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

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.

Towards multiple kernel principal component analysis for integrative analysis of tumor samples

Personalized treatment of patients based on tissue-specific cancer subtypes has strongly increased the efficacy of the chosen therapies. Even though the amount of data measured for cancer patients has increased over the last years, most cancer subtypes are still diagnosed based on individual data sources (e.g. gene expression data). We propose an unsupervised data integration method based on kernel principal component analysis. Principal component analysis is one of the most widely used techniques in data analysis. Unfortunately, the straight-forward multiple-kernel extension of this method leads to the use of only one of the input matrices, which does not fit the goal of gaining information from all data sources. Therefore, we present a scoring function to determine the impact of each input matrix. The approach enables visualizing the integrated data and subsequent clustering for cancer subtype identification. Due to the nature of the method, no free parameters have to be set. We apply the methodology to five different cancer data sets and demonstrate its advantages in terms of results and usability.