用基因语言模型融合影像数据,提升神经疾病早期诊断准确率
Decoding Phenotypes: A Framework for Fusing Genomic Language Models and Neuroimaging

- 将基因语言模型嵌入影像特征,动态调节图像表示
- 在阿尔茨海默病和轻度认知障碍识别中分别达到0.77和0.83的AUROC
- 适合研究影像与基因融合、临床辅助诊断的学者使用
神经影像与基因检测是神经系统疾病的重要临床参考,提供互补的诊断信息。然而,由于跨模态异质性,整合基因组与影像数据实现精准诊断仍具挑战。现有方法多将遗传信息编码为固定标签,丢失致病位点周围的序列上下文信息。为此,我们提出GeneFuse,一种多模态学习框架,将预训练基因语言模型(GLMs)生成的基因表征与图像特征对齐。该框架包含两个组件:(1) 基因型条件特征调制(GCFM),受FiLM启发,利用基因嵌入调节图像特征图;(2) 不确定性感知基因残差融合(U-GRF),通过影像预测不确定性门控基因特征贡献。我们在早发认知衰退(NC vs. MCI)和痴呆筛查(NC vs. AD)任务上评估GeneFuse。在APOE相关设置下,其AUROC分别达0.77和0.83,优于现有影像-基因融合方法。结果表明,GLM提取的基因嵌入能为影像提供额外诊断信息。
原文摘要 · Abstract (English)
Neuroimaging and genetic testing are two important clinical references for nervous system diseases, offering complementary diagnostic information. However, integrating genomic and neuroimaging data for precise disease diagnosis is challenging due to cross-modality heterogeneity. Existing imaging-genetics approaches mainly encode genetic information as hard-coded labels, which lose the local sequence context around disease-associated variants. To address this limitation, we propose GeneFuse, a multimodal learning framework that aligns genetic representations from pre-trained Genomic Language Models (GLMs) with features extracted from images. GeneFuse integrates two components: (1) Genotype-Conditioned Feature Modulation (GCFM), a FiLM-inspired module that uses genomic embeddings to modulate image feature maps; and (2) Uncertainty-aware Genomic Residual Fusion (U-GRF), a fusion strategy that uses imaging-derived predictive uncertainty to gate the contribution of genotypic features. We evaluate GeneFuse on early cognitive decline identification (NC vs. MCI) and dementia screening (NC vs. AD). In the APOE-centered setting, GeneFuse achieves AUROCs of 0.77 and 0.83, outperforming existing imaging-genetics fusion methods. These results indicate that GLM-derived genomic embeddings provide additional information to imaging.
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