High-dimensional Data Analysis Research Articles

Shared resource lab (SRL) strategies for supporting high-dimensional cytometry data analysis.

With the increase in the number of parameters that can be detected at the single-cell level using flow and mass cytometry, there has been a paradigm shift when handling and analyzing data sets. Cytometry Shared Resource Laboratories (SRLs) already take on the responsibility of ensuring users have resources and training in experimental design and operation of instruments to promote high-quality data acquisition. However, the role of SRLs downstream, during data handling and analysis, is not as well defined and agreed upon. Best practices dictate a central role for SRLs in this process as they are in a pivotal position to support research in this context, but key considerations about how to effectively fill this role need to be addressed. Two surveys and one workshop at CYTO 2022 in Philadelphia, PA, were performed to gain insight into what strategies SRLs are successfully employing to support high-dimensional data analysis and where SRLs and their users see limitations and long-term challenges in this area. Recommendations for high-dimensional data analysis support provided by SRLs will be offered and discussed.

Privacy-preserving and homogeneity-pursuit integrative analysis for high-dimensional censored data

Privacy-preserving and homogeneity-pursuit integrative analysis for high-dimensional censored data

Joint semiparametric kernel network regression.

Variable selection and graphical modeling play essential roles in highly correlated and high-dimensional (HCHD) data analysis. Variable selection methods have been developed under both parametric and nonparametric model settings. However, variable selection for nonadditive, nonparametric regression with high-dimensional variables is challenging due to complications in modeling unknown dependence structures among HCHD variables. Gaussian graphical models are a popular and useful tool for investigating the conditional dependence between variables via estimating sparse precision matrices. For a given class of interest, the estimated precision matrices can be mapped onto networks for visualization. However, the limitation of Gaussian graphical models is that they are only applicable to discretized response variables and for the case when , where is the number of variables and is the sample size. They are necessary to develop a joint method for variable selection and graphical modeling. To the best of our knowledge, the methods for simultaneously selecting variable selection and estimating networks among variables in the semiparametric regression settings are quite limited. Hence, in this paper, we develop a joint semiparametric kernel network regression method to solve this limitation and to provide a connection between them. Our approach is a unified and integrated method that can simultaneously identify important variables and build a network among those variables. We developed our approach under a semiparametric kernel machine regression framework, which can allow for nonlinear or nonadditive associations and complicated interactions among the variables. The advantages of our approach are that it can (1) simultaneously select variables and build a network among HCHD variables under a regression setting; (2) model unknown and complicated interactions among the variables and estimate the network among these variables; (3) allow for any form of semiparametric model, including non-additive, nonparametric model; and (4) provide an interpretable network that considers important variables and a response variable. We demonstrate our approach using a simulation study and real application on genetic pathway-based analysis.

CRUSTY: a versatile web platform for the rapid analysis and visualization of high-dimensional flow cytometry data

Flow cytometry (FCM) can investigate dozens of parameters from millions of cells and hundreds of specimens in a short time and at a reasonable cost, but the amount of data that is generated is considerable. Computational approaches are useful to identify novel subpopulations and molecular biomarkers, but generally require deep expertize in bioinformatics and the use of different platforms. To overcome these limitations, we introduce CRUSTY, an interactive, user-friendly webtool incorporating the most popular algorithms for FCM data analysis, and capable of visualizing graphical and tabular results and automatically generating publication-quality figures within minutes. CRUSTY also hosts an interactive interface for the exploration of results in real time. Thus, CRUSTY enables a large number of users to mine complex datasets and reduce the time required for data exploration and interpretation. CRUSTY is accessible at https://crusty.humanitas.it/.

High-Dimensional Data Global Sensitivity Analysis Based on Deep Soft Sensor Model.

This article investigates the sensitivity analysis (SA) of high-dimensional data to identify the effects of process variables on output quantity of interest (QoI) in industrial soft sensor modeling. The computational cost of analyzing the SA of high-dimensional data is high, and models available for SA techniques usually have limited generalization capacity. Therefore, we propose a novel high-dimensional data global SA (GSA) approach based on a deep soft sensor model to address these issues. We first develop an approximately incremental grouping (AIG) algorithm and a region-based cooperative co-evolution (RBCC) algorithm to decompose the high-dimensional data into independent regions for the GSA. Subsequently, a multihead deep soft sensor model with generalization performance is designed to determine the GSA indices of each decomposed region. Specifically, the region of interest (RoI) align algorithm provides the multihead with precisely located decomposed region features. Finally, based on the uncertainty analysis of each model head, we present a joint loss function with the Monte Carlo dropout (MC-dropout) algorithm to measure the GSA indices of each decomposed region on QoIs. Experimental evaluation results on a benchmark dataset and a real-world one demonstrate the effectiveness of the proposed approach in addressing the GSA of high-dimensional data in industrial processes.

