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StellarPath:分层垂直多组学分类器结合稳定标志物和可解释的相似性网络进行患者特征分析。

StellarPath: Hierarchical-vertical multi-omics classifier synergizes stable markers and interpretable similarity networks for patient profiling.

作者信息

Giudice Luca, Mohamed Ahmed, Malm Tarja

机构信息

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

出版信息

PLoS Comput Biol. 2024 Apr 12;20(4):e1012022. doi: 10.1371/journal.pcbi.1012022. eCollection 2024 Apr.

Abstract

The Patient Similarity Network paradigm implies modeling the similarity between patients based on specific data. The similarity can summarize patients' relationships from high-dimensional data, such as biological omics. The end PSN can undergo un/supervised learning tasks while being strongly interpretable, tailored for precision medicine, and ready to be analyzed with graph-theory methods. However, these benefits are not guaranteed and depend on the granularity of the summarized data, the clarity of the similarity measure, the complexity of the network's topology, and the implemented methods for analysis. To date, no patient classifier fully leverages the paradigm's inherent benefits. PSNs remain complex, unexploited, and meaningless. We present StellarPath, a hierarchical-vertical patient classifier that leverages pathway analysis and patient similarity concepts to find meaningful features for both classes and individuals. StellarPath processes omics data, hierarchically integrates them into pathways, and uses a novel similarity to measure how patients' pathway activity is alike. It selects biologically relevant molecules, pathways, and networks, considering molecule stability and topology. A graph convolutional neural network then predicts unknown patients based on known cases. StellarPath excels in classification performances and computational resources across sixteen datasets. It demonstrates proficiency in inferring the class of new patients described in external independent studies, following its initial training and testing phases on a local dataset. It advances the PSN paradigm and provides new markers, insights, and tools for in-depth patient profiling.

摘要

患者相似性网络范式意味着基于特定数据对患者之间的相似性进行建模。这种相似性可以从高维数据(如生物组学数据)中总结出患者之间的关系。最终的患者相似性网络可以进行无监督/有监督学习任务,同时具有很强的可解释性,专为精准医学量身定制,并可通过图论方法进行分析。然而,这些优势并非必然,而是取决于汇总数据的粒度、相似性度量的清晰度、网络拓扑结构的复杂性以及所实施的分析方法。迄今为止,尚无患者分类器能充分利用该范式的内在优势。患者相似性网络仍然复杂、未被充分利用且毫无意义。我们提出了StellarPath,这是一种分层垂直患者分类器,它利用通路分析和患者相似性概念为类别和个体找到有意义的特征。StellarPath处理组学数据,将它们分层整合到通路中,并使用一种新颖的相似性来衡量患者的通路活性有多相似。它会考虑分子稳定性和拓扑结构,选择具有生物学相关性的分子、通路和网络。然后,图卷积神经网络根据已知病例预测未知患者。在十六个数据集上,StellarPath在分类性能和计算资源方面表现出色。在对本地数据集进行初始训练和测试阶段之后,它在推断外部独立研究中描述的新患者类别方面表现出了专业能力。它推动了患者相似性网络范式的发展,并为深入的患者剖析提供了新的标志物、见解和工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/207e/11042724/c17dfab001c8/pcbi.1012022.g001.jpg

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