scholarly journals IPF-LASSO: Integrative L1-Penalized Regression with Penalty Factors for Prediction Based on Multi-Omics Data

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Anne-Laure Boulesteix ◽  
Riccardo De Bin ◽  
Xiaoyu Jiang ◽  
Mathias Fuchs
Keyword(s):  
Cross Validation ◽  
Real Life ◽  
Penalized Regression ◽  
R Package ◽  
Molecular Data ◽  
Regression Method ◽  
Data Driven ◽  
High Dimensional ◽  
Omics Data ◽  
Simulation Studies

As modern biotechnologies advance, it has become increasingly frequent that different modalities of high-dimensional molecular data (termed “omics” data in this paper), such as gene expression, methylation, and copy number, are collected from the same patient cohort to predict the clinical outcome. While prediction based on omics data has been widely studied in the last fifteen years, little has been done in the statistical literature on the integration of multiple omics modalities to select a subset of variables for prediction, which is a critical task in personalized medicine. In this paper, we propose a simple penalized regression method to address this problem by assigning different penalty factors to different data modalities for feature selection and prediction. The penalty factors can be chosen in a fully data-driven fashion by cross-validation or by taking practical considerations into account. In simulation studies, we compare the prediction performance of our approach, called IPF-LASSO (Integrative LASSO with Penalty Factors) and implemented in the R package ipflasso, with the standard LASSO and sparse group LASSO. The use of IPF-LASSO is also illustrated through applications to two real-life cancer datasets. All data and codes are available on the companion website to ensure reproducibility.

scholarly journals An R Package for Divergence Analysis of Omics Data

2019 ◽  
Author(s):  
Wikum Dinalankara ◽  
Qian Ke ◽  
Donald Geman ◽  
Luigi Marchionni
Keyword(s):  
High Throughput Sequencing ◽  
R Package ◽  
The Cancer Genome Atlas ◽  
High Dimensional ◽  
Omics Data ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Ternary Code ◽  
Cancer Genome Atlas ◽  
Level Analysis

AbstractGiven the ever-increasing amount of high-dimensional and complex omics data becoming available, it is increasingly important to discover simple but effective methods of analysis. Divergence analysis transforms each entry of a high-dimensional omics profile into a digitized (binary or ternary) code based on the deviation of the entry from a given baseline population. This is a novel framework that is significantly different from existing omics data analysis methods: it allows digitization of continuous omics data at the univariate or multivariate level, facilitates sample level analysis, and is applicable on many different omics platforms. The divergence package, available on the R platform through the Bioconductor repository collection, provides easy-to-use functions for carrying out this transformation. Here we demonstrate how to use the package with sample high throughput sequencing data from the Cancer Genome Atlas.

scholarly journals An R package for divergence analysis of omics data

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249002
Author(s):  
Wikum Dinalankara ◽  
Qian Ke ◽  
Donald Geman ◽  
Luigi Marchionni
Keyword(s):  
R Package ◽  
The Cancer Genome Atlas ◽  
High Dimensional ◽  
Omics Data ◽  
Ternary Code ◽  
Cancer Genome Atlas ◽  
Level Analysis ◽  
Data Analysis Methods ◽  
Genome Atlas ◽  
Omics Data Analysis

Given the ever-increasing amount of high-dimensional and complex omics data becoming available, it is increasingly important to discover simple but effective methods of analysis. Divergence analysis transforms each entry of a high-dimensional omics profile into a digitized (binary or ternary) code based on the deviation of the entry from a given baseline population. This is a novel framework that is significantly different from existing omics data analysis methods: it allows digitization of continuous omics data at the univariate or multivariate level, facilitates sample level analysis, and is applicable on many different omics platforms. The divergence package, available on the R platform through the Bioconductor repository collection, provides easy-to-use functions for carrying out this transformation. Here we demonstrate how to use the package with data from the Cancer Genome Atlas.

scholarly journals Multi-kernel linear mixed model with adaptive lasso for prediction analysis on high-dimensional multi-omics data

2019 ◽  
Vol 36 (6) ◽  
pp. 1785-1794
Author(s):  
Jun Li ◽  
Qing Lu ◽  
Yalu Wen
Keyword(s):  
Risk Prediction ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
R Package ◽  
Kernel Functions ◽  
Adaptive Lasso ◽  
Supplementary Information ◽  
High Dimensional ◽  
Omics Data ◽  
Modeling Framework

