使用全面的地图和预测模型来揭示大脑活性调节元件的复杂性和演变
Henry E Pratt1, Gregory Andrews1, Nicole Shedd1
1Department of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Science advances
|May 23, 2024
概括
研究人员绘制了与精神疾病相关的大脑调节元件的地图,揭示了新的遗传信息来自于保存序列中的突变. 灵长类动物特有的元素对于胎儿大脑发育和人类特征至关重要.
科学领域:
- 基因组学和神经生物学
- 计算生物学和生物信息学
背景情况:
- 大多数精神疾病的遗传变异都存在于非编码DNA中.
- 了解这些非编码变体的功能对于精神疾病研究至关重要.
研究的目的:
- 为了创建一个候选大脑cis-regulatory元素的地图.
- 研究这些元素在细胞类型特定基因调节中的作用.
- 探索调节元件的进化起源及其与精神疾病遗传性的联系.
主要方法:
- 整合了来自PsychENCODE联盟和其他来源的表观遗传数据.
- 深度学习的应用以建模序列语法和预测转录因子结合.
- 对监管要素的进化历史进行分析.
- 介绍了用于数据可视化的PsychSCREEN网络平台.
主要成果:
- 构建了一个关于候选大脑 cis-regulatory 元素的综合图谱.
- 深度学习模型通过转录因子预测了细胞类型特定的基因调节.
- 进化分析表明,新的大脑调节信息来自于保存元素的突变.
- 在胎儿发育和特定神经元/质类型中活跃的灵长类动物特有的元素与人类特征的遗传性有关.
结论:
- 监管因素在精神疾病的遗传结构中发挥着重要作用.
- 进化机制塑造了大脑的调节格局,保留的元素是创新的首要来源.
- 灵长类动物特有的调节元素有助于人类大脑的进化和特征的遗传性.
- 心理学屏幕平台为精神疾病研究提供了有价值的遗传和表观遗传数据.
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