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Feature Selection for Longitudinal Data by Using Sign Averages to Summarize Gene Expression Values over Time.

ABSTRACT: With the rapid evolution of high-throughput technologies, time series/longitudinal high-throughput experiments have become possible and affordable. However, the development of statistical methods dealing with gene expression profiles across time points has not kept up with the explosion of such data. The feature selection process is of critical importance for longitudinal microarray data. In this study, we proposed aggregating a gene's expression values across time into a single value using the sign average method, thereby degrading a longitudinal feature selection process into a classic one. Regularized logistic regression models with pseudogenes (i.e., the sign average of genes across time as predictors) were then optimized by either the coordinate descent method or the threshold gradient descent regularization method. By applying the proposed methods to simulated data and a traumatic injury dataset, we have demonstrated that the proposed methods, especially for the combination of sign average and threshold gradient descent regularization, outperform other competitive algorithms. To conclude, the proposed methods are highly recommended for studies with the objective of carrying out feature selection for longitudinal gene expression data.

SUBMITTER: Tian S

PROVIDER: S-EPMC6444255 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Feature Selection for Longitudinal Data by Using Sign Averages to Summarize Gene Expression Values over Time.

Tian Suyan S Wang Chi C

BioMed research international 20190319

With the rapid evolution of high-throughput technologies, time series/longitudinal high-throughput experiments have become possible and affordable. However, the development of statistical methods dealing with gene expression profiles across time points has not kept up with the explosion of such data. The feature selection process is of critical importance for longitudinal microarray data. In this study, we proposed aggregating a gene's expression values across time into a single value using the ...[more]

PMID: 31016185

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Project description:BackgroundMachine learning methodologies are gaining popularity for developing medical prediction models for datasets with a large number of predictors, particularly in the setting of clustered and longitudinal data. Binary Mixed Model (BiMM) forest is a promising machine learning algorithm which may be applied to develop prediction models for clustered and longitudinal binary outcomes. Although machine learning methods for clustered and longitudinal methods such as BiMM forest exist, feature selection has not been analyzed via data simulations. Feature selection improves the practicality and ease of use of prediction models for clinicians by reducing the burden of data collection. Thus, feature selection procedures are not only beneficial, but are often necessary for development of medical prediction models. In this study, we aim to assess feature selection within the BiMM forest setting for modeling clustered and longitudinal binary outcomes.MethodsWe conducted a simulation study to compare BiMM forest with feature selection (backward elimination or stepwise selection) to standard generalized linear mixed model feature selection methods (shrinkage and backward elimination). We also evaluated feature selection methods to develop models predicting mobility disability in older adults using the Health, Aging and Body Composition Study dataset as an example utilization of the proposed methodology.ResultsBiMM forest with backward elimination generally offered higher computational efficiency, similar or higher predictive performance (accuracy and area under the receiver operating curve), and similar or higher ability to identify correct features compared to linear methods for the different simulated scenarios. For predicting mobility disability in older adults, methods generally performed similarly in terms of accuracy, area under the receiver operating curve, and specificity; however, BiMM forest with backward elimination had the highest sensitivity.ConclusionsThis study is novel because it is the first investigation of feature selection for developing random forest prediction models for clustered and longitudinal binary outcomes. Results from the simulation study reveal that BiMM forest with backward elimination has the highest accuracy (performance and identification of correct features) and lowest computation time compared to other feature selection methods in some scenarios and similar performance in other scenarios. Many informatics datasets have clustered and longitudinal outcomes and results from this study suggest that BiMM forest with backward elimination may be beneficial for developing medical prediction models.

Project description:BackgroundLongitudinal categorical variables are sometimes restricted in terms of how individuals transition between categories over time. For example, with a time-dependent measure of smoking categorised as never-smoker, ex-smoker, and current-smoker, current-smokers or ex-smokers cannot transition to a never-smoker at a subsequent wave. These longitudinal variables often contain missing values, however, there is little guidance on whether these restrictions need to be accommodated when using multiple imputation methods. Multiply imputing such missing values, ignoring the restrictions, could lead to implausible transitions.MethodsWe designed a simulation study based on the Longitudinal Study of Australian Children, where the target analysis was the association between (incomplete) maternal smoking and childhood obesity. We set varying proportions of data on maternal smoking to missing completely at random or missing at random. We compared the performance of fully conditional specification with multinomial and ordinal logistic imputation, and predictive mean matching, two-fold fully conditional specification, indicator based imputation under multivariate normal imputation with projected distance-based rounding, and continuous imputation under multivariate normal imputation with calibration, where each of these multiple imputation methods were applied, accounting for the restrictions using a semi-deterministic imputation procedure.ResultsOverall, we observed reduced bias when applying multiple imputation methods with restrictions, and fully conditional specification with predictive mean matching performed the best. Applying fully conditional specification and two-fold fully conditional specification for imputing nominal variables based on multinomial logistic regression had severe convergence issues. Both imputation methods under multivariate normal imputation produced biased estimates when restrictions were not accommodated, however, we observed substantial reductions in bias when restrictions were applied with continuous imputation under multivariate normal imputation with calibration.ConclusionIn a similar longitudinal setting we recommend the use of fully conditional specification with predictive mean matching, with restrictions applied during the imputation stage.

Dataset Information

Feature Selection for Longitudinal Data by Using Sign Averages to Summarize Gene Expression Values over Time.

Publications

Feature Selection for Longitudinal Data by Using Sign Averages to Summarize Gene Expression Values over Time.

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