An interpretable multiple kernel learning approach for the discovery of integrative cancer subtypes

Nora K. Speicher, Nico Pfeifer

Due to the complexity of cancer, clustering algorithms have been used to disentangle the observed heterogeneity and identify cancer subtypes that can be treated specifically. While kernel based clustering approaches allow the use of more than one input matrix, which is an important factor when considering a multidimensional disease like cancer, the clustering results remain hard to evaluate and, in many cases, it is unclear which piece of information had which impact on the final result. In this paper, we propose an extension of multiple kernel learning clustering that enables the characterization of each identified patient cluster based on the features that had the highest impact on the result. To this end, we combine feature clustering with multiple kernel dimensionality reduction and introduce FIPPA, a score which measures the feature cluster impact on a patient cluster. Results: We applied the approach to different cancer types described by four different data types with the aim of identifying integrative patient subtypes and understanding which features were most important for their identification. Our results show that our method does not only have state-of-the-art performance according to standard measures (e.g., survival analysis), but, based on the high impact features, it also produces meaningful explanations for the molecular bases of the subtypes. This could provide an important step in the validation of potential cancer subtypes and enable the formulation of new hypotheses concerning individual patient groups. Similar analysis are possible for other disease phenotypes.

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