Item response theory modeling for microarray gene expression data

Latent variable (LV) models are increasingly being used in environmental epidemiology as a way to summarize multiple environmental exposures and thus minimize statistical concerns that arise in multiple regression. LV models may be especially useful when multivariate exposures are collected repeatedly over time. LV models can accommodate a variety of assumptions but, at the same time, present the user with many choices for model specification particularly in the case of exposure data collected repeatedly over time. For instance, the user could assume conditional independence of observed exposure biomarkers given the latent exposure and, in the case of longitudinal latent exposure variables, time invariance of the measurement model. Choosing which assumptions to relax is not always straightforward. We were motivated by a study of prenatal lead exposure and mental development, where assumptions of the measurement model for the time-changing longitudinal exposure have appreciable impact on (maximum-likelihood) inferences about the health effects of lead exposure. Although we were not particularly interested in characterizing the change of the LV itself, imposing a longitudinal LV structure on the repeated multivariate exposure measures could result in high efficiency gains for the exposure-disease association. We examine the biases of maximum likelihood estimators when assumptions about the measurement model for the longitudinal latent exposure variable are violated. We adapt existing instrumental variable estimators to the case of longitudinal exposures and propose them as an alternative to estimate the health effects of a time-changing latent predictor. We show that instrumental variable estimators remain unbiased for a wide range of data generating models and have advantages in terms of mean squared error. Copyright © 2017 John Wiley & Sons, Ltd.

The real-time system of the JT-60 has a cascade structure with the major and the minor control loops. The multi-variable feedback control is adopted in the major control loop in order to adjust non-linear effects which will appear in the high-/beta/region. By applying the concept of 'phase shift control' to the control program of the major control loop, a flexible tokamak discharge control is expected to be performed with taking account of machine protection.

Microarray experiments are proficient of yielding observations for thousands of genes those are differentially expressed under several conditions. Although it is possible to measure simultaneously the changes in gene expression profiles at whole genomic scale, interpreting individual gene expression profile in terms of its actual biological function or associated biochemical processes remains challenging. Exploratory multivariate statistical techniques such as principal component analysis have been extensively used to reduce the complexity of large size microarray data. Although Saccaromycea Cerevisae is the most widely studied species using microarray techniques, a complete understanding of the efficacy of principal component analysis and data pre-processing is still lacking for clustering and functional mapping of yeast gene expression profiles, reported in various studies. Therefore in this work, we evaluate the impact of data pre-processing and principal component analysis on k-means clustering-based functional mapping of yeast gene expression profiles observed during diauxic-shift. Two time-series gene expression datasets were chosen such as, (1) yeast diauxic-shift data and (2) yeast sporulation data to examine the efficacy of principal component analysis in interpreting gene-based or score-based clusters and their relationship with known pathways. It was shown that unlike conventional pre-processing, principal component analysis provides a powerful tool to capture most of the information using only two component variables for inferring gene expression time-course data. Using yeast genome databases, it was demonstrated that clustering with principal components instead of the original variables does not necessarily improve the cluster quality but helps in identifying the relationships between genes of a cluster and key biological process of diauxic shift. Overall, the present analysis is useful in mining high dimensional microarray data at a reduced computational cost associated with functional enrichment of expression time-series, regardless of species or experimental conditions.

There are a large number of high-dimensional data in the Internet of Brain Things, and the data is reduced from the high-dimensional to low-dimensional to maintain the similarity between the data, thereby effectively ensuring the operating speed of the Internet of Brain Things. In the traditional method, the distributed dimensionality reduction reconstruction algorithm of the High dimensional data has poor dimensionality reduction effect and serious data distortion after reconstruction. A method for dimensionality reconstruction of high-dimensional data in the Internet of Brain Things is proposed. By using the algorithm of linear discriminant analysis, the projection matrix of high dimensional data is constructed to solve it. According to the solution results, using improved implicit variable model to establish a high dimensional large data dimensionality reduction model for the Internet of Brain Things. The fitness value of data after dimensionality reduction is calculated by quantum immune clonal algorithm, and the optimal individual and optimal solution are determined. The data reconfiguration is realized through the optimal solution marshalling. Experimental results show that the proposed algorithm can effectively improve the dimensionality reduction of High dimensional data in the Internet of Brain Things. After reconstruction, the reconstructed data retain accurate data information, the reliability of reconstructed data is high, and the computational complexity is not high, the need for small storage space, and the advantages of strong promotion ability.

