GMAMDA:基于自适应硬度负采样和自适应图多重卷积预测代谢物-疾病关联

GMAMDA: Predicting Metabolite-Disease Associations Based on Adaptive Hardness Negative Sampling and Adaptive Graph Multiple Convolution.

作者信息

Hu Binglu, Su Ying, Tian Xuecong, Chen Chen, Chen Cheng, Lv Xiaoyi

机构信息

College of Software, Xinjiang University, Urumqi 830046, Xinjiang, China.

College of Information Science and Engineering, Xinjiang University, Urumqi 830046, China.

出版信息

J Chem Inf Model. 2025 May 26;65(10):5242-5254. doi: 10.1021/acs.jcim.5c00694. Epub 2025 May 15.

Abstract

Metabolites are small molecules produced during organism metabolism, with their abnormal concentrations closely linked to the onset and progression of various diseases. Accurate prediction of metabolite-disease associations is crucial for early diagnosis, mechanistic exploration, and treatment optimization. However, existing algorithms often overlook the integration of node features and neglect the impact of different hop domains on nodes in the processing of heterogeneous graphs. Furthermore, current methods solely rely on random sampling for selecting negative samples without considering their reliability, thereby compromising model stability. A novel metabolite-disease association prediction model, GMAMDA, is proposed to address these challenges. GMAMDA integrates adaptive hardness negative sampling, adaptive graph multiple convolution techniques, and a multiheterogeneous graph fusion strategy to forecast potential metabolite-disease associations. Initially, by computing multisource similarity information for metabolites and diseases, multiple heterogeneous graph networks are established for metabolite-disease association networks. Subsequently, the adaptive graph's multiconvolution mechanism is employed to generate feature-rich node representations across various heterogeneous graphs by dynamically leveraging information from different hop neighborhoods. The model then utilizes an adaptive hardness negative sampling approach based on principal component analysis to select negative samples with the highest information content for training, enabling the prediction of potential associations between new metabolites and diseases. Experimental findings demonstrate that GMAMDA outperforms state-of-the-art methods across various evaluation metrics, including AUC (0.9962 ± 0.0014), AUPR (0.9967 ± 0.0009), and accuracy (0.9733 ± 0.0042). Case studies focusing on Alzheimer's disease and kidney disease further validate GMAMDA's clinical potential in predicting metabolite markers.

摘要

代谢物是生物体新陈代谢过程中产生的小分子,其浓度异常与各种疾病的发生和发展密切相关。准确预测代谢物与疾病的关联对于早期诊断、机制探索和治疗优化至关重要。然而,现有算法往往忽视节点特征的整合,在处理异构图时忽略不同跳域对节点的影响。此外,当前方法仅依靠随机采样来选择负样本,而不考虑其可靠性,从而影响模型稳定性。为应对这些挑战,提出了一种新型代谢物-疾病关联预测模型GMAMDA。GMAMDA集成了自适应硬度负采样、自适应图多重卷积技术和多异构图融合策略,以预测潜在的代谢物-疾病关联。首先,通过计算代谢物和疾病的多源相似性信息,为代谢物-疾病关联网络建立多个异构图网络。随后,采用自适应图的多卷积机制,通过动态利用来自不同跳邻域的信息,在各种异构图上生成特征丰富的节点表示。该模型然后利用基于主成分分析的自适应硬度负采样方法选择信息含量最高的负样本进行训练,从而能够预测新代谢物与疾病之间的潜在关联。实验结果表明,GMAMDA在包括AUC(0.9962±0.0014)、AUPR(0.9967±0.0009)和准确率(0.9733±0.0042)等各种评估指标上均优于现有方法。针对阿尔茨海默病和肾病的案例研究进一步验证了GMAMDA在预测代谢物标志物方面的临床潜力。

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