在成像转录学中对背景基因遗漏的批判性评估
Zhipeng Cao1,2, Li Bao1, Jinmei Qin1
1Shanghai Xuhui Mental Health Center, Shanghai, China.
Biological psychiatry global open science
|September 2, 2025
概括
在成像转录学中,适当的背景基因选择对于准确的过度表示分析 (ORA) 是至关重要的. 使用适当的背景,如艾伦人类大脑图谱 (AHBA) 基因,可以防止基因组丰富性分析中的夸张意义.
科学领域:
- 神经科学
- 基因组学
- 生物信息学
背景情况:
- 图像转录学将脑成像表型与基因表达联系起来.
- 过度表现分析 (ORA) 常用于解释与成像衍生的表型 (IDP) 相关的基因组.
- 之前的研究往往忽略了ORA的适当基因选择.
研究的目的:
- 评估背景基因选择对ORA成像转录学结果的影响.
- 评估已发表的成像转录学研究中适当的背景报告的普遍性.
- 提供有关选择合适的ORA背景的指导.
主要方法:
- 对152个成像转录学研究的系统审查 (2015-2024年).
- 模拟以评估背景大小对ORA显著性的影响.
- 使用不同背景基因组 (例如所有蛋白质编码基因与AHBA基因) 的ORA结果比较.
主要成果:
- 在审查的研究中,84. 9% 没有报告ORA的背景基因.
- 只有5. 26%的研究使用了艾伦人类大脑图谱 (AHBA) 基因组作为背景.
- 默认背景显著增加了路径显著性 (高达50倍),而AHBA背景保持了接近0.05的显著性.
结论:
- 不适当的背景选择会在成像转录组学中增加ORA的发现,特别是对于突触和神经传递通路.
- 使用AHBA基因组为ORA提供了更可靠的背景.
- 对背景基因选择的透明报告对于成像转录组学研究的有效性至关重要.
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