In this chapter, we address distributed learning algorithms for statistical latent variable models, with a focus on topic models. Many high-dimensional datasets, such as text corpora and image databases, are too large to allow one to learn topic models on a single computer. Moreover, a growing number of applications require that inference be fast or in real time, motivating the exploration of parallel and distributed learning algorithms. We begin by reviewing topic models such as Latent Dirichlet Allocation and Hierarchical Dirichlet Processes. We discuss parallel and distributed algorithms for learning these models and show that these algorithms can achieve substantial speedups without sacrificing model quality. Next we discuss practical guidelines for running our algorithms within various parallel computing frameworks and highlight complementary speedup techniques. Finally, we generalize our distributed approach to handle Bayesian networks. Several of the results in this chapter have appeared in previous papers in the specific context of topic modeling. The goal of this chapter is to present a comprehensive overview of distributed inference algorithms and to extend the general ideas to a broader class of Bayesian networks. Latent Variable Models Latent variable models are a class of statistical models that explain observed data with latent (or hidden) variables. Topic models and hidden Markov models are two examples of such models, where the latent variables are the topic assignment variables and the hidden states, respectively. Given observed data, the goal is to perform Bayesian inference over the latent variables and use the learned model to make inferences or predictions.

Microarrays have now gone from obscurity to being almost ubiquitous in biological research. At the same time, the statistical methodology for microarray analysis has progressed from simple visual assessments of results to novel algorithms for analyzing changes in expression profiles. In a micro-RNA (miRNA) or gene-expression profiling experiment, the expression levels of thousands of genes/miRNAs are simultaneously monitored to study the effects of certain treatments, diseases, and developmental stages on their expressions. Microarray-based gene expression profiling can be used to identify genes, whose expressions are changed in response to pathogens or other organisms by comparing gene expression in infected to that in uninfected cells or tissues. Recent studies have revealed that patterns of altered microarray expression profiles in cancer can serve as molecular biomarkers for tumor diagnosis, prognosis of disease-specific outcomes, and prediction of therapeutic responses. Microarray data sets containing expression profiles of a number of miRNAs or genes are used to identify biomarkers, which have dysregulation in normal and malignant tissues. However, small sample size remains a bottleneck to design successful classification methods. On the other hand, adequate number of microarray data that do not have clinical knowledge can be employed as additional source of information. In this paper, a combination of kernelized fuzzy rough set (KFRS) and semisupervised support vector machine (S3VM) is proposed for predicting cancer biomarkers from one miRNA and three gene expression data sets. Biomarkers are discovered employing three feature selection methods, including KFRS. The effectiveness of the proposed KFRS and S3VM combination on the microarray data sets is demonstrated, and the cancer biomarkers identified from miRNA data are reported. Furthermore, biological significance tests are conducted for miRNA cancer biomarkers.

