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Emerging single-cell technologies that integrate CRISPR-based genetic perturbations with single-cell RNA sequencing, such as Perturb-seq, have substantially advanced our understanding of gene regulation and causal influence of genes. While…

Methodology · Statistics 2026-02-03 Kwangmoon Park , Hongzhe Li

Genomic studies face a vast hypothesis space, while interventions such as gene perturbations remain costly and time-consuming. To accelerate such experiments, gene perturbation models predict the transcriptional outcome of interventions.…

Quantitative Methods · Quantitative Biology 2025-10-21 George Panagopoulos , Johannes F. Lutzeyer , Sofiane Ennadir , Michalis Vazirgiannis , Jun Pang

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

Stem cells can precisely and robustly undergo cellular differentiation and lineage commitment, referred to as stemness. However, how the gene network underlying stemness regulation reliably specifies cell fates is not well understood. To…

Molecular Networks · Quantitative Biology 2020-04-02 Bin Huang , Mingyang Lu , Madeline Galbraith , Herbert Levine , Jose N. Onuchic , Dongya Jia

Reconstructing the causal network in a complex dynamical system plays a crucial role in many applications, from sub-cellular biology to economic systems. Here we focus on inferring gene regulation networks (GRNs) from perturbation or gene…

Quantitative Methods · Quantitative Biology 2016-12-21 Hoi-To Wai , Anna Scaglione , Uzi Harush , Baruch Barzel , Amir Leshem

Learning the response of single-cells to various treatments offers great potential to enable targeted therapies. In this context, neural optimal transport (OT) has emerged as a principled methodological framework because it inherently…

Machine Learning · Computer Science 2025-04-14 Alice Driessen , Benedek Harsanyi , Marianna Rapsomaniki , Jannis Born

Predicting the responses of a cell under perturbations may bring important benefits to drug discovery and personalized therapeutics. In this work, we propose a novel graph variational Bayesian causal inference framework to predict a cell's…

Predicting how a cell will change its transcriptional state under a developmental signal or a genetic perturbation is the computational core of in-silico biology and the AI Virtual Cell program. Existing approaches either fit static…

Machine Learning · Computer Science 2026-05-28 Mufan Qiu , Genhui Zheng , Yinuo Xu , Ruichen Zhang , Ying Ding , Qi Long , Tianlong Chen

Constructing valid and informative conformal prediction regions for multi-dimensional outputs remains a fundamental challenge. While conformal prediction provides finite-sample, distribution-free coverage guarantees, its practical…

Machine Learning · Statistics 2026-05-11 Zhenhan Fang , Aixin Tan , Jian Huang

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

Networks (graphs) in psychology are often restricted to settings without interventions. Here we consider a framework borrowed from biology that involves multiple interventions from different contexts (observations and experiments) in a…

Methodology · Statistics 2024-09-23 Lourens Waldorp , Jolanda Kossakowski , Han L. J. van der Maas

Inferring gene regulatory networks (GRNs) from single-cell RNA sequencing (scRNA-seq) data is a complex challenge that requires capturing the intricate relationships between genes and their regulatory interactions. In this study, we tackle…

Machine Learning · Computer Science 2024-07-26 Sindhura Kommu , Yizhi Wang , Yue Wang , Xuan Wang

The integration of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) data is crucial for understanding gene expression in spatial context. Existing methods for such integration have limited performance, with structural…

Computer Vision and Pattern Recognition · Computer Science 2025-02-12 Rabeya Tus Sadia , Md Atik Ahamed , Qiang Cheng

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

Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction…

Machine Learning · Statistics 2015-06-18 Ali Shojaie , Alexandra Jauhiainen , Michael Kallitsis , George Michailidis

Gene regulatory networks (GRNs) play a crucial role in the control of cellular functions. Numerous methods have been developed to infer GRNs from gene expression data, including mechanism-based approaches, information-based approaches, and…

Molecular Networks · Quantitative Biology 2025-05-16 Xueying Tian , Yash Patel , Yue Wang

Systematic characterization of biological effects to genetic perturbation is essential to the application of molecular biology and biomedicine. However, the experimental exhaustion of genetic perturbations on the genome-wide scale is…

Genomics · Quantitative Biology 2024-03-06 Lingmin Zhan , Yuanyuan Zhang , Yingdong Wang , Aoyi Wang , Caiping Cheng , Jinzhong Zhao , Wuxia Zhang , Peng Lia , Jianxin Chen

It is now possible to conduct large scale perturbation screens with complex readout modalities, such as different molecular profiles or high content cell images. While these open the way for systematic dissection of causal cell circuits,…

Genomics · Quantitative Biology 2025-01-27 Jayoung Ryu , Charlotte Bunne , Luca Pinello , Aviv Regev , Romain Lopez

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

Accurately modeling the relationship between perturbations, transcriptional responses, and phenotypic changes is essential for building an AI Virtual Cell (AIVC). However, existing methods typically constrained to modeling direct…

Machine Learning · Computer Science 2025-11-25 Rui Peng , Ziru Liu , Lingyuan Ye , Yuxing Lu , Boxin Shi , Jinzhuo Wang