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Large-scale causal discovery using interventional data sheds light on gene network structure in k562 cells
Division of Informatics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA; Department of Computer Science, University of Pennsylvania, Philadelphia, PA, USA.
New York Genome Center, New York, NY, USA.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. New York Genome Center, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA.ORCID-id: 0000-0002-7746-8109
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2025 (engelsk)Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 16, nr 1, artikkel-id 9628Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Inference of directed biological networks is an important but notoriously challenging problem. The recent proliferation of large-scale CRISPR perturbation data provides a new opportunity to tackle this problem by leveraging the transcriptional response to the presence of a gene-targeting guide. Here, we introduce inverse sparse regression (inspre), an approach to learning causal networks that leverages large-scale intervention-response data. Applied to 788 genes from the genome-wide perturb-seq dataset, inspre discovers a network with small-world and scale-free properties. We integrate our network estimate with external data, finding relationships between gene eigencentrality and both measures of gene essentiality and gene expression heritability. Our analysis helps to elucidate the structure of networks that may underlie complex traits.

sted, utgiver, år, opplag, sider
Springer Nature , 2025. Vol. 16, nr 1, artikkel-id 9628
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URN: urn:nbn:se:kth:diva-372897DOI: 10.1038/s41467-025-64353-7ISI: 001606917700015PubMedID: 41173850Scopus ID: 2-s2.0-105020589023OAI: oai:DiVA.org:kth-372897DiVA, id: diva2:2013790
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QC 20251114

Tilgjengelig fra: 2025-11-14 Laget: 2025-11-14 Sist oppdatert: 2025-11-14bibliografisk kontrollert

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