Simultaneous discovery of cancer subtypes and subtype features by molecular data integration

Subtyping cancer is key to an improved and more personalized prognosis/treatment. The increasing availability of tumor related molecular data provides the opportunity to identify molecular subtypes in a data-driven way. Molecular subtypes are defined as groups of samples that have a similar molecular mechanism at the origin of the carcinogenesis. The molecular mechanisms are reflected by subtype-specific mutational and expression features. Data-driven subtyping is a complex problem as subtyping and identifying the molecular mechanisms that drive carcinogenesis are confounded problems. Many current integrative subtyping methods use global mutational and/or expression tumor profiles to group tumor samples in subtypes but do not explicitly extract the subtype-specific features. We therefore present a method that solves both tasks of subtyping and identification of subtype-specific features simultaneously. Hereto our method integrates` mutational and expression data while taking into account the clonal properties of carcinogenesis. Key to our method is a formalization of the problem as a rank matrix factorization of ranked data that approaches the subtyping problem as multi-view bi-clustering