Towards multi-omics characterization of tumor heterogeneity: a comprehensive review of statistical and machine learning approaches.

The multi-omics molecular characterization of cancer opened a new horizon for our understanding of cancer biology and therapeutic strategies. However, a tumor biopsy comprises diverse types of cells limited not only to cancerous cells but also to tumor microenvironmental cells and adjacent normal cells. This heterogeneity is a major confounding factor that hampers a robust and reproducible bioinformatic analysis for biomarker identification using multi-omics profiles. Besides, the heterogeneity itself has been recognized over the years for its significant prognostic values in some cancer types, thus offering another promising avenue for therapeutic intervention. A number of computational approaches to unravel such heterogeneity from high-throughput molecular profiles of a tumor sample have been proposed, but most of them rely on the data from an individual omics layer. Since the heterogeneity of cells is widely distributed across multi-omics layers, methods based on an individual layer can only partially characterize the heterogeneous admixture of cells. To help facilitate further development of the methodologies that synchronously account for several multi-omics profiles, we wrote a comprehensive review of diverse approaches to characterize tumor heterogeneity based on three different omics layers: genome, epigenome and transcriptome. As a result, this review can be useful for the analysis of multi-omics profiles produced by many large-scale consortia. Contact:sunkim.bioinfo@snu.ac.kr.