Classification of tumors into subtypes can inform personalized approaches to treatment including the choice of targeted therapies. The two most common lung cancer histological subtypes, lung adenocarcinoma and lung squamous cell carcinoma, have been previously divided into transcriptional subtypes using microarray data, and corresponding signatures were subsequently used to classify RNA-seq data. Cross-platform unsupervised classification facilitates the identification of robust transcriptional subtypes by combining vast amounts of publicly available microarray and RNA-seq data. However, cross-platform classification is challenging because of intrinsic differences in data generated using the two gene expression profiling technologies. In this report, we show that robust gene expression subtypes can be identified in integrated data representing over 3500 normal and tumor lung samples profiled using two widely used platforms, Affymetrix HG-U133 Plus 2.0 Array and Illumina HiSeq RNA sequencing. We tested and analyzed consensus clustering for 384 combinations of data processing methods. The agreement between subtypes identified in single-platform and cross-platform normalized data was then evaluated using a variety of statistics. Results show that unsupervised learning can be achieved with combined microarray and RNA-seq data using selected preprocessing, cross-platform normalization, and unsupervised feature selection methods. Our analysis confirmed three lung adenocarcinoma transcriptional subtypes, but only two consistent subtypes in squamous cell carcinoma, as opposed to four subtypes previously identified. Further analysis showed that tumor subtypes were associated with distinct patterns of genomic alterations in genes coding for therapeutic targets. Importantly, by integrating quantitative proteomics data, we were able to identify tumor subtype biomarkers that effectively classify samples on the basis of both gene and protein expression. This study provides the basis for further integrative data analysis across gene and protein expression profiling platforms.

Noisy, high-dimensional time series observations can often be described by a set of low-dimensional latent variables. Commonly used methods to extract these latent variables typically assume instantaneous relationships between the latent and observed variables. In many physical systems, changes in the latent variables manifest as changes in the observed variables after time delays. Techniques that do not account for these delays can recover a larger number of latent variables than are present in the system, thereby making the latent representation more difficult to interpret. In this work, we introduce a novel probabilistic technique, time-delay gaussian-process factor analysis (TD-GPFA), that performs dimensionality reduction in the presence of a different time delay between each pair of latent and observed variables. We demonstrate how using a gaussian process to model the evolution of each latent variable allows us to tractably learn these delays over a continuous domain. Additionally, we show how TD-GPFA combines temporal smoothing and dimensionality reduction into a common probabilistic framework. We present an expectation/conditional maximization either (ECME) algorithm to learn the model parameters. Our simulations demonstrate that when time delays are present, TD-GPFA is able to correctly identify these delays and recover the latent space. We then applied TD-GPFA to the activity of tens of neurons recorded simultaneously in the macaque motor cortex during a reaching task. TD-GPFA is able to better describe the neural activity using a more parsimonious latent space than GPFA, a method that has been used to interpret motor cortex data but does not account for time delays. More broadly, TD-GPFA can help to unravel the mechanisms underlying high-dimensional time series data by taking into account physical delays in the system.

Often quantities of interest in psychology cannot be observed directly. These unobservable quantities, known as latent variables, tend to be complex, often multidimensional, constructs. In many cases these constructs are categorical, such that individuals belong to mutually exclusive and exhaustive unobservable subgroups. Latent class analysis (LCA) is a statistical approach to modeling a discrete latent variable using multiple, discrete observed variables as indicators. Examples of latent class variables that appear in the psychology literature include temperament type, substance use behavior, teaching style, stages of change in the transtheoretical model, and latent classes of risk. The first section of this chapter provides a conceptual introduction to the concept of a latent class followed by a technical introduction to the mathematical model, including multiple-groups LCA and LCA with covariates. This is followed by a discussion of parameter restrictions, model selection, and goodness-of-fit. The second section demonstrates LCA using the empirical example of depression subtypes in adolescence. Five latent classes were identified based on responses to eight questionnaire items assessing depression symptoms: Non-depressed (characterized by a low probability of reporting all eight depression symptoms), sad, disliked, sad + disliked, and depressed (characterized by a high probability of reporting all eight depression symptoms). The third section presents longitudinal extensions of the model, including repeated-measures LCA and latent transition analysis (LTA). The empirical example is extended to examine change in depression subtypes over time. The final sections describe recent extensions to the latent class model and areas that merit additional research in the future. Keywords: latent class analysis; latent transition analysis; latent variable model; categorical data

