arXiv:2505.22746cs.NEcs.LG2025-05

用进化算法找基因与表型关联,兼顾准确性和简洁性。

StarBASE-GP: Biologically-Guided Automated Machine Learning for Genotype-to-Phenotype Association Analysis

  • 基于遗传编程优化机器学习流程,同时提升预测力和简化结构。
  • 在大鼠数据中识别出高精度的定量性状位点,优于随机基线。
  • 融合生物学知识,适合复杂性状的基因发现研究者使用。

我们提出StarBASE-GP,一种用于大规模基因组数据中基因型到表型关联分析的自动化框架。该方法采用基于遗传编程的多目标优化策略,演化机器学习管道以同时最大化解释力(r²)并最小化模型复杂度。在多个阶段融入生物领域知识:使用九种遗传编码方式模拟非加性效应,设计自定义连锁不平衡剪枝节点减少特征冗余,并构建动态变异推荐系统优先选择有信息量的候选位点。在褐鼠队列中评估该工具对体质量指数相关基因的识别能力,与随机基线及无生物先验版本相比,始终生成更优的帕累托前沿,显著提高对真实和新发现数量性状位点的识别准确率,揭示了未来验证的关键靶点。通过将进化搜索与生物学理论结合,星基自动机器学习框架展现出在复杂性状基因发现中的强大潜力。

原文摘要 · Abstract (English)

We present the Star-Based Automated Single-locus and Epistasis analysis tool - Genetic Programming (StarBASE-GP), an automated framework for discovering meaningful genetic variants associated with phenotypic variation in large-scale genomic datasets. StarBASE-GP uses a genetic programming-based multi-objective optimization strategy to evolve machine learning pipelines that simultaneously maximize explanatory power (r2) and minimize pipeline complexity. Biological domain knowledge is integrated at multiple stages, including the use of nine inheritance encoding strategies to model deviations from additivity, a custom linkage disequilibrium pruning node that minimizes redundancy among features, and a dynamic variant recommendation system that prioritizes informative candidates for pipeline inclusion. We evaluate StarBASE-GP on a cohort of Rattus norvegicus (brown rat) to identify variants associated with body mass index, benchmarking its performance against a random baseline and a biologically naive version of the tool. StarBASE-GP consistently evolves Pareto fronts with superior performance, yielding higher accuracy in identifying both ground truth and novel quantitative trait loci, highlighting relevant targets for future validation. By incorporating evolutionary search and relevant biological theory into a flexible automated machine learning framework, StarBASE-GP demonstrates robust potential for advancing variant discovery in complex traits.

基因关联自动化ML遗传编程生物信息

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