Abstract Motivation The use of human genome discoveries and other established factors to build an accurate risk prediction model is an essential step toward precision medicine. While multi-layer high-dimensional omics data provide unprecedented data resources for prediction studies, their corresponding analytical methods are much less developed. Results We present a multi-kernel penalized linear mixed model with adaptive lasso (MKpLMM), a predictive modeling framework that extends the standard linear mixed models widely used in genomic risk prediction, for multi-omics data analysis. MKpLMM can capture not only the predictive effects from each layer of omics data but also their interactions via using multiple kernel functions. It adopts a data-driven approach to select predictive regions as well as predictive layers of omics data, and achieves robust selection performance. Through extensive simulation studies, the analyses of PET-imaging outcomes from the Alzheimer’s Disease Neuroimaging Initiative study, and the analyses of 64 drug responses, we demonstrate that MKpLMM consistently outperforms competing methods in phenotype prediction. Availability and implementation The R-package is available at https://github.com/YaluWen/OmicPred. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals An Efficient Algorithm for the Detection of Outliers in Mislabeled Omics Data

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hongwei Sun ◽  
Jiu Wang ◽  
Zhongwen Zhang ◽  
Naibao Hu ◽  
Tong Wang
Keyword(s):  
Computation Time ◽  
Likelihood Estimation ◽  
Penalized Regression ◽  
High Dimensional ◽  
Omics Data ◽  
Rna Seq ◽  
Criterion Function ◽  
Average Computation Time ◽  
Concentration Step ◽  
Step Algorithm

High dimensionality and noise have made it difficult to detect related biomarkers in omics data. Through previous study, penalized maximum trimmed likelihood estimation is effective in identifying mislabeled samples in high-dimensional data with mislabeled error. However, the algorithm commonly used in these studies is the concentration step (C-step), and the C-step algorithm that is applied to robust penalized regression does not ensure that the criterion function is gradually optimized iteratively, because the regularized parameters change during the iteration. This makes the C-step algorithm runs very slowly, especially when dealing with high-dimensional omics data. The AR-Cstep (C-step combined with an acceptance-rejection scheme) algorithm is proposed. In simulation experiments, the AR-Cstep algorithm converged faster (the average computation time was only 2% of that of the C-step algorithm) and was more accurate in terms of variable selection and outlier identification than the C-step algorithm. The two algorithms were further compared on triple negative breast cancer (TNBC) RNA-seq data. AR-Cstep can solve the problem of the C-step not converging and ensures that the iterative process is in the direction that improves criterion function. As an improvement of the C-step algorithm, the AR-Cstep algorithm can be extended to other robust models with regularized parameters.

scholarly journals A robust variable screening procedure for ultra-high dimensional data

2021 ◽  
pp. 096228022110172
Author(s):  
Abhik Ghosh ◽  
Magne Thoresen
Keyword(s):  
Penalized Regression ◽  
Screening Procedure ◽  
Small Samples ◽  
High Dimensional ◽  
Simulation Studies ◽  
Robust Methods ◽  
Density Power Divergence ◽  
Variable Screening ◽  
Regression Problems ◽  
Power Divergence

Variable selection in ultra-high dimensional regression problems has become an important issue. In such situations, penalized regression models may face computational problems and some pre-screening of the variables may be necessary. A number of procedures for such pre-screening has been developed; among them the Sure Independence Screening (SIS) enjoys some popularity. However, SIS is vulnerable to outliers in the data, and in particular in small samples this may lead to faulty inference. In this paper, we develop a new robust screening procedure. We build on the density power divergence (DPD) estimation approach and introduce DPD-SIS and its extension iterative DPD-SIS. We illustrate the behavior of the methods through extensive simulation studies and show that they are superior to both the original SIS and other robust methods when there are outliers in the data. Finally, we illustrate its use in a study on regulation of lipid metabolism.

scholarly journals A Sparse Additive Model for High-Dimensional Interactions with an Exposure Variable

2018 ◽  
Author(s):  
Sahir R Bhatnagar ◽  
Tianyuan Lu ◽  
Amanda Lovato ◽  
David L Olds ◽  
Michael S Kobor ◽  
...  
Keyword(s):  
Biological Networks ◽  
Intervention Program ◽  
Additive Model ◽  
Penalized Regression ◽  
R Package ◽  
Tuning Parameter ◽  
High Dimensional ◽  
Non Linear ◽  
Exposure Variable ◽  
Linear Interactions

