用深度学习预测水稻基因变异影响,加速抗逆育种。
AgriVariant: Variant Effect Prediction using DeepChem-Variant for Precision Breeding in Rice
- 结合深度学习与植物基因组注释,构建可扩展的变异预测流程。
- 10天完成1509个单碱基变异分析,识别353个高影响变异。
- 适合育种者快速筛选关键变异,降低实验成本。
预测作物基因变异的功能后果仍是精准育种的关键瓶颈。我们提出AgriVariant,一个针对水稻(Oryza sativa)的端到端变异效应预测流程,解决了缺乏作物特异性变异解读工具的问题,并可扩展至任意具有参考基因组和基因注释的作物物种。该方法整合基于深度学习的变异检测(DeepChem-Variant)与定制化植物基因组注释,使用RAP-DB基因模型及不依赖数据库的有害性评分,结合Grantham距离和BLOSUM62替换矩阵。通过在应激响应基因(OsDREB2a、OsDREB1F、SKC1)中进行靶向突变验证,正确分类了终止增益、错义和同义变异,并合理分配了高/中/低影响等级。对OsMT-3a的全面诱变研究在10天内分析了全部1,509个可能的单核苷酸变异,识别出353个高影响、447个中等影响和709个低影响变异——这一工作若采用传统湿实验方法需耗时2-4年。该计算框架使育种者能跨多种作物优先筛选变异用于实验验证,显著降低筛选成本,加快气候适应型作物品种的培育。
原文摘要 · Abstract (English)
Predicting functional consequences of genetic variants in crop genes remains a critical bottleneck for precision breeding programs. We present AgriVariant, an end-to-end pipeline for variant-effect prediction in rice (Oryza sativa) that addresses the lack of crop-specific variant-interpretation tools and can be extended to any crop species with available reference genomes and gene annotations. Our approach integrates deep learning-based variant calling (DeepChem-Variant) with custom plant genomics annotation using RAP-DB gene models and database-independent deleteriousness scoring that combines the Grantham distance and the BLOSUM62 substitution matrix. We validate the pipeline through targeted mutations in stress-response genes (OsDREB2a, OsDREB1F, SKC1), demonstrating correct classification of stop-gained, missense, and synonymous variants with appropriate HIGH / MODERATE / LOW impact assignments. An exhaustive mutagenesis study of OsMT-3a analyzed all 1,509 possible single-nucleotide variants in 10 days, identifying 353 high-impact, 447 medium-impact, and 709 low-impact variants - an analysis that would have required 2-4 years using traditional wet-lab approaches. This computational framework enables breeders to prioritize variants for experimental validation across diverse crop species, reducing screening costs and accelerating development of climate-resilient crop varieties.
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