用深度学习剖析转录启动的cis调控语法
Kelly Cochran1, Melody Yin2, Anika Mantripragada2
1Department of Computer Science, Stanford University, Stanford, CA, USA.
bioRxiv : the preprint server for biology
|June 10, 2024
概括
一个新的神经网络,ProCapNet,破译了DNA序列规则,控制了人类促进器和增强器的转录启动. 它揭示了共享的监管逻辑和复杂的动机相互作用,提高了预测准确性.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 哺乳动物RNA聚合酶II (Pol II) 转录启动对于基因调节至关重要.
- 在许多人类促进剂和增强剂中启动的DNA序列决定因素尚未完全理解.
研究的目的:
- 根据DNA序列开发一个计算模型来预测基于DNA序列的转录启动配置文件.
- 揭示序列动机和监管逻辑,管理在人类促进器和增强剂的启动.
主要方法:
- 在PRO-cap实验中的基础分辨率启动配置文件上训练一个神经网络 (ProCapNet).
- 解释ProCapNet以识别序列动机及其对启动率和转录开始地点 (TSS) 定位的影响.
- 应用ProCapNet来建模RAMPAGE配置文件和注释监管元素.
主要成果:
- ProCapNet使用本地DNA序列准确地建模启动配置文件.
- 确定了序列图案,在启动速率和TSS定位方面发挥了特定的作用.
- 揭示了特定于背景的神秘启动元件和动机之间的复杂的,表观性相互作用.
- 在促进者和增强剂之间揭示了一个共享的cis-regulatory逻辑.
- 证明了ProCapNet从RAMPAGE数据中建模启动信号的能力,与PRO-cap数据相比.
结论:
- ProCapNet提供了一个强大的工具,用于理解转录启动的cis-regulatory代码.
- 这项研究揭示了一种基本上与细胞类型无关的序列代码,用于启动,补充细胞类型特定的染色质状态.
- 这些发现增强了对细胞类型特定转录启动的预测.
相关概念视频
02:02Cis-regulatory Sequences
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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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01:47Transcription Initiation
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02:36RNA Polymerase II Accessory Proteins
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01:23Regulation of Expression at Multiple Steps
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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