AbstractA conceptual paradigm for onset of a new disease is often considered to be the result of changes in entire biological networks whose states are affected by a complex interaction of genetic and environmental factors. However, when modelling a relevant phenotype as a function of high dimensional measurements, power to estimate inter-actions is low, the number of possible interactions could be enormous and their effects may be non-linear. Existing approaches for high dimensional modelling such as the lasso might keep an interaction but remove a main effect, which is problematic for interpretation. In this work, we introduce a method called sail for detecting non-linear interactions with a key environmental or exposure variable in high-dimensional settings which respects either the strong or weak heredity constraints. We prove that asymptotically, our method possesses the oracle property, i.e., it performs as well as if the true model were known in advance. We develop a computationally effcient fitting algorithm with automatic tuning parameter selection, which scales to high-dimensional datasets. Through an extensive simulation study, we show that sail out-performs existing penalized regression methods in terms of prediction accuracy and support recovery when there are non-linear interactions with an exposure variable. We then apply sail to detect non-linear interactions between genes and a prenatal psychosocial intervention program on cognitive performance in children at 4 years of age. Results from our method show that individuals who are genetically predisposed to lower educational attainment are those who stand to benefit the most from the intervention. Our algorithms are implemented in an R package available on CRAN (https://cran.r-project.org/package=sail).

scholarly journals Robust logistic zero-sum regression for microbiome compositional data

2021 ◽  
Author(s):  
G. S. Monti ◽  
P. Filzmoser
Keyword(s):  
Compositional Data ◽  
R Package ◽  
High Dimensional ◽  
Simulation Studies ◽  
Contrast Model ◽  
Sparse Logistic Regression ◽  
Regression Estimators ◽  
The Stability ◽  
Zero Sum ◽  
Microbiome Data

AbstractWe introduce the Robust Logistic Zero-Sum Regression (RobLZS) estimator, which can be used for a two-class problem with high-dimensional compositional covariates. Since the log-contrast model is employed, the estimator is able to do feature selection among the compositional parts. The proposed method attains robustness by minimizing a trimmed sum of deviances. A comparison of the performance of the RobLZS estimator with a non-robust counterpart and with other sparse logistic regression estimators is conducted via Monte Carlo simulation studies. Two microbiome data applications are considered to investigate the stability of the estimators to the presence of outliers. Robust Logistic Zero-Sum Regression is available as an R package that can be downloaded at https://github.com/giannamonti/RobZS.

scholarly journals Adaptive penalization in high-dimensional regression and classification with external covariates using variational Bayes

Biostatistics ◽  
2019 ◽  
Author(s):  
Britta Velten ◽  
Wolfgang Huber
Keyword(s):  
Dynamic Range ◽  
Penalized Regression ◽  
Relative Strength ◽  
Prediction Performance ◽  
Data Driven ◽  
Effect Sizes ◽  
High Dimensional ◽  
Optimization Scheme ◽  
Additional Information ◽  
Tool Set

Summary Penalization schemes like Lasso or ridge regression are routinely used to regress a response of interest on a high-dimensional set of potential predictors. Despite being decisive, the question of the relative strength of penalization is often glossed over and only implicitly determined by the scale of individual predictors. At the same time, additional information on the predictors is available in many applications but left unused. Here, we propose to make use of such external covariates to adapt the penalization in a data-driven manner. We present a method that differentially penalizes feature groups defined by the covariates and adapts the relative strength of penalization to the information content of each group. Using techniques from the Bayesian tool-set our procedure combines shrinkage with feature selection and provides a scalable optimization scheme. We demonstrate in simulations that the method accurately recovers the true effect sizes and sparsity patterns per feature group. Furthermore, it leads to an improved prediction performance in situations where the groups have strong differences in dynamic range. In applications to data from high-throughput biology, the method enables re-weighting the importance of feature groups from different assays. Overall, using available covariates extends the range of applications of penalized regression, improves model interpretability and can improve prediction performance.

EpiPen: An R Package to Investigate Two-Locus Epistatic Models

2014 ◽  
Vol 17 (4) ◽  
Author(s):  
Raymond K. Walters ◽  
Charles Laurin ◽  
Gitta H. Lubke
Keyword(s):  
Power Analysis ◽  
R Package ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Epistatic Interactions ◽  
Model Interpretation ◽  
Genome Wide ◽  
Using Data ◽  
Power Analyses

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, EpiPen, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. EpiPen facilitates research on SNP-SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

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