Functional Gaussian graphical regression models for air quality data

In this paper, the scale response functional multivariate regression model is considered. By using the basis functions representation of functional predictors and regression coefficients, this model is rewritten as a multivariate regression model. This representation of the functional multivariate regression model is used for multiclass classification for multivariate functional data. Computational experiments performed on real labelled data sets demonstrate the effectiveness of the proposed method for classification for functional data.

We propose nonparametric methods for functional linear regression which are designed for sparse longitudinal data, where both the predictor and response are functions of a covariate such as time. Predictor and response processes have smooth random trajectories, and the data consist of a small number of noisy repeated measurements made at irregular times for a sample of subjects. In longitudinal studies, the number of repeated measurements per subject is often small and may be modeled as a discrete random number and, accordingly, only a finite and asymptotically nonincreasing number of measurements are available for each subject or experimental unit. We propose a functional regression approach for this situation, using functional principal component analysis, where we estimate the functional principal component scores through conditional expectations. This allows the prediction of an unobserved response trajectory from sparse measurements of a predictor trajectory. The resulting technique is flexible and allows for different patterns regarding the timing of the measurements obtained for predictor and response trajectories. Asymptotic properties for a sample of n subjects are investigated under mild conditions, as n→∞, and we obtain consistent estimation for the regression function. Besides convergence results for the components of functional linear regression, such as the regression parameter function, we construct asymptotic pointwise confidence bands for the predicted trajectories. A functional coefficient of determination as a measure of the variance explained by the functional regression model is introduced, extending the standard R2 to the functional case. The proposed methods are illustrated with a simulation study, longitudinal primary biliary liver cirrhosis data and an analysis of the longitudinal relationship between blood pressure and body mass index.

This paper introduces a MATLAB toolbox, MGraph, which applies graphical models as a natural environment to formulate and solve problems in microarray data analysis. MGraph with its graphical interface allows the user to predict genetic regulatory networks by a graphical gaussian model (GGM), and to quantify the effects of different experimental treatment conditions on gene expression profiles by a graphical log-linear model (GLM). The power of graphical models was explored and illustrated through two example applications. First, four MAPK pathways in yeast were meaningfully reconstructed through GGM. Second, GLM was used to quantify the contributions of sex, genotype and age to transcriptional variance in Drosophila melanogaster. This application may provide a valuable aid in the prediction of genetic regulatory networks, as well as in investigations of various experimental conditions that affect global gene expression profiles. The MATLAB program MGraph is freely available at http://www.uio.no/~junbaiw/mgraph/mgraph.html for academics.

We propose Bayesian methods for Gaussian graphical models that lead to sparse and adaptively shrunk estimators of the precision (inverse covariance) matrix. Our methods are based on lasso-type regularization priors leading to parsimonious parameterization of the precision matrix, which is essential in several applications involving learning relationships among the variables. In this context, we introduce a novel type of selection prior that develops a sparse structure on the precision matrix by making most of the elements exactly zero, in addition to ensuring positive definiteness - thus conducting model selection and estimation simultaneously. More importantly, we extend these methods to analyze clustered data using finite mixtures of Gaussian graphical model and infinite mixtures of Gaussian graphical models. We discuss appropriate posterior simulation schemes to implement posterior inference in the proposed models, including the evaluation of normalizing constants that are functions of parameters of interest, which result from the restriction of positive definiteness on the correlation matrix. We evaluate the operating characteristics of our method via several simulations and demonstrate the application to real data examples in genomics.

The inference and modeling of network‐like structures in genomic data is of prime importance in systems biology. Complex stochastic associations and interdependencies can very generally be described as a graphical model. However, the paucity of available samples in current high‐throughput experiments renders learning graphical models from genome data, such as microarray expression profiles, a challenging and very hard problem. Here we review several recently developed approaches to small‐sample inference of graphical Gaussian modeling and discuss strategies to cope with the high dimensionality of functional genomics data. Particular emphasis is put on regularization methods and an empirical Bayes network inference procedure.

In machine learning-based fractional cover estimation, the fractional cover distribution in training samples critically influences model construction and, consequently the accuracy of the estimations. While some studies have descriptively compared the accuracies of machine learning-based estimations across training sets derived from different sampling methods, a significant gap remains in quantitatively analyzing how the fractional cover distribution in training samples affects accuracy. This study aims to bridge this gap by introducing descriptors for fractional cover distribution in the training set and establishing mathematical relationships between these descriptors and the accuracy of fractional cover estimation. We employed the Dirichlet distribution to characterize the joint fractional cover of multiple land classes and the Beta distribution for single-class cover. Subsequently, two descriptors were developed: the Kullback-Leibler (KL) divergence, measuring the similarity of fractional cover distributions for the target class between the training and test sets, and the geometric angle, representing the fractional cover distributions of the target class in the training set at the same KL divergence. Fractional cover estimation was performed using random forest regression, with accuracy assessed on an independent test set. The relationships between the KL divergence and accuracy, and between the geometric angle and accuracy at the same KL divergence, were modeled using univariate linear models and harmonic models, respectively. The combined effects of these descriptors on accuracy were further analyzed using coupled harmonic analysis and generalized additive models. Our experimental results, using both simulated and real data, demonstrated the effectiveness of these models. Given the strong explanatory power of the KL divergence in the accuracy of fractional cover estimation, we encourage researchers to report detailed statistical information of both training and test sets, enriching the understanding of model performance in fractional cover estimation.