High dimension and complexity of network high-dimensional data lead to poor feature selection effect network high-dimensional data. To effectively solve this problem, feature selection algorithms for high-dimensional network data based on supervised discriminant projection (SDP) have been designed. The sparse representation problem of high-dimensional network data is transformed into an Lp norm optimization problem, and the sparse subspace clustering method is used to cluster high-dimensional network data. Dimensionless processing is carried out for the clustering processing results. Based on the linear projection matrix and the best transformation matrix, the dimensionless processing results are reduced by combining the SDP. The sparse constraint method is used to achieve feature selection of high-dimensional data in the network, and the relevant feature selection results are obtained. The experimental findings demonstrate that the suggested algorithm can effectively cluster seven different types of data and converges when the number of iterations approaches 24. The F1 value, recall, and precision are all kept at high levels. High-dimensional network data feature selection accuracy on average is 96.9%, and feature selection time on average is 65.1 milliseconds. The selection effect for network high-dimensional data features is good.

Gene selection and classification using Taguchi chaotic binary particle swarm optimization

Purpose: Since oxidative stress involves a variety of cellular changes, no single biomarker can serve as a complete measure of this complex biological process. The analytic technique of structural equation modeling (SEM) provides a possible solution to this problem by modelling a latent (unobserved) variable constructed from the covariance of multiple biomarkers.Methods: Using three pooled datasets, we modelled a latent oxidative stress variable from five biomarkers related to oxidative stress: F2-isoprostanes (FIP), fluorescent oxidation products, mitochondrial DNA copy number, γ-tocopherol (Gtoc) and C-reactive protein (CRP, an inflammation marker closely linked to oxidative stress). We validated the latent variable by assessing its relation to pro- and anti-oxidant exposures.Results: FIP, Gtoc and CRP characterized the latent oxidative stress variable. Obesity, smoking, aspirin use and β-carotene were statistically significantly associated with oxidative stress in the theorized directions; the same exposures were weakly and inconsistently associated with the individual biomarkers.Conclusions: Our results suggest that using SEM with latent variables decreases the biomarker-specific variability, and may produce a better measure of oxidative stress than do single variables. This methodology can be applied to similar areas of research in which a single biomarker is not sufficient to fully describe a complex biological phenomenon.

Extending the traditional discrete choice model by incorporating latent psychological factors can help to better understand the individual’s decision-making process and therefore to yield more reliable part-worth estimates and market share predictions. Several integrated choice and latent variable (ICLV) models which merge the conditional logit model with a structural equation model exist in the literature. They assume homogeneity in the part-worths and use latent variables to model the heterogeneity among the respondents. This paper starts from the mixed logit model that describes the heterogeneity in the part-worths and uses the latent variables to decrease the unexplained part of the heterogeneity. The empirical study presented here shows these ICLV models perform very well with respect to model fit and prediction.

Measurement of non-random attrition effects on mobility rates using trip diaries data

It is well known that Affymetrix microarrays are widely used to predict genome-wide gene expression and genome-wide genetic polymorphisms from RNA and genomic DNA hybridization experiments, respectively. It has recently been proposed to integrate the two predictions by use of RNA microarray data only. Although the ability to detect single feature polymorphisms (SFPs) from RNA microarray data has many practical implications for genome study in both sequenced and unsequenced species, it raises enormous challenges for statistical modelling and analysis of microarray gene expression data for this objective. Several methods are proposed to predict SFPs from the gene expression profile. However, their performance is highly vulnerable to differential expression of genes. The SFPs thus predicted are eventually a reflection of differentially expressed genes rather than genuine sequence polymorphisms. To address the problem, we developed a novel statistical method to separate the binding affinity between a transcript and its targeting probe and the parameter measuring transcript abundance from perfect-match hybridization values of Affymetrix gene expression data. We implemented a Bayesian approach to detect SFPs and to genotype a segregating population at the detected SFPs. Based on analysis of three Affymetrix microarray datasets, we demonstrated that the present method confers a significantly improved robustness and accuracy in detecting the SFPs that carry genuine sequence polymorphisms when compared to its rivals in the literature. The method developed in this paper will provide experimental genomicists with advanced analytical tools for appropriate and efficient analysis of their microarray experiments and biostatisticians with insightful interpretation of Affymetrix microarray data.