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The advent of single-cell technology has significantly improved our understanding of cellular states and subpopulations in various tissues under normal and diseased conditions by employing data-driven approaches such as clustering and…

Single-cell perturbation prediction aims to infer how cells respond to unseen interventions and to achieve out-of-distribution (OOD) generalization, providing a computational route to understanding how perturbations reshape cellular…

Machine Learning · Computer Science 2026-05-26 Wenkang Jiang , Yuhang Liu , Erdun Gao , Ehsan Abbasnejad , Lina Yao , Javen Qinfeng Shi

Predicting how genetic perturbations change cellular state is a core problem for building controllable models of gene regulation. Perturbations targeting the same gene can produce different transcriptional responses depending on their…

Genomics · Quantitative Biology 2026-02-12 Boyang Fu , George Dasoulas , Sameer Gabbita , Xiang Lin , Shanghua Gao , Xiaorui Su , Soumya Ghosh , Marinka Zitnik

Recent developments in synthetic biology, next-generation sequencing, and machine learning provide an unprecedented opportunity to rationally design new disease treatments based on measured responses to gene perturbations and drugs to…

Molecular Networks · Quantitative Biology 2024-03-12 Thomas P. Wytock , Adilson E. Motter

Single-cell trajectory analysis aims to reconstruct the biological developmental processes of cells as they evolve over time, leveraging temporal correlations in gene expression. During cellular development, gene expression patterns…

Applications · Statistics 2026-03-30 Junhao Zhu , Kevin Zhang , Zhaolei Zhang , Dehan Kong

Predicting single-cell perturbation outcomes directly advances gene function analysis and facilitates drug candidate selection, making it a key driver of both basic and translational biomedical research. However, a major bottleneck in this…

Machine Learning · Computer Science 2025-11-18 Changxi Chi , Yufei Huang , Jun Xia , Jiangbin Zheng , Yunfan Liu , Zelin Zang , Stan Z. Li

Predicting the effects of perturbations in-silico on cell state can identify drivers of cell behavior at scale and accelerate drug discovery. However, modeling challenges remain due to the inherent heterogeneity of single cell gene…

A key problem in computational biology is discovering the gene expression changes that regulate cell fate transitions, in which one cell type turns into another. However, each individual cell cannot be tracked longitudinally, and cells at…

Machine Learning · Computer Science 2022-07-12 Yichen Gu , David Blaauw , Joshua Welch

Spatial transcriptomics (ST) enables spatially resolved gene profiling but remains expensive and low-throughput, limiting large-cohort studies and routine clinical use. Predicting spatial gene expression from routine hematoxylin and eosin…

Computer Vision and Pattern Recognition · Computer Science 2026-04-24 Changfan Wang , Xinran Wang , Donghai Liu , Fei Su , Lulu Sun , Zhicheng Zhao , Zhu Meng

Virtual cell models aim to enable in silico experimentation by predicting how cells respond to genetic, chemical, or cytokine perturbations from single-cell measurements. In practice, however, large-scale perturbation prediction remains…

Machine Learning · Computer Science 2026-03-20 Shuizhou Chen , Lang Yu , Kedu Jin , Songming Zhang , Hao Wu , Wenxuan Huang , Sheng Xu , Quan Qian , Qin Chen , Lei Bai , Siqi Sun , Zhangyang Gao

Predicting drug-induced cellular state changes at single-cell resolution remains a central challenge in virtual cell modeling, particularly under out-of-distribution (OOD) conditions. Current approaches predominantly rely on RNA-based…

Genomics · Quantitative Biology 2026-05-18 Peiting Shi , Ningfeng Que , Xianzhe Huang , Xiaofei Wang , Jianzhong Jeff Xi

Modern high-throughput biological datasets with thousands of perturbations provide the opportunity for large-scale discovery of causal graphs that represent the regulatory interactions between genes. Differentiable causal graphical models…

Machine Learning · Computer Science 2025-11-14 Zaikang Lin , Sei Chang , Aaron Zweig , Minseo Kang , Elham Azizi , David A. Knowles

Modeling the evolution of system with time-series data is a challenging and critical task in a wide range of fields, especially when the time-series data is regularly sampled and partially observable. Some methods have been proposed to…

Machine Learning · Computer Science 2024-12-03 Mengbang Zou , Weisi Guo

We develop a novel data-driven framework as an alternative to dynamic flux balance analysis, bypassing the demand for deep domain knowledge and manual efforts to formulate the optimization problem. The proposed framework is end-to-end,…

Machine Learning · Computer Science 2024-10-21 Santanu Rathod , Pietro Lio , Xiao Zhang

A central goal in systems biology and drug discovery is to predict the transcriptional response of cells to perturbations. This task is challenging due to the noisy and sparse nature of single-cell measurements, as well as the fact that…

Quantitative Methods · Quantitative Biology 2026-02-10 Chenglei Yu , Chuanrui Wang , Bangyan Liao , Tailin Wu

Generative modeling can be formulated as learning a mapping f such that its pushforward distribution matches the data distribution. The pushforward behavior can be carried out iteratively at inference time, for example in diffusion and…

Machine Learning · Computer Science 2026-02-09 Mingyang Deng , He Li , Tianhong Li , Yilun Du , Kaiming He

Simulating the time evolution of Partial Differential Equations (PDEs) of large-scale systems is crucial in many scientific and engineering domains such as fluid dynamics, weather forecasting and their inverse optimization problems.…

Machine Learning · Computer Science 2022-10-13 Tailin Wu , Takashi Maruyama , Jure Leskovec

Neurons exhibit intricate geometries within their neurite networks, which play a crucial role in processes such as signaling and nutrient transport. Accurate simulation of material transport in the networks is essential for understanding…

Machine Learning · Computer Science 2025-07-16 Tsung Yeh Hsieh , Yongjie Jessica Zhang

Predicting cellular responses to various perturbations is a critical focus in drug discovery and personalized therapeutics, with deep learning models playing a significant role in this endeavor. Single-cell datasets contain technical…

Machine Learning · Computer Science 2024-09-11 Seungheun Baek , Soyon Park , Yan Ting Chok , Junhyun Lee , Jueon Park , Mogan Gim , Jaewoo Kang

Single-cell RNA sequencing (scRNA-seq), especially temporally resolved datasets, enables genome-wide profiling of gene expression dynamics at single-cell resolution across discrete time points. However, current technologies provide only…

Genomics · Quantitative Biology 2025-11-19 Yue Ling , Peiqi Zhang , Zhenyi Zhang , Peijie Zhou
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