Data Fusion Techniques for the Integration of Multi-Domain Genomic Data from Uveal Melanoma.

Max Pfeffer,André Uschmajew,Ulrich Pfeffer,Adriana Amaro

doi:10.3390/cancers11101434

Abstract

Uveal melanoma (UM) is a rare cancer that is well characterized at the molecular level. Two to four classes have been identified by the analyses of gene expression (mRNA, ncRNA), DNA copy number, DNA-methylation and somatic mutations yet no factual integration of these data has been reported. We therefore applied novel algorithms for data fusion, joint Singular Value Decomposition (jSVD) and joint Constrained Matrix Factorization (jCMF), as well as similarity network fusion (SNF), for the integration of gene expression, methylation and copy number data that we applied to the Cancer Genome Atlas (TCGA) UM dataset. Variant features that most strongly impact on definition of classes were extracted for biological interpretation of the classes. Data fusion allows for the identification of the two to four classes previously described. Not all of these classes are evident at all levels indicating that integrative analyses add to genomic discrimination power. The classes are also characterized by different frequencies of somatic mutations in putative driver genes (GNAQ, GNA11, SF3B1, BAP1). Innovative data fusion techniques confirm, as expected, the existence of two main types of uveal melanoma mainly characterized by copy number alterations. Subtypes were also confirmed but are somewhat less defined. Data fusion allows for real integration of multi-domain genomic data.

Highlights

Uveal melanoma (UM) accounts for approximately 5% of all melanomas [1]
The the Cancer Genome Atlas (TCGA)-UVM dataset consists of several datasets: gene expression, DNA-methylation, DNA copy number alterations (CNA) and somatic mutation data
In the scope of this article, we constrain ourselves to the three datasets of mRNA expression data, DNA-methylation data, and CNA data, which we will store in three matrices

Summary

Introduction

Uveal melanoma (UM) accounts for approximately 5% of all melanomas [1]. Therapy, enucleation, endoresection or radiotherapy, almost completely controls primary tumors but 25% and 34% of UM patients develop metastases within 5 and 10 years, respectively. Median survival after diagnosis of metastatic UM is approximately one year [3]. The long-term cumulative melanoma-related mortality rate is over 50%. For medium and large tumors at 25 years after primary treatment [4]. UM is clearly distinct from cutaneous melanoma by different driver mutations, different chromosomal copy number alterations, a much lower mutational burden, and has to be treated as a different disease despite the common developmental origin of uveal and cutaneous melanocytes [5,6]

Objectives

Methods

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Discussion

Conclusion