title: Integrating different data types by regularized unsupervised multiple kernel learning with application to cancer subtype discovery.
abstract: BACKGROUND
  Despite ongoing cancer research, available therapies are still limited in quantity and effectiveness, and making treatment decisions for individual patients remains a hard problem. Established subtypes, which help guide these decisions, are mainly based on individual data types. However, the analysis of multidimensional patient data involving the measurements of various molecular features could reveal intrinsic characteristics of the tumor. Large-scale projects accumulate this kind of data for various cancer types, but we still lack the computational methods to reliably integrate this information in a meaningful manner. Therefore, we apply and extend current multiple kernel learning for dimensionality reduction approaches. On the one hand, we add a regularization term to avoid overfitting during the optimization procedure, and on the other hand, we show that one can even use several kernels per data type and thereby alleviate the user from having to choose the best kernel functions and kernel parameters for each data type beforehand.
  
  
  RESULTS
  We have identified biologically meaningful subgroups for five different cancer types. Survival analysis has revealed significant differences between the survival times of the identified subtypes, with P values comparable or even better than state-of-the-art methods. Moreover, our resulting subtypes reflect combined patterns from the different data sources, and we demonstrate that input kernel matrices with only little information have less impact on the integrated kernel matrix. Our subtypes show different responses to specific therapies, which could eventually assist in treatment decision making.
  
  
  METHODS
  An executable is available upon request.
authors.affiliation: Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbrücken and Saarbrücken Graduate School of Computer Science, Saarland University, 66123 Saarbrücken Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbrücken and Saarbrücken Graduate School of Computer Science, Saarland University, 66123 Saarbrücken.
authors.forename: Nora K
authors.initials: NK
authors.lastname: Speicher
authors.affiliation: Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbrücken and Saarbrücken Graduate School of Computer Science, Saarland University, 66123 Saarbrücken.
authors.forename: Nico
authors.initials: N
authors.lastname: Pfeifer
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D006801:Humans; D000069550:Machine Learning; D009369:Neoplasms / Q000145:classification* / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis