Transcription initiation is a process that is essential to ensuring the proper function of any gene, yet we still lack a unified understanding of sequence patterns and rules that explain most transcription start sites in the human genome. By predicting transcription initiation at base-pair resolution from sequences with a deep learning–inspired explainable model called Puffin, we show that a small set of simple rules can explain transcription initiation at most human promoters. We identify key sequence patterns that contribute to human promoter activity, each activating transcription with distinct position-specific effects. Furthermore, we explain the sequence basis of bidirectional transcription at promoters, identify the links between promoter sequence and gene expression variation across cell types, and explore the conservation of sequence determinants of transcription initiation across mammalian species.

中文翻译：

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人类基因组转录起始的序列基础

转录起始是确保任何基因正常功能所必需的过程，但我们仍然缺乏对解释人类基因组中大多数转录起始位点的序列模式和规则的统一理解。通过使用受深度学习启发的可解释模型 Puffin 来预测序列中碱基对分辨率的转录起始，我们表明一小组简单的规则可以解释大多数人类启动子的转录起始。我们确定了有助于人类启动子活性的关键序列模式，每种激活转录都具有不同的位置特异性效应。此外，我们解释了启动子双向转录的序列基础，确定了启动子序列与跨细胞类型的基因表达变异之间的联系，并探索了跨哺乳动物物种转录起始的序列决定因素的保守性。