用注意力模型破解基因型到表型的复杂关系,预测更准。
Inferring genotype-phenotype maps using attention models
- 引入注意力机制捕捉基因间的非线性互作
- 在多重上位性场景下,预测准确率显著优于传统方法
- 可跨环境迁移学习,少样本下仍有效
从基因型预测表型是遗传学的核心挑战。传统数量遗传学多采用基于线性回归的方法,通常假设复杂性状的遗传架构可由独立加性效应及部分双基因互作(上位性)描述。然而这些模型难以处理复杂的上位性或细微的基因-环境互作。近年来,以注意力机制为代表的机器学习方法展现出强大潜力,尤其在蛋白质结构与功能预测中表现优异。本文将注意力模型应用于数量遗传学,通过模拟数据(涵盖不同上位性复杂度)和酿酒酵母的定量性状位点研究实验数据,验证其性能。结果表明,在存在复杂上位性的条件下,该模型在外部样本上的预测表现显著优于标准方法。此外,我们构建了多环境注意力模型,实现跨环境联合分析,并验证其可用于“迁移学习”——在新环境中仅用少量训练数据即可预测表型。
原文摘要 · Abstract (English)
Predicting phenotype from genotype is a central challenge in genetics. Traditional approaches in quantitative genetics typically analyze this problem using methods based on linear regression. These methods generally assume that the genetic architecture of complex traits can be parameterized in terms of an additive model, where the effects of loci are independent, plus (in some cases) pairwise epistatic interactions between loci. However, these models struggle to analyze more complex patterns of epistasis or subtle gene-environment interactions. Recent advances in machine learning, particularly attention-based models, offer a promising alternative. Initially developed for natural language processing, attention-based models excel at capturing context-dependent interactions and have shown exceptional performance in predicting protein structure and function. Here, we apply attention-based models to quantitative genetics. We analyze the performance of this attention-based approach in predicting phenotype from genotype using simulated data across a range of models with increasing epistatic complexity, and using experimental data from a recent quantitative trait locus mapping study in budding yeast. We find that our model demonstrates superior out-of-sample predictions in epistatic regimes compared to standard methods. We also explore a more general multi-environment attention-based model to jointly analyze genotype-phenotype maps across multiple environments and show that such architectures can be used for "transfer learning" - predicting phenotypes in novel environments with limited training data.
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