THE SCALABLE BIRTH-DEATH MCMC ALGORITHM FOR MIXED GRAPHICAL MODEL LEARNING WITH APPLICATION TO GENOMIC DATA INTEGRATION.

Recent advances in biological research have seen the emergence of high-throughput technologies with numerous applications that allow the study of biological mechanisms at an unprecedented depth and scale. A large amount of genomic data is now distributed through consortia like The Cancer Genome Atlas (TCGA), where specific types of biological information on specific type of tissue or cell are available. In cancer research, the challenge is now to perform integrative analyses of high-dimensional multi-omic data with the goal to better understand genomic processes that correlate with cancer outcomes, e.g. elucidate gene networks that discriminate a specific cancer subgroups (cancer sub-typing) or discovering gene networks that overlap across different cancer types (pan-cancer studies). In this paper, we propose a novel mixed graphical model approach to analyze multi-omic data of different types (continuous, discrete and count) and perform model selection by extending the Birth-Death MCMC (BDMCMC) algorithm initially proposed by Stephens (2000) and later developed by Mohammadi and Wit (2015). We compare the performance of our method to the LASSO method and the standard BDMCMC method using simulations and find that our method is superior in terms of both computational efficiency and the accuracy of the model selection results. Finally, an application to the TCGA breast cancer data shows that integrating genomic information at different levels (mutation and expression data) leads to better subtyping of breast cancers.

Multiview Regularized Discriminant Canonical Correlation Analysis: Sequential Extraction of Relevant Features From Multiblock Data.

One of the important issues associated with real-life high-dimensional data analysis is how to extract significant and relevant features from multiview data. The multiset canonical correlation analysis (MCCA) is a well-known statistical method for multiview data integration. It finds a linear subspace that maximizes the correlations among different views. However, the existing methods to find the multiset canonical variables are computationally very expensive, which restricts the application of the MCCA in real-life big data analysis. The covariance matrix of each high-dimensional view may also suffer from the singularity problem due to the limited number of samples. Moreover, the MCCA-based existing feature extraction algorithms are, in general, unsupervised in nature. In this regard, a new supervised feature extraction algorithm is proposed, which integrates multimodal multidimensional data sets by solving maximal correlation problem of the MCCA. A new block matrix representation is introduced to reduce the computational complexity for computing the canonical variables of the MCCA. The analytical formulation enables efficient computation of the multiset canonical variables under supervised ridge regression optimization technique. It deals with the "curse of dimensionality" problem associated with high-dimensional data and facilitates the sequential generation of relevant features with significantly lower computational cost. The effectiveness of the proposed multiblock data integration algorithm, along with a comparison with other existing methods, is demonstrated on several benchmark and real-life cancer data.

Demystifying Statistics and Machine Learning in Analysis of Structured Tabular Data

Electronic health records have facilitated the extraction and analysis of a vast amount of data with many variables for clinical care and research. Conventional regression-based statistical methods may not capture all the complexities in high-dimensional data analysis. Therefore, researchers are increasingly using machine learning (ML)-based methods to better handle these more challenging datasets for the discovery of hidden patterns in patients’ data and for classification and predictive purposes. This article describes commonly used ML methods in structured data analysis with examples in orthopedic surgery. We present practical considerations in starting an ML project and appraising published studies in this field.

Shrinkage estimation for square of location parameter of the exponential distribution with known coefficient of variation

Shrinkage estimation has become a basic tool in the computational analysis of high-dimensional data. Historically and conceptually a key development toward this was the discovery of the inadmissibility of the usual estimator of a multivariate normal mean. This study explores the problem of estimating the square of location parameter of an exponential distribution when the coefficient of variation is known without error. Several estimators have been proposed with their properties. The best unbiased estimator as well least minimum mean square error (MMSE) estimator has been identified among several estimators. Numerical illustrations are given in the support of the present study.

