Multi-Omics Data Fusion via a Joint Kernel Learning Model for Cancer Subtype Discovery and Essential Gene Identification

Abstract

The multiple sources of cancer determine its multiple causes, and the same cancer can be composed of many different subtypes. Identification of cancer subtypes is a key part of personalized cancer treatment and provides an important reference for clinical diagnosis and treatment. Some studies have shown that there are significant differences in the genetic and epigenetic profiles among different cancer subtypes during carcinogenesis and development. In this study, we first collect seven cancer datasets from the Broad Institute GDAC Firehose, including gene expression profile, isoform expression profile, DNA methylation expression data, and survival information correspondingly. Furthermore, we employ kernel principal component analysis (PCA) to extract features for each expression profile, convert them into three similarity kernel matrices by Gaussian kernel function, and then fuse these matrices as a global kernel matrix. Finally, we apply it to spectral clustering algorithm to get the clustering results of different cancer subtypes. In the experimental results, besides using the P-value from the Cox regression model and survival analysis as the primary evaluation measures, we also introduce statistical indicators such as Rand index (RI) and adjusted RI (ARI) to verify the performance of clustering. Then combining with gene expression profile, we obtain the differential expression of genes among different subtypes by gene set enrichment analysis. For lung cancer, GMPS, EPHA10, C10orf54, and MAGEA6 are highly expressed in different subtypes; for liver cancer, CMYA5, DEPDC6, FAU, VPS24, RCBTB2, LOC100133469, and SLC35B4 are significantly expressed in different subtypes.

Keywords: GSEA; cancer subtype; kernel PCA; spectral clustering; survival analysis.