用主动学习高效找到最优基因组合,加速抗癌疗法研发
Active learning for efficient discovery of optimal gene combinations in the combinatorial perturbation space
- 基于单基因效应和自适应基因嵌入,动态学习复杂基因互作
- 小样本训练下性能比现有模型高40%,在35万+基因互作数据上验证
- 每轮推荐最大潜力基因对,减少实验次数,适合药物研发与基因组研究
新型组合CRISPR筛选技术可大规模识别协同作用的基因组合,对开发新疗法至关重要,但组合空间过大导致全量实验不可行。我们提出NAIAD主动学习框架,能高效发现驱动细胞向目标表型转变的最优基因对。该框架利用单基因扰动效应与随训练数据规模自适应的基因嵌入,小样本下避免过拟合,数据增多时捕捉复杂基因互作。在包含超过35万条遗传互作的四个CRISPR组合扰动数据集上评估,NAIAD在小样本训练下性能比第二优模型高出最多40%。其推荐系统优先选择预测效应最大的基因对,每轮实验带来最高边际增益,显著减少所需CRISPR实验迭代次数。NAIAD框架(https://github.com/NeptuneBio/NAIAD)提升了新有效基因组合的发现效率,助力更优CRISPR文库设计,在基因组研究与治疗开发中具广泛应用前景。
原文摘要 · Abstract (English)
The advancement of novel combinatorial CRISPR screening technologies enables the identification of synergistic gene combinations on a large scale. This is crucial for developing novel and effective combination therapies, but the combinatorial space makes exhaustive experimentation infeasible. We introduce NAIAD, an active learning framework that efficiently discovers optimal gene pairs capable of driving cells toward desired cellular phenotypes. NAIAD leverages single-gene perturbation effects and adaptive gene embeddings that scale with the training data size, mitigating overfitting in small-sample learning while capturing complex gene interactions as more data is collected. Evaluated on four CRISPR combinatorial perturbation datasets totaling over 350,000 genetic interactions, NAIAD, trained on small datasets, outperforms existing models by up to 40\% relative to the second-best. NAIAD's recommendation system prioritizes gene pairs with the maximum predicted effects, resulting in the highest marginal gain in each AI-experiment round and accelerating discovery with fewer CRISPR experimental iterations. Our NAIAD framework (https://github.com/NeptuneBio/NAIAD) improves the identification of novel, effective gene combinations, enabling more efficient CRISPR library design and offering promising applications in genomics research and therapeutic development.
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