Computationally scalable regression modeling for ultrahigh-dimensional omics data with ParProx.
Ontology highlight
ABSTRACT:
SUBMITTER: Ko S
PROVIDER: S-EPMC8575036 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The UK Biobank is a very large, prospective population-based cohort study across the United Kingdom. It provides unprecedented opportunities for researchers to investigate the relationship between genotypic information and phenotypes of interest. Multiple regression methods, compared with genome-wide association studies (GWAS), have already been showed to greatly improve the prediction performance for a variety of phenotypes. In the high-dimensional settings, the lasso, since its first proposal in statistics, has been proved to be an effective method for simultaneous variable selection and estimation. However, the large-scale and ultrahigh dimension seen in the UK Biobank pose new challenges for applying the lasso method, as many existing algorithms and their implementations are not scalable to large applications. In this paper, we propose a computational framework called batch screening iterative lasso (BASIL) that can take advantage of any existing lasso solver and easily build a scalable solution for very large data, including those that are larger than the memory size. We introduce snpnet, an R package that implements the proposed algorithm on top of glmnet and optimizes for single nucleotide polymorphism (SNP) datasets. It currently supports ℓ1-penalized linear model, logistic regression, Cox model, and also extends to the elastic net with ℓ1/ℓ2 penalty. We demonstrate results on the UK Biobank dataset, where we achieve competitive predictive performance for all four phenotypes considered (height, body mass index, asthma, high cholesterol) using only a small fraction of the variants compared with other established polygenic risk score methods.
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Project description:Bayesian model selection procedures based on nonlocal alternative prior densities are extended to ultrahigh dimensional settings and compared to other variable selection procedures using precision-recall curves. Variable selection procedures included in these comparisons include methods based on g-priors, reciprocal lasso, adaptive lasso, scad, and minimax concave penalty criteria. The use of precision-recall curves eliminates the sensitivity of our conclusions to the choice of tuning parameters. We find that Bayesian variable selection procedures based on nonlocal priors are competitive to all other procedures in a range of simulation scenarios, and we subsequently explain this favorable performance through a theoretical examination of their consistency properties. When certain regularity conditions apply, we demonstrate that the nonlocal procedures are consistent for linear models even when the number of covariates p increases sub-exponentially with the sample size n. A model selection procedure based on Zellner's g-prior is also found to be competitive with penalized likelihood methods in identifying the true model, but the posterior distribution on the model space induced by this method is much more dispersed than the posterior distribution induced on the model space by the nonlocal prior methods. We investigate the asymptotic form of the marginal likelihood based on the nonlocal priors and show that it attains a unique term that cannot be derived from the other Bayesian model selection procedures. We also propose a scalable and efficient algorithm called Simplified Shotgun Stochastic Search with Screening (S5) to explore the enormous model space, and we show that S5 dramatically reduces the computing time without losing the capacity to search the interesting region in the model space, at least in the simulation settings considered. The S5 algorithm is available in an R package BayesS5 on CRAN.
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Project description:Maturing omics technologies enable researchers to generate high dimension omics data (HDOD) routinely in translational clinical studies. In the field of oncology, The Cancer Genome Atlas (TCGA) provided funding support to researchers to generate different types of omics data on a common set of biospecimens with accompanying clinical data and has made the data available for the research community to mine. One important application, and the focus of this manuscript, is to build predictive models for prognostic outcomes based on HDOD. To complement prevailing regression-based approaches, we propose to use an object-oriented regression (OOR) methodology to identify exemplars specified by HDOD patterns and to assess their associations with prognostic outcome. Through computing patient's similarities to these exemplars, the OOR-based predictive model produces a risk estimate using a patient's HDOD. The primary advantages of OOR are twofold: reducing the penalty of high dimensionality and retaining the interpretability to clinical practitioners. To illustrate its utility, we apply OOR to gene expression data from non-small cell lung cancer patients in TCGA and build a predictive model for prognostic survivorship among stage I patients, i.e., we stratify these patients by their prognostic survival risks beyond histological classifications. Identification of these high-risk patients helps oncologists to develop effective treatment protocols and post-treatment disease management plans. Using the TCGA data, the total sample is divided into training and validation data sets. After building up a predictive model in the training set, we compute risk scores from the predictive model, and validate associations of risk scores with prognostic outcome in the validation data (P-value=0.015).