Deep Direct Discriminative Decoders for High-dimensional Time-series Data Analysis

The state-space models (SSMs) are widely utilized in the analysis of time-series data. SSMs rely on an explicit definition of the state and observation processes. Characterizing these processes is not always easy and becomes a modeling challenge when the dimension of observed data grows or the observed data distribution deviates from the normal distribution. Here, we propose a new formulation of SSM for high-dimensional observation processes with a heavy-tailed distribution. We call this solution the deep direct discriminative process (D4). The D4 brings deep neural networks’ expressiveness and scalability to the SSM formulation letting us build a novel solution that efficiently estimates the underlying state processes through high-dimensional observation signal.We demonstrate the D4 solutions in simulated and real data such as Lorenz attractors, Langevin dynamics, random walk dynamics, and rat hippocampus spiking neural data and show that the D4’s performance precedes traditional SSMs and RNNs. The D4 can be applied to a broader class of time-series data where the connection between high-dimensional observation and the underlying latent process is hard to characterize.

Single-cell multi-omics topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures

The advent of single-cell multi-omics sequencing technology makes it possible for researchers to leverage multiple modalities for individual cells and explore cell heterogeneity. However, the high-dimensional, discrete, and sparse nature of the data make the downstream analysis particularly challenging. Here, we propose an interpretable deep learning method called moETM to perform integrative analysis of high-dimensional single-cell multimodal data. moETM integrates multiple omics data via a product-of-experts in the encoder and employs multiple linear decoders to learn the multi-omics signatures. moETM demonstrates superior performance compared with six state-of-the-art methods on seven publicly available datasets. By applying moETM to the scRNA+ scATAC data, we identified sequence motifs corresponding to the transcription factors regulating immune gene signatures. Applying moETM to CITE-seq data from the COVID-19 patients revealed not only known immune cell-type-specific signatures but also composite multi-omics biomarkers of critical conditions due to COVID-19, thus providing insights from both biological and clinical perspectives.

Maternal Exposure to Trace Elements, Toxic Metals, and Longitudinal Changes in Infancy Anthropometry and Growth Trajectories: A Prospective Cohort Study.

Exploration of stage-specific effects of maternal exposure to trace elements and toxic metals on infancy continuous growth and trajectories is critical for early-life health management. Within a Chinese prospective cohort in 2014-2015, a total of 919 mother-infant pairs were included, and the urinary levels of 17 elements including vanadium (V), chromium (Cr), manganese, iron, cobalt, nickel, copper, zinc, arsenic, molybdenum, palladium, cadmium, tin, gold, mercury, thallium, and lead in early (mean: 11.9 weeks), and late pregnancy (mean: 32.4 weeks) were assessed. Standardized anthropometric assessments of infants were conducted at 1, 3, 6, 8, and 12 months of age. A three-step longitudinal and high-dimensional data analysis procedure was carried out to estimate the impacts of exposome on dynamic growth. Early-pregnancy exposures to V and Cr were positively associated with repeated measurements of length-for-age z-scores (LAZ). Six trajectories were identified based on LAZ. Maternal single exposure to V and Cr as well as mixed exposure to trace elements in early pregnancy were associated with raised odds for the high-stable group. Our results suggested positive associations between maternal trace element exposome and infancy dynamic growth. V and Cr were the key elements and the early pregnancy might be the critical window.

Exploitation of surrogate variables in random forests for unbiased analysis of mutual impact and importance of features.

Random forest is a popular machine learning approach for the analysis of high-dimensional data because it is flexible and provides variable importance measures for the selection of relevant features. However, the complex relationships between the features are usually not considered for the selection and thus also neglected for the characterization of the analysed samples. Here we propose two novel approaches that focus on the mutual impact of features in random forests. Mutual forest impact (MFI) is a relation parameter that evaluates the mutual association of the features to the outcome and, hence, goes beyond the analysis of correlation coefficients. Mutual impurity reduction (MIR) is an importance measure that combines this relation parameter with the importance of the individual features. MIR and MFI are implemented together with testing procedures that generate P-values for the selection of related and important features. Applications to one experimental and various simulated datasets and the comparison to other methods for feature selection and relation analysis show that MFI and MIR are very promising to shed light on the complex relationships between features and outcome. In addition, they are not affected by common biases, e.g. that features with many possible splits or high minor allele frequencies are preferred. The approaches are implemented in Version 0.3.3 of the R package RFSurrogates that is available at github.com/AGSeifert/RFSurrogates and the data are available at doi.org/10.25592/uhhfdm.12620.

