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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 with generative models to simulate cellular behavior in silico is emerging as a promising paradigm for accelerating drug discovery. However, prior image-based generative approaches can produce implausible cell images…

Machine Learning · Computer Science 2026-05-22 Dongxia Wu , Shiye Su , Yuhui Zhang , Elaine Sui , Emma Lundberg , Emily B. Fox , Serena Yeung-Levy

Many modern biological assays, including RNA sequencing, yield integer-valued counts that reflect the number of molecules detected. These measurements are often not at the desired resolution: while the unit of interest is typically a single…

Machine Learning · Computer Science 2026-03-06 Nic Fishman , Gokul Gowri , Tanush Kumar , Jiaqi Lu , Valentin de Bortoli , Jonathan S. Gootenberg , Omar Abudayyeh

The segmentation of cell nuclei in tissue images stained with the blood dye hematoxylin and eosin (H$\&$E) is essential for various clinical applications and analyses. Due to the complex characteristics of cellular morphology, a large…

Image and Video Processing · Electrical Eng. & Systems 2024-07-26 Ziwei Cui , Jingfeng Yao , Lunbin Zeng , Juan Yang , Wenyu Liu , Xinggang Wang

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

Drug discovery is a complex process that involves multiple stages and tasks. However, existing molecular generative models can only tackle some of these tasks. We present Generalist Molecular generative model (GenMol), a versatile framework…

Machine Learning · Computer Science 2025-07-24 Seul Lee , Karsten Kreis , Srimukh Prasad Veccham , Meng Liu , Danny Reidenbach , Yuxing Peng , Saee Paliwal , Weili Nie , Arash Vahdat

Spatial transcriptomics measures the expression of thousands of genes in a tissue sample while preserving its spatial structure. This class of technologies has enabled the investigation of the spatial variation of gene expressions and their…

Methodology · Statistics 2025-10-23 Andrea Sottosanti , Davide Risso , Francesco Denti

Predicting the effects of chemical and genetic perturbations on quantitative cell states is a central challenge in computational biology, molecular medicine and drug discovery. Recent work has leveraged large-scale single-cell data and…

Machine Learning · Computer Science 2026-03-16 Michael Scholkemper , Sach Mukherjee

Cellular response to a perturbation is the result of a dynamic system of biological variables linked in a complex network. A major challenge in drug and disease studies is identifying the key factors of a biological network that are…

Applications · Statistics 2014-09-02 Lisa M. Pham , Luis Carvalho , Scott Schaus , Eric D. Kolaczyk

Feedback in cellular processes is typically inferred through cellular responses to experimental perturbations. Modular response analysis provides a theoretical framework for translating specific perturbations into feedback sensitivities…

Molecular Networks · Quantitative Biology 2025-05-09 Seshu Iyengar , Andreas Hilfinger

Deep generative models have significantly advanced medical imaging analysis by enhancing dataset size and quality. Beyond mere data augmentation, our research in this paper highlights an additional, significant capacity of deep generative…

Computer Vision and Pattern Recognition · Computer Science 2024-10-18 Xiaodan Xing , Junzhi Ning , Yang Nan , Guang Yang

The fundamental understanding of how cells physically interact with each other and their environment is key to understanding their organisation in living tissues. Over the past decades several computational methods have been developed to…

Quantitative Methods · Quantitative Biology 2026-01-22 Paul Van Liedekerke , Jiří Pešek , Kevin Alessandri , Dirk Drasdo

A generative modeling framework is proposed that combines diffusion models and manifold learning to efficiently sample data densities on manifolds. The approach utilizes Diffusion Maps to uncover possible low-dimensional underlying (latent)…

Machine Learning · Computer Science 2025-04-22 Dimitris G. Giovanis , Ellis Crabtree , Roger G. Ghanem , Ioannis G. Kevrekidis

Cells regulate themselves via dizzyingly complex biochemical processes called signaling pathways. These are usually depicted as a network, where nodes represent proteins and edges indicate their influence on each other. In order to…

Molecular Networks · Quantitative Biology 2021-01-13 David Merrell , Anthony Gitter

Despite the central role of sensor-derived measurements such as imaging traits and plasma biomarkers in biomedical research and clinical practice, existing generative models for disease prediction largely depend on event-level…

Artificial Intelligence · Computer Science 2026-05-12 Ziquan Wei , Tingting Dan , Guorong Wu

Self-supervised learning (SSL) has been successful in building patch embeddings of small histology images (e.g., 224x224 pixels), but scaling these models to learn slide embeddings from the entirety of giga-pixel whole-slide images (WSIs)…

Computer Vision and Pattern Recognition · Computer Science 2024-05-21 Guillaume Jaume , Lukas Oldenburg , Anurag Vaidya , Richard J. Chen , Drew F. K. Williamson , Thomas Peeters , Andrew H. Song , Faisal Mahmood

Signal-processing molecules inside cells are often present at low copy number, which necessitates probabilistic models to account for intrinsic noise. Probability distributions have traditionally been found using simulation-based approaches…

Molecular Networks · Quantitative Biology 2009-11-09 Andrew Mugler , Aleksandra M. Walczak , Chris H. Wiggins

This paper presents a novel approach that leverages domain variability to learn representations that are conditionally invariant to unwanted variability or distractors. Our approach identifies both spurious and invariant latent features…

Machine Learning · Computer Science 2023-07-04 Hananeh Aliee , Ferdinand Kapl , Soroor Hediyeh-Zadeh , Fabian J. Theis

Cells of the human body have nearly identical genome but exhibit very different phenotypes that allow them to carry out specific functions and react to changes in their surrounding environment. This division of labour is achieved by…

Cell Behavior · Quantitative Biology 2021-11-24 Hanan Dreiwi , Flavia Feliciangeli , Mario Castro , Grant Lythe , Carmen Molina-París , Martín López-García

Live cell microscopy sequences exhibit complex spatial structures and complicated temporal behaviour, making their analysis a challenging task. Considering cell segmentation problem, which plays a significant role in the analysis, the…

Computer Vision and Pattern Recognition · Computer Science 2019-01-08 Assaf Arbelle , Tammy Riklin Raviv