Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China.
Innovation Group of Pig Genome Design and Breeding, Research Centre for Animal Genome, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China.
Biomolecules. 2024 Aug 5;14(8):945. doi: 10.3390/biom14080945.
Cis-regulatory elements (CREs) play a pivotal role in orchestrating interactions with trans-regulatory factors such as transcription factors, RNA-binding proteins, and noncoding RNAs. These interactions are fundamental to the molecular architecture underpinning complex and diverse biological functions in living organisms, facilitating a myriad of sophisticated and dynamic processes. The rapid advancement in the identification and characterization of these regulatory elements has been marked by initiatives such as the Encyclopedia of DNA Elements (ENCODE) project, which represents a significant milestone in the field. Concurrently, the development of CRE detection technologies, exemplified by massively parallel reporter assays, has progressed at an impressive pace, providing powerful tools for CRE discovery. The exponential growth of multimodal functional genomic data has necessitated the application of advanced analytical methods. Deep learning algorithms, particularly large language models, have emerged as invaluable tools for deconstructing the intricate nucleotide sequences governing CRE function. These advancements facilitate precise predictions of CRE activity and enable the de novo design of CREs. A deeper understanding of CRE operational dynamics is crucial for harnessing their versatile regulatory properties. Such insights are instrumental in refining gene therapy techniques, enhancing the efficacy of selective breeding programs, pushing the boundaries of genetic innovation, and opening new possibilities in microbial synthetic biology.
顺式调控元件（CREs）在协调与转录因子、RNA 结合蛋白和非编码 RNA 等反式调控因子的相互作用方面起着关键作用。这些相互作用是构成活生物体中复杂多样的生物功能的分子结构基础，促进了无数复杂和动态的过程。随着识别和表征这些调控元件的计划的推进，如 DNA 元件百科全书（ENCODE）项目，该领域取得了显著的进展。同时，CRE 检测技术的发展，如大规模平行报告基因检测，也取得了令人瞩目的进展，为 CRE 发现提供了强大的工具。多模态功能基因组数据的指数级增长需要应用先进的分析方法。深度学习算法，特别是大型语言模型，已成为解析调控 CRE 功能的复杂核苷酸序列的宝贵工具。这些进展促进了 CRE 活性的精确预测，并能够从头设计 CRE。深入了解 CRE 的操作动态对于利用其多功能的调控特性至关重要。这些见解对于改进基因治疗技术、提高选择性繁殖计划的效率、推动遗传创新的边界以及在微生物合成生物学中开辟新的可能性都具有重要意义。