Fast optimization methods for high-dimensional row-sparse multivariate quantile linear regression

Sparse quantile regression is a useful tool for variable selection, robust estimation and heteroscedasticity treatment in high-dimensional data analysis. Due to the non-smooth of quantile loss, the computation is heavier than the least square models. In the literature, there are various numerical methods for linear quantile regression, such as ADMM developed in Gu et al. [Technometrics. 2017;60(3):319–331]. However, the computation of multivariate quantile regression has not yet been fully resolved, especially when the dimension is high. Motivated by this, we will focus on the design of fast numerical algorithms for row-sparse multivariate quantile regression model. By virtue of proximal operator and Majorize–Minimization, four smoothed algorithms are designed. For all the obtained algorithms, we analyse their convergence and the parameter selection. We conduct plenty of simulations and four real data sets analysis. Finally, we conclude that the smoothed method is faster than the non-smooth method, especially when the number of predictors is large.

High-Dimensional Feature Selection Based on Improved Binary Ant Colony Optimization Combined with Hybrid Rice Optimization Algorithm

In the realm of high-dimensional data analysis, numerous fields stand to benefit from its applications, including the biological and medical sectors that are crucial for computer-aided disease diagnosis and prediction systems. However, the presence of a significant number of redundant or irrelevant features can adversely affect system accuracy and real-time diagnosis efficiency. To mitigate this issue, this paper proposes two innovative wrapper feature selection (FS) methods that integrate the ant colony optimization (ACO) algorithm and hybrid rice optimization (HRO). HRO is a recently developed metaheuristic that mimics the breeding process of the three-line hybrid rice, which is yet to be thoroughly explored in the context of solving high-dimensional FS problems. In the first hybridization, ACO is embedded as an evolutionary operator within HRO and updated alternately with it. In the second form of hybridization, two subpopulations evolve independently, sharing the local search results to assist individual updating. In the initial stage preceding hybridization, a problem-oriented heuristic factor assignment strategy based on the importance of the knee point feature is introduced to enhance the global search capability of ACO in identifying the smallest and most representative features. The performance of the proposed algorithms is evaluated on fourteen high-dimensional biomedical datasets and compared with other recently advanced FS methods. Experimental results suggest that the proposed methods are efficient and computationally robust, exhibiting superior performance compared to the other algorithms involved in this study.

Analysis of high-dimensional metabolomics data with complex temporal dynamics using RM-ASCA.

The intricate dependency structure of biological "omics" data, particularly those originating from longitudinal intervention studies with frequently sampled repeated measurements renders the analysis of such data challenging. The high-dimensionality, inter-relatedness of multiple outcomes, and heterogeneity in the studied systems all add to the difficulty in deriving meaningful information. In addition, the subtle differences in dynamics often deemed meaningful in nutritional intervention studies can be particularly challenging to quantify. In this work we demonstrate the use of quantitative longitudinal models within the repeated-measures ANOVA simultaneous component analysis+ (RM-ASCA+) framework to capture the dynamics in frequently sampled longitudinal data with multivariate outcomes. We illustrate the use of linear mixed models with polynomial and spline basis expansion of the time variable within RM-ASCA+ in order to quantify non-linear dynamics in a simulation study as well as in a metabolomics data set. We show that the proposed approach presents a convenient and interpretable way to systematically quantify and summarize multivariate outcomes in longitudinal studies while accounting for proper within subject dependency structures.

