基因组序列到活动模型预测中的不确定性
Ayesha Bajwa1, Ruchir Rastogi1, Pooja Kathail2
1Department of Electrical Engineering and Computer Sciences, University of California Berkeley, Berkeley, CA, USA.
bioRxiv : the preprint server for biology
|January 8, 2024
概括
基因组序列到活动模型对参考基因组具有很高的信心,但准确性较低. 这些模型与遗传变异作斗争,对eQTL和个人基因组产生不一致的预测.
科学领域:
- 基因组学就是基因组学.
- 计算生物学 计算生物学
- 生物信息学是一种生物信息学.
背景情况:
- 基因组序列到活性模型预测基因调节功能和遗传变异的影响.
- 目前的模型准确地预测了人类参考基因组上的活动,但对个体遗传变异和基因表达不那么有效.
- 了解这些模型的局限性对于推进遗传研究和个性化医学至关重要.
研究的目的:
- 研究基因组序列到活动模型的预测不确定性,特别是Basenji2模型.
- 评估不同序列类型的模型性能一致性,包括参考基因组,扰乱序列,eQTL和个人基因组.
- 确定导致模型缺陷的因素,以预测遗传变异的功能影响.
主要方法:
- 利用Basenji2模型复制组合来评估预测的一致性.
- 分析了四种不同的序列类型的模型性能:参考基因组,具有TF动机的参考基因组,eQTL和个人基因组.
- 在这些序列类别中量化预测的信心和一致性.
主要成果:
- 基因组序列到活动模型具有很高的可靠性,但在参考序列上可能不准确.
- 模型在预测含有遗传变异的序列的影响时显示出低信心和高不一致性.
- 模型复制产生不一致的预测超过50%的eQTL和个人基因组序列.
- 与参考序列相比,具有遗传变异的序列的预测不确定性显著更高.
结论:
- 目前的基因组序列到活动模型需要改进,以准确预测遗传变异的功能影响.
- 模型信心并不总是与预测准确性相关,尤其是在非参考序列上.
- 解决模型中的预测不确定性对于可靠地解释监管变异和个性化基因组学至关重要.
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