Gene regulatory networks (GRNs) are often inferred based on Gaussian graphical models that could identify the conditional dependence among genes by estimating the corresponding precision matrix. Classical Gaussian graphical models are usually designed for single network estimation and ignore existing knowledge such as pathway information. Therefore, they can neither make use of the common information shared by multiple networks, nor can they utilize useful prior information to guide the estimation. In this paper, we propose a new weighted fused pathway graphical lasso (WFPGL) to jointly estimate multiple networks by incorporating prior knowledge derived from known pathways and gene interactions. Based on the assumption that two genes are less likely to be connected if they do not participate together in any pathways, a pathway-based constraint is considered in our model. Moreover, we introduce a weighted fused lasso penalty in our model to take into account prior gene interaction data and common information shared by multiple networks. Our model is optimized based on the alternating direction method of multipliers (ADMM). Experiments on synthetic data demonstrate that our method outperforms other five state-of-the-art graphical models. We then apply our model to two real datasets. Hub genes in our identified state-specific networks show some shared and specific patterns, which indicates the efficiency of our model in revealing the underlying mechanisms of complex diseases.

In genomics, it is often of interest to study the structural change of a genetic network between two phenotypes. Under Gaussian graphical models, the problem can be transformed to estimating the difference between two precision matrices, and several approaches have been recently developed for this task such as joint graphical lasso and fused graphical lasso. However, the multivariate Gaussian assumptions made in the existing approaches are often violated in reality. For instance, most RNA‐Seq data follow non‐Gaussian distributions even after log‐transformation or other variance‐stabilizing transformations. In this work, we consider the problem of directly estimating differential networks under a flexible semiparametric model, namely the nonparanormal graphical model, where the random variables are assumed to follow a multivariate Gaussian distribution after a set of monotonically increasing transformations. We propose to use a novel rank‐based estimator to directly estimate the differential network, together with a parametric simplex algorithm for fast implementation. Theoretical properties of the new estimator are established under a high‐dimensional setting where grows with almost exponentially fast. In particular, we show that the proposed estimator is consistent in both parameter estimation and support recovery. Both synthetic data and real genomic data are used to illustrate the promise of the new approach.The Canadian Journal of Statistics48: 187–203; 2020 © 2019 Statistical Society of Canada

BackgroundDSC is used to determine thermally-induced conformational changes of biomolecules within a blood plasma sample. Recent research has indicated that DSC curves (or thermograms) may have different characteristics based on disease status and, thus, may be useful as a monitoring and diagnostic tool for some diseases. Since thermograms are curves measured over a range of temperature values, they are considered functional data. In this paper we apply functional data analysis techniques to analyze differential scanning calorimetry (DSC) data from individuals from the Lupus Family Registry and Repository (LFRR). The aim was to assess the effect of lupus disease status as well as additional covariates on the thermogram profiles, and use FD analysis methods to create models for classifying lupus vs. control patients on the basis of the thermogram curves.MethodsThermograms were collected for 300 lupus patients and 300 controls without lupus who were matched with diseased individuals based on sex, race, and age. First, functional regression with a functional response (DSC) and categorical predictor (disease status) was used to determine how thermogram curve structure varied according to disease status and other covariates including sex, race, and year of birth. Next, functional logistic regression with disease status as the response and functional principal component analysis (FPCA) scores as the predictors was used to model the effect of thermogram structure on disease status prediction. The prediction accuracy for patients with Osteoarthritis and Rheumatoid Arthritis but without Lupus was also calculated to determine the ability of the classifier to differentiate between Lupus and other diseases. Data were divided 1000 times into separate 2/3 training and 1/3 test data for evaluation of predictions. Finally, derivatives of thermogram curves were included in the models to determine whether they aided in prediction of disease status.ResultsFunctional regression with thermogram as a functional response and disease status as predictor showed a clear separation in thermogram curve structure between cases and controls. The logistic regression model with FPCA scores as the predictors gave the most accurate results with a mean 79.22% correct classification rate with a mean sensitivity = 79.70%, and specificity = 81.48%. The model correctly classified OA and RA patients without Lupus as controls at a rate of 75.92% on average with a mean sensitivity = 79.70% and specificity = 77.6%. Regression models including FPCA scores for derivative curves did not perform as well, nor did regression models including covariates.ConclusionChanges in thermograms observed in the disease state likely reflect covalent modifications of plasma proteins or changes in large protein-protein interacting networks resulting in the stabilization of plasma proteins towards thermal denaturation. By relating functional principal components from thermograms to disease status, our Functional Principal Component Analysis model provides results that are more easily interpretable compared to prior studies. Further, the model could also potentially be coupled with other biomarkers to improve diagnostic classification for lupus.

