Path-GPTOmic:用于生存结果预测的平衡多模态学习框架

Hongxiao Wang, Yang Yang, Zhuo Zhao, Pengfei Gu, Nishchal Sapkota, Danny Z. Chen
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引用次数: 0

摘要

为预测癌症生存结果,临床研究中的标准方法通常基于两种主要模式:用于观察细胞形态特征的病理图像和用于量化基因表达的基因组学(如批量 RNA-seq)。然而,现有的病理-基因组多模态算法面临着重大挑战:(1)关于基因和基因-基因相互作用的宝贵生物学见解经常被忽视;(2)一种模态经常主导优化过程,导致另一种模态的训练不足。在本文中,我们为癌症生存结果预测引入了一种新的多模态 "Path-GPTOmic "框架。首先,为了提取有价值的生物学见解,我们调节了基础模型 scGPT 的嵌入空间,该模型最初是在单细胞 RNA-seq 数据上训练的,使其能够适应大量 RNA-seq 数据。其次,为了解决模态间的不平衡问题,我们提出了一种梯度调节机制,该机制是为生存预测的 Cox 部分似然损失量身定制的。在训练过程中,我们会动态监测和调整两种模态的贡献,以确保两种模态都得到充分训练。在两个TCGA(The CancerGenome Atlas)数据集上进行评估后,我们的模型大大提高了生存预测的准确性。
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Path-GPTOmic: A Balanced Multi-modal Learning Framework for Survival Outcome Prediction
For predicting cancer survival outcomes, standard approaches in clinical research are often based on two main modalities: pathology images for observing cell morphology features, and genomic (e.g., bulk RNA-seq) for quantifying gene expressions. However, existing pathology-genomic multi-modal algorithms face significant challenges: (1) Valuable biological insights regarding genes and gene-gene interactions are frequently overlooked; (2) one modality often dominates the optimization process, causing inadequate training for the other modality. In this paper, we introduce a new multi-modal ``Path-GPTOmic" framework for cancer survival outcome prediction. First, to extract valuable biological insights, we regulate the embedding space of a foundation model, scGPT, initially trained on single-cell RNA-seq data, making it adaptable for bulk RNA-seq data. Second, to address the imbalance-between-modalities problem, we propose a gradient modulation mechanism tailored to the Cox partial likelihood loss for survival prediction. The contributions of the modalities are dynamically monitored and adjusted during the training process, encouraging that both modalities are sufficiently trained. Evaluated on two TCGA(The Cancer Genome Atlas) datasets, our model achieves substantially improved survival prediction accuracy.
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