory patterns.

By Jianan Wei, Jiajun Hong, Guikun Chen, Ning Yang, Lifeng Fan, Wenguan Wang
arXiv Machine Learning
Sep 23

Simulation-free Structure Learning for Stochastic Population Dynamics

arXiv:2510.16656v2 Announce Type: replace Abstract: Modeling dynamical systems and unraveling their underlying structural dependencies is central to many domains in the natural sciences. Various phys...

By Noah El Rimawi-Fine, Adam Stecklov, Lucas Nelson, Mathieu Blanchette, Alexander Tong, Stephen Y. Zhang, Lazar Atanackovic
arXiv AI
Sep 28

LapDDPM: Spectral Perturbation Diffusion for Robust Single-Cell Manifold Generation

LapDDPM is a conditional Graph Diffusion Probabilistic Model that generates high‑fidelity, biologically plausible single‑cell RNA sequencing data. It incorporates graph‑based inductive biases and a spectral adversarial perturbation mechanism to enforce robustness against structural noise, effectively acting as a Distributionally Robust Optimization framework. The model extends to spatial transcriptomics and multi‑modal data, and experimental results on datasets such as PBMC3K, Dentate Gyrus, HLCA, Visium, and 10x Multiome show it outperforms state‑of‑the‑art baselines in distribution matching, manifold preservation, and downstream utility.

By Lorenzo Bini, Stephane Marchand-Maillet
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