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Register a new userGaussian process regression for survival data with competing risks
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James Barrett
Publication date
2013
fields
Mathematical Statistics
and research's language is
English
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We apply Gaussian process (GP) regression, which provides a powerful non-parametric probabilistic method of relating inputs to outputs, to survival data consisting of time-to-event and covariate measurements. In this context, the covariates are regarded as the `inputs and the event times are the `outputs. This allows for highly flexible inference of non-linear relationships between covariates and event times. Many existing methods, such as the ubiquitous Cox proportional hazards model, focus primarily on the hazard rate which is typically assumed to take some parametric or semi-parametric form. Our proposed model belongs to the class of accelerated failure time models where we focus on directly characterising the relationship between covariates and event times without any explicit assumptions on what form the hazard rates take. It is straightforward to include various types and combinations of censored and truncated observations. We apply our approach to both simulated and experimental data. We then apply multiple output GP regression, which can handle multiple potentially correlated outputs for each input, to competing risks survival data where multiple event types can occur. By tuning one of the model parameters we can control the extent to which the multiple outputs (the time-to-event for each risk) are dependent thus allowing the specification of correlated risks. Simulation studies suggest that in some cases assuming dependence can lead to more accurate predictions.
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The analysis of high dimensional survival data is challenging, primarily due to the problem of overfitting which occurs when spurious relationships are inferred from data that subsequently fail to exist in test data. Here we propose a novel method of extracting a low dimensional representation of covariates in survival data by combining the popular Gaussian Process Latent Variable Model (GPLVM) with a Weibull Proportional Hazards Model (WPHM). The combined model offers a flexible non-linear probabilistic method of detecting and extracting any intrinsic low dimensional structure from high dimensional data. By reducing the covariate dimension we aim to diminish the risk of overfitting and increase the robustness and accuracy with which we infer relationships between covariates and survival outcomes. In addition, we can simultaneously combine information from multiple data sources by expressing multiple datasets in terms of the same low dimensional space. We present results from several simulation studies that illustrate a reduction in overfitting and an increase in predictive performance, as well as successful detection of intrinsic dimensionality. We provide evidence that it is advantageous to combine dimensionality reduction with survival outcomes rather than performing unsupervised dimensionality reduction on its own. Finally, we use our model to analyse experimental gene expression data and detect and extract a low dimensional representation that allows us to distinguish high and low risk groups with superior accuracy compared to doing regression on the original high dimensional data.
Gaussian process regression (GPR) model is a popular nonparametric regression model. In GPR, features of the regression function such as varying degrees of smoothness and periodicities are modeled through combining various covarinace kernels, which are supposed to model certain effects. The covariance kernels have unknown parameters which are estimated by the EM-algorithm or Markov Chain Monte Carlo. The estimated parameters are keys to the inference of the features of the regression functions, but identifiability of these parameters has not been investigated. In this paper, we prove identifiability of covariance kernel parameters in two radial basis mixed kernel GPR and radial basis and periodic mixed kernel GPR. We also provide some examples about non-identifiable cases in such mixed kernel GPRs.
Gaussian processes (GP) are widely used as a metamodel for emulating time-consuming computer codes. We focus on problems involving categorical inputs, with a potentially large number L of levels (typically several tens), partitioned in G << L groups of various sizes. Parsimonious covariance functions, or kernels, can then be defined by block covariance matrices T with constant covariances between pairs of blocks and within blocks. We study the positive definiteness of such matrices to encourage their practical use. The hierarchical group/level structure, equivalent to a nested Bayesian linear model, provides a parameterization of valid block matrices T. The same model can then be used when the assumption within blocks is relaxed, giving a flexible parametric family of valid covariance matrices with constant covariances between pairs of blocks. The positive definiteness of T is equivalent to the positive definiteness of a smaller matrix of size G, obtained by averaging each block. The model is applied to a problem in nuclear waste analysis, where one of the categorical inputs is atomic number, which has more than 90 levels.
Penalization procedures often suffer from their dependence on multiplying factors, whose optimal values are either unknown or hard to estimate from the data. We propose a completely data-driven calibration algorithm for this parameter in the least-squares regression framework, without assuming a particular shape for the penalty. Our algorithm relies on the concept of minimal penalty, recently introduced by Birge and Massart (2007) in the context of penalized least squares for Gaussian homoscedastic regression. On the positive side, the minimal penalty can be evaluated from the data themselves, leading to a data-driven estimation of an optimal penalty which can be used in practice; on the negative side, their approach heavily relies on the homoscedastic Gaussian nature of their stochastic framework. The purpose of this paper is twofold: stating a more general heuristics for designing a data-driven penalty (the slope heuristics) and proving that it works for penalized least-squares regression with a random design, even for heteroscedastic non-Gaussian data. For technical reasons, some exact mathematical results will be proved only for regressogram bin-width selection. This is at least a first step towards further results, since the approach and the method that we use are indeed general.
Survival analysis in the presence of multiple possible adverse events, i.e., competing risks, is a pervasive problem in many industries (healthcare, finance, etc.). Since only one event is typically observed, the incidence of an event of interest is often obscured by other related competing events. This nonidentifiability, or inability to estimate true cause-specific survival curves from empirical data, further complicates competing risk survival analysis. We introduce Siamese Survival Prognosis Network (SSPN), a novel deep learning architecture for estimating personalized risk scores in the presence of competing risks. SSPN circumvents the nonidentifiability problem by avoiding the estimation of cause-specific survival curves and instead determines pairwise concordant time-dependent risks, where longer event times are assigned lower risks. Furthermore, SSPN is able to directly optimize an approximation to the C-discrimination index, rather than relying on well-known metrics which are unable to capture the unique requirements of survival analysis with competing risks.
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