| S-EPMC5097461 | biostudies-literature
Project description:BACKGROUND:Recent technological developments have enabled the measurement of a plethora of biomolecular data from various omics domains, and research is ongoing on statistical methods to leverage these omics data to better model and understand biological pathways and genetic architectures of complex phenotypes. Current reviews report that the simultaneous analysis of multiple (i.e. three or more) high dimensional omics data sources is still challenging and suitable statistical methods are unavailable. Often mentioned challenges are the lack of accounting for the hierarchical structure between omics domains and the difficulty of interpretation of genomewide results. This study is motivated to address these challenges. We propose multiset sparse Partial Least Squares path modeling (msPLS), a generalized penalized form of Partial Least Squares path modeling, for the simultaneous modeling of biological pathways across multiple omics domains. msPLS simultaneously models the effect of multiple molecular markers, from multiple omics domains, on the variation of multiple phenotypic variables, while accounting for the relationships between data sources, and provides sparse results. The sparsity in the model helps to provide interpretable results from analyses of hundreds of thousands of biomolecular variables. RESULTS:With simulation studies, we quantified the ability of msPLS to discover associated variables among high dimensional data sources. Furthermore, we analysed high dimensional omics datasets to explore biological pathways associated with Marfan syndrome and with Chronic Lymphocytic Leukaemia. Additionally, we compared the results of msPLS to the results of Multi-Omics Factor Analysis (MOFA), which is an alternative method to analyse this type of data. CONCLUSIONS:msPLS is an multiset multivariate method for the integrative analysis of multiple high dimensional omics data sources. It accounts for the relationship between multiple high dimensional data sources while it provides interpretable results through its sparse solutions. The biomarkers found by msPLS in the omics datasets can be interpreted in terms of biological pathways associated with the pathophysiology of Marfan syndrome and of Chronic Lymphocytic Leukaemia. Additionally, msPLS outperforms MOFA in terms of variation explained in the chronic lymphocytic leukaemia dataset while it identifies the two most important clinical markers for Chronic Lymphocytic Leukaemia AVAILABILITY: http://uva.csala.me/mspls.https://github.com/acsala/2018_msPLS.
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Project description:BACKGROUND:The problem of assessing associations between multiple omics data including genomics and metabolomics data to identify biomarkers potentially predictive of complex diseases has garnered considerable research interest nowadays. A popular epidemiology approach is to consider an association of each of the predictors with each of the response using a univariate linear regression model, and to select predictors that meet a priori specified significance level. Although this approach is simple and intuitive, it tends to require larger sample size which is costly. It also assumes variables for each data type are independent, and thus ignores correlations that exist between variables both within each data type and across the data types. RESULTS:We consider a multivariate linear regression model that relates multiple predictors with multiple responses, and to identify multiple relevant predictors that are simultaneously associated with the responses. We assume the coefficient matrix of the responses on the predictors is both row-sparse and of low-rank, and propose a group Dantzig type formulation to estimate the coefficient matrix. CONCLUSION:Extensive simulations demonstrate the competitive performance of our proposed method when compared to existing methods in terms of estimation, prediction, and variable selection. We use the proposed method to integrate genomics and metabolomics data to identify genetic variants that are potentially predictive of atherosclerosis cardiovascular disease (ASCVD) beyond well-established risk factors. Our analysis shows some genetic variants that increase prediction of ASCVD beyond some well-established factors of ASCVD, and also suggest a potential utility of the identified genetic variants in explaining possible association between certain metabolites and ASCVD.
