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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

In this work, we introduce a novel computational framework that we developed to use numerical simulations to investigate the complexity of brain tissue at a microscopic level with a detail never realised before. Directly inspired by the…

Medical Physics · Physics 2018-06-20 Marco Palombo , Daniel C. Alexander , Hui Zhang

Perturbation screens hold the potential to systematically map regulatory processes at single-cell resolution, yet modeling and predicting transcriptome-wide responses to perturbations remains a major computational challenge. Existing…

Molecular Networks · Quantitative Biology 2026-01-26 Lars Lorch , Jiaqi Zhang , Charlotte Bunne , Andreas Krause , Bernhard Schölkopf , Caroline Uhler

Single-cell data provide high-dimensional measurements of the transcriptional states of cells, but extracting insights into the regulatory functions of genes, particularly identifying transcriptional mechanisms affected by biological…

Molecular Networks · Quantitative Biology 2025-03-27 Paul Bertin , Joseph D. Viviano , Alejandro Tejada-Lapuerta , Weixu Wang , Stefan Bauer , Fabian J. Theis , Yoshua Bengio

We train a neural network to predict distributional responses in gene expression following genetic perturbations. This is an essential task in early-stage drug discovery, where such responses can offer insights into gene function and inform…

Cell identity encompasses various semantic aspects of a cell, including cell type, pathway information, disease information, and more, which are essential for biologists to gain insights into its biological characteristics. Understanding…

Genomics · Quantitative Biology 2024-06-12 Suyuan Zhao , Jiahuan Zhang , Yushuai Wu , Yizhen Luo , Zaiqing Nie

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

Drug discovery is fundamentally a process of inferring the effects of treatments on patients, and would therefore benefit immensely from computational models that can reliably simulate patient responses, enabling researchers to generate and…

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

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…

In order to understand the complexities of cellular biology, researchers are interested in two important metrics: the genetic expression information of cells and their spatial coordinates within a tissue sample. However, state-of-the art…

Machine Learning · Computer Science 2023-11-02 J. Ding , S. N. Zaman , P. Y. Chen , D. Wang

We propose a probabilistic model for interpreting gene expression levels that are observed through single-cell RNA sequencing. In the model, each cell has a low-dimensional latent representation. Additional latent variables account for…

Machine Learning · Computer Science 2017-10-18 Romain Lopez , Jeffrey Regier , Michael Cole , Michael Jordan , Nir Yosef

Spatial transcriptomics methods capture cellular measurements such as gene expression and cell types at specific locations in a cell, helping provide a localized picture of tissue health. Traditional visualization techniques superimpose the…

Quantitative Methods · Quantitative Biology 2024-10-16 Siyuan Zhao , G. Elisabeta Marai

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by…

Traditional molecule generation methods often rely on sequence- or graph-based representations, which can limit their expressive power or require complex permutation-equivariant architectures. This paper introduces a novel paradigm for…

Machine Learning · Computer Science 2025-02-18 Van Khoa Nguyen , Maciej Falkiewicz , Giangiacomo Mercatali , Alexandros Kalousis

Advances in single-cell omics allow for unprecedented insights into the transcription profiles of individual cells. When combined with large-scale perturbation screens, through which specific biological mechanisms can be targeted, these…

Machine Learning · Computer Science 2023-10-24 Alejandro Tejada-Lapuerta , Paul Bertin , Stefan Bauer , Hananeh Aliee , Yoshua Bengio , Fabian J. Theis

Microscopy-based phenotypic profiling is scalable for drug discovery but lacks the mechanistic depth of transcriptomics, which remains costly and scarce. Existing multimodal approaches either use images to support other modalities or…

Computer Vision and Pattern Recognition · Computer Science 2026-04-28 Jiayuan Chen , Ruoqi Liu , Zishan Gu , Ping Zhang

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…

Large-scale cell microscopy screens are used in drug discovery and molecular biology research to study the effects of millions of chemical and genetic perturbations on cells. To use these images in downstream analysis, we need models that…

The development of single-cell and spatial transcriptomics has revolutionized our capacity to investigate cellular properties, functions, and interactions in both cellular and spatial contexts. However, the analysis of single-cell and…

Genomics · Quantitative Biology 2024-12-09 Shuang Ge , Shuqing Sun , Huan Xu , Qiang Cheng , Zhixiang Ren
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