用Transformer提升肿瘤新抗原排序准确率,大幅减少训练时间。
TransNRank: Towards Accurate Neoantigen Ranking with Transformer
- 基于自注意力机制建模肽段全局上下文关系。
- 在三个数据集上将前20名召回率提升至53.1%(原46.9%),训练效率提高10倍。
- 发现突变锚点和TCGA表达水平对预测至关重要,可降维而不损性能。
个性化新抗原预测因正样本稀缺、实验数据噪声、严重类别不平衡及免疫原性特征复杂而面临挑战。现有方法如线性回归与XGBoost难以捕捉肽段特征中的长程依赖与上下文关系,导致新抗原正样本召回率受限。本文提出基于Transformer的深度学习框架TransNRank,利用自注意力机制同时建模局部与全局特征上下文,提升免疫原性新抗原识别精度。采用正样本感知训练目标缓解类别不平衡,赋予少数正样本更高权重。在NCI、TESLA和HiTIDE数据集上进行大量实验,结果表明:TransNRank将新抗原预测前20名召回率从46.9%(45/96)提升至53.1%(51/96),训练轮次由200次降至20次。进一步分析显示,突变锚点位置及TCGA表达水平在预测中起关键作用;去除无关特征降低输入维度后,模型性能未显著下降。该范式不仅简化预测流程,更刷新新抗原发现的最先进水平,对精准肿瘤免疫学具有重要意义。
原文摘要 · Abstract (English)
Personalized neoantigen prediction is challenging due to the scarcity of positive samples, the noise of the experimental data, the severe class imbalance trait and the complex of immunogenicity features. Prior arts, such as linear regression and XGBoost fail to model long-range dependencies and contextual relationships within peptide features, therefore the performance of neoantigen positive recall rate is limited. In this paper, we present a novel deep learning framework based on Transformer, coined as TransNRank. By leveraging the self-attention mechanism, our model captures both local and global feature contexts, enabling more accurate recognition of immunogenic neoantigens. A positive-aware training objective is utilized to handle the class imbalance problem, assigning more weights to those few positive samples. Extensive experiments are performed on NCI, TESLA and HiTIDE datasets. Notably, our TransNRank can push the upper bound top 20 recall rate of neoantigen prediction from 46.9% (45 from 96) to 53.1% (51 from 96), while reducing the training epochs from 200 epochs to 20 epochs. Furthermore, we analyze the features contribution based on TransNRank and find that the mutation at anchor and TCGA expression level play an unexpected important role in neoantigen prediction, and removing insignificant features to reduce the input dimensionality of peptides does not drastically impair the overall performance of the model. Our paradigm not only streamlines the prediction pipeline but also sets a new state-of-the-art for neoantigen discovery, with broad implications for accurate immuno-oncology.
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