This study examines the optimal selections of bandwidth and semi-metric for a functional partial linear model. Our proposed method begins by estimating the unknown error density using a kernel density estimator of residuals, where the regression function, consisting of parametric and nonparametric components, can be estimated by functional principal component and functional Nadayara-Watson estimators. The estimation accuracy of the regression function and error density crucially depends on the optimal estimations of bandwidth and semi-metric. A Bayesian method is utilized to simultaneously estimate the bandwidths in the regression function and kernel error density by minimizing the Kullback-Leibler divergence. For estimating the regression function and error density, a series of simulation studies demonstrate that the functional partial linear model gives improved estimation and forecast accuracies compared with the functional principal component regression and functional nonparametric regression. Using a spectroscopy dataset, the functional partial linear model yields better forecast accuracy than some commonly used functional regression models. As a by-product of the Bayesian method, a pointwise prediction interval can be obtained, and marginal likelihood can be used to select the optimal semi-metric.

BackgroundEpistasis plays an essential rule in understanding the regulation mechanisms and is an essential component of the genetic architecture of the gene expressions. However, interaction analysis of gene expressions remains fundamentally unexplored due to great computational challenges and data availability. Due to variation in splicing, transcription start sites, polyadenylation sites, post-transcriptional RNA editing across the entire gene, and transcription rates of the cells, RNA-seq measurements generate large expression variability and collectively create the observed position level read count curves. A single number for measuring gene expression which is widely used for microarray measured gene expression analysis is highly unlikely to sufficiently account for large expression variation across the gene. Simultaneously analyzing epistatic architecture using the RNA-seq and whole genome sequencing (WGS) data poses enormous challenges.MethodsWe develop a nonlinear functional regression model (FRGM) with functional responses where the position-level read counts within a gene are taken as a function of genomic position, and functional predictors where genotype profiles are viewed as a function of genomic position, for epistasis analysis with RNA-seq data. Instead of testing the interaction of all possible pair-wises SNPs, the FRGM takes a gene as a basic unit for epistasis analysis, which tests for the interaction of all possible pairs of genes and use all the information that can be accessed to collectively test interaction between all possible pairs of SNPs within two genome regions.ResultsBy large-scale simulations, we demonstrate that the proposed FRGM for epistasis analysis can achieve the correct type 1 error and has higher power to detect the interactions between genes than the existing methods. The proposed methods are applied to the RNA-seq and WGS data from the 1000 Genome Project. The numbers of pairs of significantly interacting genes after Bonferroni correction identified using FRGM, RPKM and DESeq were 16,2361, 260 and 51, respectively, from the 350 European samples.ConclusionsThe proposed FRGM for epistasis analysis of RNA-seq can capture isoform and position-level information and will have a broad application. Both simulations and real data analysis highlight the potential for the FRGM to be a good choice of the epistatic analysis with sequencing data.

Loss function, unbiasedness, and optimality of Gaussian graphical model selection

SummaryIn recent years, there has been a significant increase in scholarly research on transfer learning. This review provides an in‐depth examination of statistical transfer learning, categorising challenges into two domains: model‐based and data distribution‐based transfer learning. For model‐based transfer learning, we assume sufficient similarity between the source and target domain models, which allows the effective use of source data for target tasks. This framework applies to various problems, including (generalised) linear regression, quantile regression, kernel regression, functional regression and graphical model. From another point of view, data distribution‐based transfer learning addresses variations due to covariate shift and posterior drift, enhancing the reliability of shared data from diverse sources. The primary objective is to introduce typical methods and data structures adapted for transfer learning, along with resolution techniques. Additionally, we elucidate theoretical concepts such as consistency and minimax optimality to provide a comprehensive understanding of the subject. Furthermore, we explore other related topics in statistical transfer learning that tackle various problems.

Checking the adequacy of functional linear quantile regression model

Functional linear regression models have been widely used in the gene association analysis of complex traits. These models retain all the genetic information in the data and take full advantage of spatial information in genetic variation data, which leads to brilliant detection power. However, the significant association signals identified by the high-power methods are not all the real causal SNPs, because it is easy to regard noise information as significant association signals, leading to a false association. In this paper, a method based on the sparse functional data association test (SFDAT) of gene region association analysis is developed based on a functional linear regression model with local sparse estimation. The evaluation indicators CSR and DL are defined to evaluate the feasibility and performance of the proposed method with other indicators. Simulation studies show that: (1) SFDAT performs well under both linkage equilibrium and linkage disequilibrium simulation; (2) SFDAT performs successfully for gene regions (including common variants, low-frequency variants, rare variants and mix variants); (3) With power and type I error rates comparable to OLS and Smooth, SFDAT has a better ability to handle the zero regions. The Oryza sativa data set is analyzed by SFDAT. It is shown that SFDAT can better perform gene association analysis and eliminate the false positive of gene localization. This study showed that SFDAT can lower the interference caused by noise while maintaining high power. SFDAT provides a new method for the association analysis between gene regions and phenotypic quantitative traits.