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Project description:The ongoing global change and the increased interest in macroecological processes call for the analysis of spatially extensive data on species communities to understand and forecast distributional changes of biodiversity. Recently developed joint species distribution models can deal with numerous species efficiently, while explicitly accounting for spatial structure in the data. However, their applicability is generally limited to relatively small spatial data sets because of their severe computational scaling as the number of spatial locations increases. In this work, we propose a practical alleviation of this scalability constraint for joint species modeling by exploiting two spatial-statistics techniques that facilitate the analysis of large spatial data sets: Gaussian predictive process and nearest-neighbor Gaussian process. We devised an efficient Gibbs posterior sampling algorithm for Bayesian model fitting that allows us to analyze community data sets consisting of hundreds of species sampled from up to hundreds of thousands of spatial units. The performance of these methods is demonstrated using an extensive plant data set of 30,955 spatial units as a case study. We provide an implementation of the presented methods as an extension to the hierarchical modeling of species communities framework.
| S-EPMC7027487 | biostudies-literature
Project description:Variable selection for structured covariates lying on an underlying known graph is a problem motivated by practical applications, and has been a topic of increasing interest. However, most of the existing methods may not be scalable to high-dimensional settings involving tens of thousands of variables lying on known pathways such as the case in genomics studies. We propose an adaptive Bayesian shrinkage approach which incorporates prior network information by smoothing the shrinkage parameters for connected variables in the graph, so that the corresponding coefficients have a similar degree of shrinkage. We fit our model via a computationally efficient expectation maximization algorithm which scalable to high-dimensional settings ( p ? 100 , 000 ). Theoretical properties for fixed as well as increasing dimensions are established, even when the number of variables increases faster than the sample size. We demonstrate the advantages of our approach in terms of variable selection, prediction, and computational scalability via a simulation study, and apply the method to a cancer genomics study.
| S-EPMC6222001 | biostudies-literature
Project description:Feature screening plays an important role in dimension reduction for ultrahigh-dimensional data. In this paper, we introduce a new feature screening method and establish its sure independence screening property under the ultrahigh-dimensional setting. The proposed method works based on the nonparanormal transformation and Henze-Zirkler's test; that is, it first transforms the response variable and features to Gaussian random variables using the nonparanormal transformation and then tests the dependence between the response variable and features using the Henze-Zirkler's test. The proposed method enjoys at least two merits. First, it is model-free, which avoids the specification of a particular model structure. Second, it is condition-free, which does not require any extra conditions except for some regularity conditions for high-dimensional feature screening. The numerical results indicate that, compared to the existing methods, the proposed method is more robust to the data generated from heavy-tailed distributions and/or complex models with interaction variables. The proposed method is applied to screening of anticancer drug response genes.
| S-EPMC6284821 | biostudies-literature
Project description:Inferring cellular trajectories using a variety of omic data is a critical task in single-cell data science. However, accurate prediction of cell fates, and thereby biologically meaningful discovery, is challenged by the sheer size of single-cell data, the diversity of omic data types, and the complexity of their topologies. We present VIA, a scalable trajectory inference algorithm that overcomes these limitations by using lazy-teleporting random walks to accurately reconstruct complex cellular trajectories beyond tree-like pathways (e.g., cyclic or disconnected structures). We show that VIA robustly and efficiently unravels the fine-grained sub-trajectories in a 1.3-million-cell transcriptomic mouse atlas without losing the global connectivity at such a high cell count. We further apply VIA to discovering elusive lineages and less populous cell fates missed by other methods across a variety of data types, including single-cell proteomic, epigenomic, multi-omics datasets, and a new in-house single-cell morphological dataset.
| S-EPMC8452770 | biostudies-literature
Project description:BackgroundData anonymization is an important building block for ensuring privacy and fosters the reuse of data. However, transforming the data in a way that preserves the privacy of subjects while maintaining a high degree of data quality is challenging and particularly difficult when processing complex datasets that contain a high number of attributes. In this article we present how we extended the open source software ARX to improve its support for high-dimensional, biomedical datasets.FindingsFor improving ARX's capability to find optimal transformations when processing high-dimensional data, we implement 2 novel search algorithms. The first is a greedy top-down approach and is oriented on a formally implemented bottom-up search. The second is based on a genetic algorithm. We evaluated the algorithms with different datasets, transformation methods, and privacy models. The novel algorithms mostly outperformed the previously implemented bottom-up search. In addition, we extended the GUI to provide a high degree of usability and performance when working with high-dimensional datasets.ConclusionWith our additions we have significantly enhanced ARX's ability to handle high-dimensional data in terms of processing performance as well as usability and thus can further facilitate data sharing.
| S-EPMC8489190 | biostudies-literature