Gene Expression based Survival Prediction for Cancer Patients: A Topic Modeling Approach

Cancer is one of the leading cause of death, worldwide. Many believe that genomic data will enable us to better predict the survival time of these patients, which will lead to better, more personalized treatment options and patient care. As standard survival prediction models have a hard time coping with the high-dimensionality of such gene expression (GE) data, many projects use some dimensionality reduction techniques to overcome this hurdle. We introduce a novel methodology, inspired by topic modeling from the natural language domain, to derive expressive features from the high-dimensional GE data. There, a document is represented as a mixture over a relatively small number of topics, where each topic corresponds to a distribution over the words; here, to accommodate the heterogeneity of a patient's cancer, we represent each patient (~document) as a mixture over cancer-topics, where each cancer-topic is a mixture over GE values (~words). This required some extensions to the standard LDA model eg: to accommodate the "real-valued" expression values - leading to our novel "discretized" Latent Dirichlet Allocation (dLDA) procedure. We initially focus on the METABRIC dataset, which describes breast cancer patients using the r=49,576 GE values, from microarrays. Our results show that our approach provides survival estimates that are more accurate than standard models, in terms of the standard Concordance measure. We then validate this approach by running it on the Pan-kidney (KIPAN) dataset, over r=15,529 GE values - here using the mRNAseq modality - and find that it again achieves excellent results. In both cases, we also show that the resulting model is calibrated, using the recent "D-calibrated" measure. These successes, in two different cancer types and expression modalities, demonstrates the generality, and the effectiveness, of this approach

Nonconvex notions of regularity and convergence of fundamental algorithms for feasibility problems

We consider projection algorithms for solving (nonconvex) feasibility problems in Euclidean spaces. Of special interest are the Method of Alternating Projections (MAP) and the Douglas-Rachford or Averaged Alternating Reflection Algorithm (AAR). In the case of convex feasibility, firm nonexpansiveness of projection mappings is a global property that yields global convergence of MAP and for consistent problems AAR. Based on (\epsilon, \delta)-regularity of sets developed by Bauschke, Luke, Phan and Wang in 2012, a relaxed local version of firm nonexpansiveness with respect to the intersection is introduced for consistent feasibility problems. Together with a coercivity condition that relates to the regularity of the intersection, this yields local linear convergence of MAP for a wide class of nonconvex problems,Comment: 22 pages, no figures, 30 reference

Alternating Projections and Douglas-Rachford for Sparse Affine Feasibility

The problem of finding a vector with the fewest nonzero elements that satisfies an underdetermined system of linear equations is an NP-complete problem that is typically solved numerically via convex heuristics or nicely-behaved nonconvex relaxations. In this work we consider elementary methods based on projections for solving a sparse feasibility problem without employing convex heuristics. In a recent paper Bauschke, Luke, Phan and Wang (2014) showed that, locally, the fundamental method of alternating projections must converge linearly to a solution to the sparse feasibility problem with an affine constraint. In this paper we apply different analytical tools that allow us to show global linear convergence of alternating projections under familiar constraint qualifications. These analytical tools can also be applied to other algorithms. This is demonstrated with the prominent Douglas-Rachford algorithm where we establish local linear convergence of this method applied to the sparse affine feasibility problem.Comment: 29 pages, 2 figures, 37 references. Much expanded version from last submission. Title changed to reflect new development