Abstract

The identification of cancer subtypes is important for the understanding of tumor heterogeneity. In recent years, numerous computational methods have been proposed for this problem based on the multi-omics data of patients. It is widely accepted that different cancer subtypes are induced by different molecular regulatory networks. However, only a few incorporate the differences between their molecular systems into the identification processes. In this study, we present a novel method to identify cancer subtypes based on patient-specific molecular systems. Our method realizes this by quantifying patient-specific gene networks, which are estimated from their transcriptome data, and by clustering their quantified networks. Comprehensive analyses of The Cancer Genome Atlas (TCGA) datasets applied to our method confirmed that they were able to identify more clinically meaningful cancer subtypes than the existing subtypes and found that the identified subtypes comprised different molecular features. Our findings also show that the proposed method can identify the novel cancer subtypes even with single omics data, which cannot otherwise be captured by existing methods using multi-omics data.

Highlights

  • The identification of cancer subtypes is important for the understanding of tumor heterogeneity

  • lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were regarded as one dataset and referred to lung cancer dataset (LUNG) as they are both lung cancers, and we test whether they are split into different subtypes

  • To select the edges for hierarchical clustering based on the edge contribution value (ECv) matrix, the variances of edges were calculated as described in Method section

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Summary

Introduction

The identification of cancer subtypes is important for the understanding of tumor heterogeneity. We present a novel method to identify cancer subtypes based on patient-specific molecular systems. The Cancer Genome Atlas (TCGA) contains multi-omics data, including gene expression, mutation, methylation, and copy number, of over 34 cancer types. This idea can be applied to obtain an understanding of complex human diseases, and is known as network medicine where the diseases are rarely caused by single molecular defects but are more likely driven by combinations of various biological p­ rocesses[4,5,6,7,8,9,10,11] This concept has already been employed in recent cutting-edge research for discovering cancer-related ­genes[12,13,14]. Because genetic interactions are condition-specific, the networks of particular types of cancers are different from those found in these databases

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