Improved modeling of clinical data with kernel methods

Objective: Despite the rise of high-throughput technologies, clinical data such as age, gender and medical history guide clinical management for most diseases and examinations. To improve clinical management, available patient information should be fully exploited. This requires appropriate modeling of relevant parameters. Methods: When kernel methods are used, traditional kernel functions such as the linear kernel are often applied to the set of clinical parameters. These kernel functions, however, have their disadvantages due to the specific characteristics of clinical data, being a mix of variable types with each variable its own range. We propose a new kernel function specifically adapted to the characteristics of clinical data. Results: The clinical kernel function provides a better representation of patients' similarity by equalizing the influence of all variables and taking into account the range r of the variables. Moreover, it is robust with respect to changes in r. Incorporated in a least squares support vector machine, the new kernel function results in significantly improved diagnosis, prognosis and prediction of therapy response. This is illustrated on four clinical data sets within gynecology, with an average increase in test area under the ROC curve (AUC) of 0.023, 0.021, 0.122 and 0.019, respectively. Moreover, when combining clinical parameters and expression data in three case studies on breast cancer, results improved overall with use of the new kernel function and when considering both data types in a weighted fashion, with a larger weight assigned to the clinical parameters. The increase in AUC with respect to a standard kernel function and/or unweighted data combination was maximum 0.127, 0.042 and 0.118 for the three case studies. Conclusion: For clinical data consisting of variables of different types, the proposed kernel function which takes into account the type and range of each variable - has shown to be a better alternative for linear and non-linear classification problems. (C) 2011 Elsevier B.V. All rights reserved

Kernel Methods and Measures for Classification with Transparency, Interpretability and Accuracy in Health Care

Support vector machines are a popular method in machine learning. They learn from data about a subject, for example, lung tumors in a set of patients, to classify new data, such as, a new patient’s tumor. The new tumor is classified as either cancerous or benign, depending on how similar it is to the tumors of other patients in those two classes—where similarity is judged by a kernel. The adoption and use of support vector machines in health care, however, is inhibited by a perceived and actual lack of rationale, understanding and transparency for how they work and how to interpret information and results from them. For example, a user must select the kernel, or similarity function, to be used, and there are many kernels to choose from but little to no useful guidance on choosing one. The primary goal of this thesis is to create accurate, transparent and interpretable kernels with rationale to select them for classification in health care using SVM—and to do so within a theoretical framework that advances rationale, understanding and transparency for kernel/model selection with atomic data types. The kernels and framework necessarily co-exist. The secondary goal of this thesis is to quantitatively measure model interpretability for kernel/model selection and identify the types of interpretable information which are available from different models for interpretation. Testing my framework and transparent kernels with empirical data I achieve classification accuracy that is better than or equivalent to the Gaussian RBF kernels. I also validate some of the model interpretability measures I propose