论文标题

基于对比度学习的计算组织病理学预测癌症驱动基因的差异表达

Contrastive learning-based computational histopathology predict differential expression of cancer driver genes

论文作者

Huang, Haojie, Zhou, Gongming, Liu, Xuejun, Deng, Lei, Wu, Chen, Zhang, Dachuan, Liu, Hui

论文摘要

数字病理分析作为用于癌症诊断的主要检查。最近,从病理图像中进行深度学习驱动的特征提取能够检测遗传变异和肿瘤环境,但是很少有研究集中于肿瘤细胞中的差异基因表达。在本文中,我们提出了一个自我监管的对比学习框架HistCode,以从整个幻灯片图像(WSIS)中推断出差异基因表达式。我们利用对大规模未注明的WSI的对比度学习,以在潜在空间中得出幻灯片水平的组织病理学特征,然后将其转移到肿瘤诊断和预测差异表达的癌症驱动基因基因。我们的广泛实验表明,我们的方法在肿瘤诊断任务中的表现优于其他最先进的模型,并且还有效地预测了差异基因表达。有趣的是,我们发现可以更精确地预测较高的倍数变化基因。为了直观地说明从病理性图像中提取信息特征的能力,我们通过图像瓷砖的细心分数从空间可视化了WSIS。我们发现肿瘤和坏死区与经验丰富的病理学家的注释高度一致。此外,由淋巴细胞特异性基因表达模式产生的空间热图也与手动标记的WSI一致。

Digital pathological analysis is run as the main examination used for cancer diagnosis. Recently, deep learning-driven feature extraction from pathology images is able to detect genetic variations and tumor environment, but few studies focus on differential gene expression in tumor cells. In this paper, we propose a self-supervised contrastive learning framework, HistCode, to infer differential gene expressions from whole slide images (WSIs). We leveraged contrastive learning on large-scale unannotated WSIs to derive slide-level histopathological feature in latent space, and then transfer it to tumor diagnosis and prediction of differentially expressed cancer driver genes. Our extensive experiments showed that our method outperformed other state-of-the-art models in tumor diagnosis tasks, and also effectively predicted differential gene expressions. Interestingly, we found the higher fold-changed genes can be more precisely predicted. To intuitively illustrate the ability to extract informative features from pathological images, we spatially visualized the WSIs colored by the attentive scores of image tiles. We found that the tumor and necrosis areas were highly consistent with the annotations of experienced pathologists. Moreover, the spatial heatmap generated by lymphocyte-specific gene expression patterns was also consistent with the manually labeled WSI.

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