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相关概念视频

Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Conserved Binding Sites01:49

Conserved Binding Sites

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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
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Cis-regulatory Sequences02:02

Cis-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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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
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通过深度学习对低亲和度转录因子-DNA结合的基于序列建模.

Yingfei Wang1, Jinsen Li1, Tsu-Pei Chiu1

  • 1Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, United States.

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概括

反向补充重量共享模型提高了深度学习的准确性,用于预测转录因子-DNA结合特异性,特别是在低亲和度位点. 这一进步有助于理解基因调节和蛋白质设计.

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科学领域:

  • 计算生物学是一种计算生物学.
  • 基因组学就是基因组学.
  • 分子生物学分子生物学

背景情况:

  • 转录因子-DNA结合特异性对于基因调节至关重要.
  • 包括CNN和SA变压器在内的深度学习模型已经进行了先进的TF-DNA结合预测.
  • 需要对模型中的DNA序列定向处理进行系统的评估,特别是对于低亲和度结合.

研究的目的:

  • 为了比较处理TF-DNA结合特异性的深度学习模型中的DNA序列定向的不同策略.
  • 评估这些模型的解释方法.
  • 识别低亲和度结合点及其机制.

主要方法:

  • 使用SELEX-seq数据对Drosophila中的八个Exd-Hox异构体进行了分析.
  • 将正规模型与数据增强和反向补充重量分配模型 (CNN和SA变压器) 进行比较.
  • 评估的解释方法:渐变输入,DeconvNet,DeepLIFT,以及在基变异 (ISM).

主要成果:

  • 用增强数据训练的反补充重量共享CNN和SA模型的表现优于其他方法.
  • 与其他解释方法相比,in silico mutagenesis (ISM) 对超参数设置的敏感性较小.
  • 在低亲和度位点确定了Exd-Ubx结合,并提出了生物物理机制.

结论:

  • 反向补充策略增强了TF-DNA结合特异性的深度学习模型,特别是对于低亲和度相互作用.
  • 对于这些模型来说,ISM是一种强大的解释方法.
  • 这些发现有助于理解基因调节中的低亲缘关系TF结合,并为TF-DNA结合特异性引导的蛋白质设计提供信息.