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. 2023 Nov 8;13:19371. doi: 10.1038/s41598-023-46295-6

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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SIGNET workflow for gene regulatory network (GRN) construction. SIGNET takes four steps to conduct causal inference and construct a GRN from transcriptomic and genotypic data: 1. Preprocessing transcriptomic and genotypic data to ensure data quality; 2. Identifying genotypic instrumental variables; 3. Constructing a transcriptome-wide GRN via causal inference; 4. Visualizing subnetworks of the GRN and validating with public databases.