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Comparison of Statistical Testing and Predictive Analysis Methods for Feature Selection in Zero-inflated Microbiome Data

Date

2019-04-09

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Thesis

Degree Level

Masters

Abstract

Background: Recent advances in next-generation sequencing (NGS) technology enable researchers to collect a large volume of microbiome data. Microbiome data consist of operational taxonomic unit (OTU) count data characterized by zero-inflation, over-dispersion, and grouping structure among the sample. Currently, statistical testing methods based on generalized linear mixed effect models (GLMM) are commonly performed to identify OTUs that are associated with a phenotype such as human diseases or plant traits. There are a number of limitations for statistical testing methods including these two: (1) the validity of p-value/q-value depends sensitively on the correctness of models, and (2) the statistical significance does not necessarily imply predictivity. Statistic testing methods depend on model correctness and attempt to select ”marginally relevant” features, not the most predictive ones. Predictive analysis using methods such as LASSO is an alternative approach for feature selection. To the best of our knowledge, this approach has not been used widely for analyzing microbiome data. Methodology: We use four synthetic datasets simulated from zero-inflated negative binomial distribution and a real human gut microbiome data to compare the feature selection performance of LASSO with the likelihood ratio test methods applied to GLMMs. We also investigate the performance of cross-validation in estimating the out-of-sample predictivity of selected features in zero-inflated data. Results: Our studies with synthetic datasets show that the feature selection performance of LASSO is remarkably excellent in zero-inflated data and is comparable with the likelihood ratio test applied to the true data generating model. The feature selection performance of LASSO is better when the distributions of counts are more differentiated by the phenotype, which is a categorical variable in our synthetic datasets. In addition, we performed LOOCV on the train set and out-of-sample prediction on the test set. The performance of the cross-validatory (CV) predictive measures are very close to the out-of-sample predictivity measures. This indicates that LOOCV predictive metrics provide honest measures of the predictivity of the features selected by LASSO. Therefore, the CV predictive measures are good guidance for choosing cutoffs (shrinkage parameter $\lambda$) in selecting features with LASSO. By contrast, when wrong models are fitted to a dataset, the differences between the q-values and the actual false discovery rates are huge; hence, their q-values are tremendously misleading for selecting features. Our comparison of LASSO and statistical testing methods (likelihood ratio test in our analysis) in the real dataset shows that small q-values do not necessarily imply high predictivity of the selected OTUs. However, the researchers often use q-values to find the predictors. That is why we need to look at q-values carefully. Conclusions: Statistical testing methods perform greatly in zero-inflated datasets on both synthetic and real data. However, a serious model checking should be conducted before we use q-values to choose features. Predictive analysis with LASSO is recommended to supplement q-values for selecting features and for measuring the predictivity of selected features.

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Keywords

Generalized Linear Mixed Model, Least Absolute Shrinkage and Selection Operator, Likelihood Ratio Test, False Discovery Rate, Leave-One-Out Cross-Validation

Citation

Degree

Master of Science (M.Sc.)

Department

Mathematics and Statistics

Program

Mathematics

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