Generalized structured additive regression based on Bayesian P-splines

Generalized additive models (GAM) for modelling nonlinear effects of continuous covariates are now well established tools for the applied statistician. In this paper we develop Bayesian GAM's and extensions to generalized structured additive regression based on one or two dimensional P-splines as the main building block. The approach extends previous work by Lang und Brezger (2003) for Gaussian responses. Inference relies on Markov chain Monte Carlo (MCMC) simulation techniques, and is either based on iteratively weighted least squares (IWLS) proposals or on latent utility representations of (multi)categorical regression models. Our approach covers the most common univariate response distributions, e.g. the Binomial, Poisson or Gamma distribution, as well as multicategorical responses. For the first time, we present Bayesian semiparametric inference for the widely used multinomial logit models. As we will demonstrate through two applications on the forest health status of trees and a space-time analysis of health insurance data, the approach allows realistic modelling of complex problems. We consider the enormous flexibility and extendability of our approach as a main advantage of Bayesian inference based on MCMC techniques compared to more traditional approaches. Software for the methodology presented in the paper is provided within the public domain package BayesX

Structured penalized regression for drug sensitivity prediction

Large-scale {\it in vitro} drug sensitivity screens are an important tool in personalized oncology to predict the effectiveness of potential cancer drugs. The prediction of the sensitivity of cancer cell lines to a panel of drugs is a multivariate regression problem with high-dimensional heterogeneous multi-omics data as input data and with potentially strong correlations between the outcome variables which represent the sensitivity to the different drugs. We propose a joint penalized regression approach with structured penalty terms which allow us to utilize the correlation structure between drugs with group-lasso-type penalties and at the same time address the heterogeneity between omics data sources by introducing data-source-specific penalty factors to penalize different data sources differently. By combining integrative penalty factors (IPF) with tree-guided group lasso, we create the IPF-tree-lasso method. We present a unified framework to transform more general IPF-type methods to the original penalized method. Because the structured penalty terms have multiple parameters, we demonstrate how the interval-search Efficient Parameter Selection via Global Optimization (EPSGO) algorithm can be used to optimize multiple penalty parameters efficiently. Simulation studies show that IPF-tree-lasso can improve the prediction performance compared to other lasso-type methods, in particular for heterogenous data sources. Finally, we employ the new methods to analyse data from the Genomics of Drug Sensitivity in Cancer project.Comment: Zhao Z, Zucknick M (2020). Structured penalized regression for drug sensitivity prediction. Journal of the Royal Statistical Society, Series C. 19 pages, 6 figures and 2 table

Structured additive regression for multicategorical space-time data: A mixed model approach

In many practical situations, simple regression models suffer from the fact that the dependence of responses on covariates can not be sufficiently described by a purely parametric predictor. For example effects of continuous covariates may be nonlinear or complex interactions between covariates may be present. A specific problem of space-time data is that observations are in general spatially and/or temporally correlated. Moreover, unobserved heterogeneity between individuals or units may be present. While, in recent years, there has been a lot of work in this area dealing with univariate response models, only limited attention has been given to models for multicategorical space-time data. We propose a general class of structured additive regression models (STAR) for multicategorical responses, allowing for a flexible semiparametric predictor. This class includes models for multinomial responses with unordered categories as well as models for ordinal responses. Non-linear effects of continuous covariates, time trends and interactions between continuous covariates are modelled through Bayesian versions of penalized splines and flexible seasonal components. Spatial effects can be estimated based on Markov random fields, stationary Gaussian random fields or two-dimensional penalized splines. We present our approach from a Bayesian perspective, allowing to treat all functions and effects within a unified general framework by assigning appropriate priors with different forms and degrees of smoothness. Inference is performed on the basis of a multicategorical linear mixed model representation. This can be viewed as posterior mode estimation and is closely related to penalized likelihood estimation in a frequentist setting. Variance components, corresponding to inverse smoothing parameters, are then estimated by using restricted maximum likelihood. Numerically efficient algorithms allow computations even for fairly large data sets. As a typical example we present results on an analysis of data from a forest health survey

Penalized additive regression for space-time data: a Bayesian perspective

We propose extensions of penalized spline generalized additive models for analysing space-time regression data and study them from a Bayesian perspective. Non-linear effects of continuous covariates and time trends are modelled through Bayesian versions of penalized splines, while correlated spatial effects follow a Markov random field prior. This allows to treat all functions and effects within a unified general framework by assigning appropriate priors with different forms and degrees of smoothness. Inference can be performed either with full (FB) or empirical Bayes (EB) posterior analysis. FB inference using MCMC techniques is a slight extension of own previous work. For EB inference, a computationally efficient solution is developed on the basis of a generalized linear mixed model representation. The second approach can be viewed as posterior mode estimation and is closely related to penalized likelihood estimation in a frequentist setting. Variance components, corresponding to smoothing parameters, are then estimated by using marginal likelihood. We carefully compare both inferential procedures in simulation studies and illustrate them through real data applications. The methodology is available in the open domain statistical package BayesX and as an S-plus/R function