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

机译:来自超脑黑素瘤的多域基因组数据集成的数据融合技术

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摘要

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.
机译:UVEAL黑色素瘤(UM)是一种罕见的癌症,其在分子水平上很好地表征。通过分析基因表达(mRNA,NCRNA),DNA拷贝数,DNA-甲基化和体细胞突变,鉴定了两到四种类别,但没有报告这些数据的事实整合。因此,我们应用了用于数据融合的新算法,关节奇异值分解(JSVD)和联合受限矩阵分解(JCMF),以及相似性网络融合(SNF),用于我们应用的基因表达,甲基化和拷贝数数据的整合到癌症基因组图集(TCGA)UM数据集。提取了对类别定义的变体特征是针对类别的生物解释。数据融合允许识别先前描述的两到四个类。并非所有这些课程都在所有级别都很明显,这表明综合分析增加了基因组辨别力。该类的特征还表征在推定驾驶员基因(GNAQ,GNA11,SF3B1,BAP1)中的细胞突变频率不同。根据预期,创新的数据融合技术确认了两种主要类型的无过性黑色素瘤,主要是拷贝数改变。亚型也得到证实,但定义了一些。数据融合允许实际集成多域基因组数据。

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