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使用图神经网络结合神经影像和组学数据集进行疾病分类

Combining Neuroimaging and Omics Datasets for Disease Classification Using Graph Neural Networks.

作者信息

Chan Yi Hao, Wang Conghao, Soh Wei Kwek, Rajapakse Jagath C

机构信息

School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore.

出版信息

Front Neurosci. 2022 May 23;16:866666. doi: 10.3389/fnins.2022.866666. eCollection 2022.

Abstract

Both neuroimaging and genomics datasets are often gathered for the detection of neurodegenerative diseases. Huge dimensionalities of neuroimaging data as well as omics data pose tremendous challenge for methods integrating multiple modalities. There are few existing solutions that can combine both multi-modal imaging and multi-omics datasets to derive neurological insights. We propose a deep neural network architecture that combines both structural and functional connectome data with multi-omics data for disease classification. A graph convolution layer is used to model functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data simultaneously to learn compact representations of the connectome. A separate set of graph convolution layers are then used to model multi-omics datasets, expressed in the form of population graphs, and combine them with latent representations of the connectome. An attention mechanism is used to fuse these outputs and provide insights on which omics data contributed most to the model's classification decision. We demonstrate our methods for Parkinson's disease (PD) classification by using datasets from the Parkinson's Progression Markers Initiative (PPMI). PD has been shown to be associated with changes in the human connectome and it is also known to be influenced by genetic factors. We combine DTI and fMRI data with multi-omics data from RNA Expression, Single Nucleotide Polymorphism (SNP), DNA Methylation and non-coding RNA experiments. A Matthew Correlation Coefficient of greater than 0.8 over many combinations of multi-modal imaging data and multi-omics data was achieved with our proposed architecture. To address the paucity of paired multi-modal imaging data and the problem of imbalanced data in the PPMI dataset, we compared the use of oversampling against using CycleGAN on structural and functional connectomes to generate missing imaging modalities. Furthermore, we performed ablation studies that offer insights into the importance of each imaging and omics modality for the prediction of PD. Analysis of the generated attention matrices revealed that DNA Methylation and SNP data were the most important omics modalities out of all the omics datasets considered. Our work motivates further research into imaging genetics and the creation of more multi-modal imaging and multi-omics datasets to study PD and other complex neurodegenerative diseases.

摘要

神经影像学和基因组学数据集通常都是为了检测神经退行性疾病而收集的。神经影像学数据以及组学数据的巨大维度给整合多种模态的方法带来了巨大挑战。现有的能够结合多模态成像和多组学数据集以获得神经学见解的解决方案很少。我们提出了一种深度神经网络架构,该架构将结构和功能连接组数据与多组学数据相结合用于疾病分类。一个图卷积层用于同时对功能磁共振成像(fMRI)和扩散张量成像(DTI)数据进行建模,以学习连接组的紧凑表示。然后使用单独的一组图卷积层对以群体图形式表示的多组学数据集进行建模,并将它们与连接组的潜在表示相结合。一种注意力机制用于融合这些输出,并提供关于哪些组学数据对模型的分类决策贡献最大的见解。我们通过使用来自帕金森病进展标记倡议(PPMI)的数据集来展示我们用于帕金森病(PD)分类的方法。PD已被证明与人类连接组的变化有关,并且已知受遗传因素影响。我们将DTI和fMRI数据与来自RNA表达、单核苷酸多态性(SNP)、DNA甲基化和非编码RNA实验的多组学数据相结合。我们提出的架构在多模态成像数据和多组学数据的许多组合上实现了大于0.8的马修相关系数。为了解决PPMI数据集中配对多模态成像数据的稀缺以及数据不平衡问题,我们比较了过采样与在结构和功能连接组上使用CycleGAN来生成缺失成像模态的效果。此外,我们进行了消融研究,以深入了解每种成像和组学模态对PD预测的重要性。对生成的注意力矩阵的分析表明,在所有考虑的组学数据集中,DNA甲基化和SNP数据是最重要的组学模态。我们的工作推动了对影像遗传学的进一步研究,以及创建更多的多模态成像和多组学数据集来研究PD和其他复杂的神经退行性疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf3e/9168232/88cc95d6b3f0/fnins-16-866666-g0001.jpg

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