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HCNM:用于癌症亚型预测的多组学数据多层次综合研究的异质相关网络模型。

HCNM: Heterogeneous Correlation Network Model for Multi-level Integrative Study of Multi-omics Data for Cancer Subtype Prediction.

出版信息

Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:1880-1886. doi: 10.1109/EMBC46164.2021.9630781.

Abstract

Integrative analysis of multi-omics data is important for biomedical applications, as it is required for a comprehensive understanding of biological function. Integrating multi-omics data serves multiple purposes, such as, an integrated data model, dimensionality reduction of omic features, patient clustering, etc. For oncological data, patient clustering is synonymous to cancer subtype prediction. However, there is a gap in combining some of the widely used integrative analyses to build more powerful tools. To bridge the gap, we propose a multi-level integration algorithm to identify representative integrative subspace and use it for cancer subtype prediction. The three integrative approaches we implement on multi-omics features are, (1) multivariate multiple (linear) regression of the features from a cohort of patients/samples, (2) network construction using different omics features, and (3) fusion of sample similarity networks across the features. We use a type of multilayer network, called heterogeneous network, as a data model to transition between a network-free (NF) regression model and a network-based (NB) model, which uses correlation networks. The heterogeneous networks consist of intra- and inter-layer graphs. Our proposed heterogeneous correlation network model, HCNM, is central to our algorithm for gene-ranking, integrative subspace identification, and tumor-specific subtypes prediction. The genes of our representative integrative subspace have been enriched with gene-ontology and found to exhibit significant gene-disease association (GDA) scores. The subspace in genes which is less than 5% of the total gene-set of each genomic feature is used with NB fusion integrative model to predict sample subtypes. As the identified integrative subspace data of multi-omics is less prone to noise, bias, and outliers, our experiments show that the subtypes in our results agree with previous benchmark studies and exhibit better classification between poor and good survival of patient cohorts.Clinical relevance: Finding significant cancer-specific genes and subtypes of cancer is vital for early prognosis, and personalized treatment; therefore, improves survival probability of a patient.

摘要

多组学数据的综合分析对于生物医学应用非常重要,因为它是全面理解生物功能所必需的。整合多组学数据有多种用途,例如,建立综合数据模型、降低组学特征的维度、对患者进行聚类等。对于肿瘤学数据,患者聚类等同于癌症亚型预测。然而,在整合一些广泛使用的综合分析方法来构建更强大的工具方面存在差距。为了弥合这一差距,我们提出了一种多层次的整合算法,以识别有代表性的整合子空间,并将其用于癌症亚型预测。我们在多组学特征上实施了三种整合方法,分别是:(1)对患者/样本队列中的特征进行多元多(线性)回归,(2)使用不同的组学特征构建网络,以及(3)融合跨特征的样本相似性网络。我们使用一种称为异质网络的多层网络作为数据模型,在无网络(NF)回归模型和基于网络(NB)模型之间进行转换,后者使用相关网络。异质网络由内层图和层间图组成。我们提出的异质相关网络模型 HCNM 是我们用于基因排序、整合子空间识别和肿瘤特异性亚型预测的算法的核心。我们代表性整合子空间的基因通过基因本体论富集,并发现其具有显著的基因疾病关联(GDA)评分。使用 NB 融合整合模型来预测样本亚型的基因少于每个基因组特征总基因集的 5%。由于多组学的代表性整合子空间数据不易受到噪声、偏差和异常值的影响,我们的实验表明,我们的结果中的亚型与之前的基准研究一致,并在患者队列的不良和良好生存之间表现出更好的分类。临床意义:发现显著的癌症特异性基因和癌症亚型对于早期预后和个性化治疗至关重要,因此可以提高患者的生存概率。

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