20.500.12556/DiRROS-19372 Controlling gene expression with deep generative design of regulatory DNA Design of de novo synthetic regulatory DNA is a promising avenue to control gene expression in biotechnology and medicine. Using mutagenesis typically requires screening sizable random DNA libraries, which limits the designs to span merely a short section of the promoter and restricts their control of gene expression. Here, we prototype a deep learning strategy based on generative adversarial networks (GAN) by learning directly from genomic and transcriptomic data. Our ExpressionGAN can traverse the entire regulatory sequence-expression landscape in a gene-specific manner, generating regulatory DNA with prespecified target mRNA levels spanning the whole gene regulatory structure including coding and adjacent non-coding regions. Despite high sequence divergence from natural DNA, in vivo measurements show that 57% of the highly-expressed synthetic sequences surpass the expression levels of highly-expressed natural controls. This demonstrates the applicability and relevance of deep generative design to expand our knowledge and control of gene expression regulation in any desired organism, condition or tissue. biokemija izražanje genov bioinformatika globoko učenje sintetična biologija true false true Angleški jezik Slovenski jezik Neznano 2024-07-17 03:55:21 2024-07-17 10:17:34 2024-07-18 03:53:59 0000-00-00 00:00:00 2022 0 0 Nasl. z nasl. zaslona; Opis vira z dne 5. 9. 2022; Št. članka: 5099; str. 1-17 Vol. 13 30 Aug. 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2022-08-30 577 2041-1723 10.1038/s41467-022-32818-8 120155139 https://www.nature.com/articles/s41467-022-32818-8 1 dcaf2b80-43ce-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26737 RAZ_Zrimec_Jan_2022.pdf RAZ_Zrimec_Jan_2022.pdf 1 00A03BAB7CA3E0332CD9DB73C1ED1A90 a4d88f194c7efd90024c0f6f607fe1046fb9fb58dd856b1f0617dd41b80ca2fe a1b1c07c-4405-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26825 Nacionalni inštitut za biologijo 0 0 0