Effective integration of multi-omics with prior knowledge to identify biomarkers via explainable graph neural networks.

IF 3.5 2区 生物学 Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY
Rohit K Tripathy, Zachary Frohock, Hong Wang, Gregory A Cary, Stephen Keegan, Gregory W Carter, Yi Li
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引用次数: 0

Abstract

The rapid growth of multi-omics datasets and the wealth of biological knowledge necessitates the development of effective methods for their integration. Such methods are essential for building predictive models and identifying drug targets based on a limited number of samples. We propose a framework called GNNRAI for the supervised integration of multi-omics data with biological priors represented as knowledge graphs. Our framework leverages graph neural networks (GNNs) to model the correlation structures among features from high-dimensional 'omics data, which reduces the effective dimensions in data and enables us to analyze thousands of genes simultaneously using hundreds of samples. Furthermore, our framework incorporates explainability methods to elucidate informative biomarkers. We apply our framework to Alzheimer's disease (AD) multi-omics data, showing that the integration of transcriptomics and proteomics data with prior AD knowledge is effective, improving the prediction accuracy of AD status over single-omics analyses and highlighting both known and novel AD-predictive biomarkers.

多组学与先验知识的有效整合,通过可解释的图神经网络识别生物标志物。
多组学数据集的快速增长和丰富的生物学知识需要开发有效的方法来整合它们。这些方法对于基于有限数量的样本建立预测模型和确定药物靶点至关重要。我们提出了一个名为GNNRAI的框架,用于多组学数据与以知识图表示的生物先验的监督集成。我们的框架利用图神经网络(gnn)来模拟高维组学数据中特征之间的相关结构,这减少了数据中的有效维数,使我们能够同时使用数百个样本分析数千个基因。此外,我们的框架结合了可解释性方法来阐明信息性生物标志物。我们将我们的框架应用于阿尔茨海默病(AD)的多组学数据,表明转录组学和蛋白质组学数据与先前的AD知识的整合是有效的,提高了单组学分析对AD状态的预测准确性,并突出了已知和新的AD预测生物标志物。
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来源期刊
NPJ Systems Biology and Applications
NPJ Systems Biology and Applications Mathematics-Applied Mathematics
CiteScore
5.80
自引率
0.00%
发文量
46
审稿时长
8 weeks
期刊介绍: npj Systems Biology and Applications is an online Open Access journal dedicated to publishing the premier research that takes a systems-oriented approach. The journal aims to provide a forum for the presentation of articles that help define this nascent field, as well as those that apply the advances to wider fields. We encourage studies that integrate, or aid the integration of, data, analyses and insight from molecules to organisms and broader systems. Important areas of interest include not only fundamental biological systems and drug discovery, but also applications to health, medical practice and implementation, big data, biotechnology, food science, human behaviour, broader biological systems and industrial applications of systems biology. We encourage all approaches, including network biology, application of control theory to biological systems, computational modelling and analysis, comprehensive and/or high-content measurements, theoretical, analytical and computational studies of system-level properties of biological systems and computational/software/data platforms enabling such studies.
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