用于预测转录因子结合位点的多尺度融合特征的新型双注意力深度神经网络
IEEE journal of biomedical and health informatics
|September 1, 2025
概括
通过融合DNA序列和形状特征,DeepCTMS可以准确预测转录因子结合点 (TFBS). 这种新型的深度学习模型提高了药物发现和疾病治疗的基因调控洞察力.
科学领域:
- 基因组学
- 生物信息学
- 计算生物学
背景情况:
- 转录对于基因调节至关重要,涉及转录因子 (TFs) 与特定的DNA位点 (TFBSs) 结合.
- 精确的TFBS预测有助于理解基因表达,促进药物发现和疾病治疗策略.
- 目前用于TFBS预测的深度学习模型往往忽略了DNA的双螺旋结构和3D形状信息.
研究的目的:
- 推出一个新的深度学习模型DeepCTMS,用于增强TFBS预测.
- 有效地整合DNA序列和3D形状特征以获得更高质量的TFBS表示.
- 解决有关DNA结构信息的现有模型的局限性.
主要方法:
- 开发了DeepCTMS模型,该模型融合了DNA片的序列和形状特征.
- 使用序列特征处理模块捕获DNA双螺旋结构.
- 使用卷积三重注意 (CTA) 模块提取3D DNA形状特征.
- 集成了一个多尺度融合特征处理 (MSFFP) 模块,用于语义特征对齐.
主要成果:
- DeepCTMS有效地融合了序列和形状特征,为TFBS预测提供了卓越的表示.
- 废弃实验证实了DeepCTMS中的单个模块的贡献.
- t-SNE可视化支持该模型能够导出有意义的特征表示.
- 对165个ChIP-seq数据集的跨细胞线验证显示出强大的预测性能和概括性.
结论:
- 在TFBS预测准确性方面,DeepCTMS显著优于现有的基准模型.
- 该模型能够整合多种DNA特征,从而提高预测性能和概括性.
- 深度CTMS为促进基因调节和治疗开发的研究提供了一个有前途的工具.
相关概念视频
Transcription Factors
76.7K
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...
76.7K
Cooperative Binding of Transcription Regulators
6.5K
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...
6.5K
General Transcription Factors
5.5K
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...
5.5K
Master Transcription Regulators
7.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.0K
Conserved Binding Sites
4.3K
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...
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...
4.3K
RNA Polymerase II Accessory Proteins
9.4K
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...
9.4K