Unsupervised classification applications in enhancing lithological mapping and geological understanding: a case study from Northern Ireland

Pattern classification algorithms can help us to recognize and predict patterns in large and complex multivariate datasets. Self-organizing maps (SOMs), which use competitive learning, are unsupervised classification tools that are considered to be very useful in pattern classification and recognition. This technique is based on the principles of vector quantification of similarities and clustering in a high-dimensional space and the method can handle the analysis and visualization of high-dimensional data. This tool is ideal for analysing a complex combination of categorical and continuous spatial variables, with particular applications to geological features. We used SOMs to predict geological features based on airborne geophysical data acquired through the Tellus Project in Northern Ireland. The SOMs were applied through 20 experiments (iterations), incorporating radiometric data in combination with geological features, including elevation, slope angle, terrain ruggedness and geochronology. The SOMs were able to differentiate contrasting bedrock geology, such as acidic v. mafic igneous rocks, although data clustering over intermediate rocks was less clear. The presence of a thick cover of glacial deposits in most of the study area presented a challenge for data clustering, particularly over the intermediate igneous and sedimentary bedrock types. Supplementary material: Twenty iterations were carried out during this research. Only six are included in the article. The rest of the iterations are available at https://doi.org/10.6084/m9.figshare.c.6603098

Hedging Covid-19 risk with ESG disclosure

Covid-19 has led to major changes worldwide and has had a significant impact on market risk. We characterize this uncertainty as innovations extracted from the Covid Risk Index on the Wall Street Journal through a textual analysis of high-dimensional data. We hedge the risk with mimicking portfolios constructed using the ESG (environmental, social, and governance) disclosure score as a measure of firm-level exposure to Covid-19 risk. The hedge portfolios perform well both in and out of sample. We also test the role of ESG in hedging and discover that during the Covid-19 pandemic firms with greater ESG disclosure generate higher returns as well as experience lower downside risk. The further analysis suggests that the portfolio returns can be explained by Covid risk shock and investment inflow, and the hedge effect mainly comes from the social part of ESG.

Prediction approaches for partly missing multi‐omics covariate data: A literature review and an empirical comparison study

AbstractAs the availability of omics data has increased in the last few years, more multi‐omics data have been generated, that is, high‐dimensional molecular data consisting of several types such as genomic, transcriptomic, or proteomic data, all obtained from the same patients. Such data lend themselves to being used as covariates in automatic outcome prediction because each omics type may contribute unique information, possibly improving predictions compared to using only one omics data type. Frequently, however, in the training data and the data to which automatic prediction rules should be applied, the test data, the different omics data types are not available for all patients. We refer to this type of data as block‐wise missing multi‐omics data. First, we provide a literature review on existing prediction methods applicable to such data. Subsequently, using a collection of 13 publicly available multi‐omics data sets, we compare the predictive performances of several of these approaches for different block‐wise missingness patterns. Finally, we discuss the results of this empirical comparison study and draw some tentative conclusions.This article is categorized under: Applications of Computational Statistics > Genomics/Proteomics/Genetics Applications of Computational Statistics > Health and Medical Data/Informatics Statistical and Graphical Methods of Data Analysis > Analysis of High Dimensional Data

Statistical analysis of high-dimensional biomedical data: a gentle introduction to analytical goals, common approaches and challenges

BackgroundIn high-dimensional data (HDD) settings, the number of variables associated with each observation is very large. Prominent examples of HDD in biomedical research include omics data with a large number of variables such as many measurements across the genome, proteome, or metabolome, as well as electronic health records data that have large numbers of variables recorded for each patient. The statistical analysis of such data requires knowledge and experience, sometimes of complex methods adapted to the respective research questions.MethodsAdvances in statistical methodology and machine learning methods offer new opportunities for innovative analyses of HDD, but at the same time require a deeper understanding of some fundamental statistical concepts. Topic group TG9 “High-dimensional data” of the STRATOS (STRengthening Analytical Thinking for Observational Studies) initiative provides guidance for the analysis of observational studies, addressing particular statistical challenges and opportunities for the analysis of studies involving HDD. In this overview, we discuss key aspects of HDD analysis to provide a gentle introduction for non-statisticians and for classically trained statisticians with little experience specific to HDD.ResultsThe paper is organized with respect to subtopics that are most relevant for the analysis of HDD, in particular initial data analysis, exploratory data analysis, multiple testing, and prediction. For each subtopic, main analytical goals in HDD settings are outlined. For each of these goals, basic explanations for some commonly used analysis methods are provided. Situations are identified where traditional statistical methods cannot, or should not, be used in the HDD setting, or where adequate analytic tools are still lacking. Many key references are provided.ConclusionsThis review aims to provide a solid statistical foundation for researchers, including statisticians and non-statisticians, who are new to research with HDD or simply want to better evaluate and understand the results of HDD analyses.