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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

Building Virtual Cells that can accurately simulate cellular responses to perturbations is a long-standing goal in systems biology. A fundamental challenge is that high-throughput single-cell sequencing is destructive: the same cell cannot…

Machine Learning · Computer Science 2026-02-24 Xinyu Yuan , Xixian Liu , Ya Shi Zhang , Zuobai Zhang , Hongyu Guo , Jian Tang

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

Phenotype-based screening has attracted much attention for identifying cell-active compounds. Transcriptional and proteomic profiles of cell population or single cells are informative phenotypic measures of cellular responses to…

Quantitative Methods · Quantitative Biology 2023-11-20 Wei Huang , Aichun Zhu , Hui Liu

Drug resistance presents a major challenge in cancer therapy. Single cell profiling offers insights into cellular heterogeneity, yet the application of large-scale foundation models for predicting drug response in single cell data remains…

Artificial Intelligence · Computer Science 2025-05-12 Qing Wang , Yining Pan , Minghao Zhou , Zijia Tang , Yanfei Wang , Guangyu Wang , Qianqian Song

The rise of single-cell sequencing technologies has revolutionized the exploration of drug resistance, revealing the crucial role of cellular heterogeneity in advancing precision medicine. By building computational models from existing…

Genomics · Quantitative Biology 2025-02-05 Yu-An Huang , Xiyue Cao , Zhu-Hong You , Yue-Chao Li , Xuequn Shang , Zhi-An Huang

Survival analysis aims to estimate a time-to-event distribution from data with censored observations. Many existing methods either impose structural assumptions on the hazard function or discretize the time axis, which may limit flexibility…

Machine Learning · Computer Science 2026-05-22 Stanislav R. Kirpichenko , Andrei V. Konstantinov , Lev V. Utkin

Single-cell RNA sequencing (scRNA-seq) data are important for studying the laws of life at single-cell level. However, it is still challenging to obtain enough high-quality scRNA-seq data. To mitigate the limited availability of data,…

Quantitative Methods · Quantitative Biology 2024-03-06 Erpai Luo , Minsheng Hao , Lei Wei , Xuegong Zhang

Influenced by breakthroughs in LLMs, single-cell foundation models are emerging. While these models show successful performance in cell type clustering, phenotype classification, and gene perturbation response prediction, it remains to be…

AI-driven drug response prediction holds great promise for advancing personalized cancer treatment. However, the inherent heterogenity of cancer and high cost of data generation make accurate prediction challenging. In this study, we…

Machine Learning · Computer Science 2025-05-14 Till Rossner , Ziteng Li , Jonas Balke , Nikoo Salehfard , Tom Seifert , Ming Tang

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 transcriptional responses to novel drugs provides a unique opportunity to accelerate biomedical research and advance drug discovery efforts. However, the inherent complexity and high dimensionality of cellular responses, combined…

Single-cell RNA sequencing (scRNA-seq) technology has profiled hundreds of millions of human cells across organs, diseases, development and perturbations to date. However, the high-dimensional sparsity, batch effect noise, category…

Machine Learning · Computer Science 2025-03-07 Zhen Yu , Jianan Han , Yang Liu , Qingchao Chen

The single-cell RNA sequencing (scRNA-seq) technology enables researchers to study complex biological systems and diseases with high resolution. The central challenge is synthesizing enough scRNA-seq samples; insufficient samples can impede…

Genomics · Quantitative Biology 2023-12-25 Yixuan Wang , Shuangyin Li , Shimin DI , Lei Chen

The advancement of single-cell sequencing technology has promoted the generation of a large amount of single-cell transcriptional profiles, providing unprecedented opportunities to identify drug-resistant cell subpopulations within a tumor.…

Artificial Intelligence · Computer Science 2025-01-08 Hui Liu , Wei Duan , Judong Luo

Generating high-fidelity and biologically plausible synthetic single-cell RNA sequencing (scRNA-seq) data, especially with conditional control, is challenging due to its high dimensionality, sparsity, and complex biological variations.…

Machine Learning · Computer Science 2025-06-17 Lorenzo Bini , Stephane Marchand-Maillet

Computational modeling of single-cell gene expression is crucial for understanding cellular processes, but generating realistic expression profiles remains a major challenge. This difficulty arises from the count nature of gene expression…

Estimating single-cell responses across various perturbations facilitates the identification of key genes and enhances drug screening, significantly boosting experimental efficiency. However, single-cell sequencing is a destructive process,…

Machine Learning · Computer Science 2026-04-28 Changxi Chi , Jun Xia , Yufei Huang , Zhuoli Ouyang , Cheng Tan , Yunfan Liu , Jingbo Zhou , Chang Yu , Liangyu Yuan , Siyuan Li , Zelin Zang , Stan Z. Li

Motivation: Single-cell RNA sequencing (scRNA-seq) is a groundbreaking technology extensively utilized in biological research, facilitating the examination of gene expression at the individual cell level within a given tissue sample. While…

Machine Learning · Computer Science 2024-04-10 Shengze Dong , Zhuorui Cui , Ding Liu , Jinzhi Lei

Diffusion models have shown promise in forecasting future data from multivariate time series. However, few existing methods account for recurring structures, or patterns, that appear within the data. We present Pattern-Guided Diffusion…

Machine Learning · Computer Science 2025-12-17 Vivian Lin , Kuk Jin Jang , Wenwen Si , Insup Lee
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