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Assumption Adequacy Averaging as a Concept to Develop More Robust Methods for Differential Gene Expression Analysis.

ABSTRACT: The concept of assumption adequacy averaging is introduced as a technique to develop more robust methods that incorporate assessments of assumption adequacy into the analysis. The concept is illustrated by using it to develop a method that averages results from the t-test and nonparametric rank-sum test with weights obtained from using the Shapiro-Wilk test to test the assumption of normality. Through this averaging process, the proposed method is able to rely more heavily on the statistical test that the data suggests is superior for each individual gene. Subsequently, this method developed by assumption adequacy averaging outperforms its two component methods (the t-test and rank-sum test) in a series of traditional and bootstrap-based simulation studies. The proposed method showed greater concordance in gene selection across two studies of gene expression in acute myeloid leukemia than did the t-test or rank-sum test. An R routine to implement the method is available upon request.

SUBMITTER: Pounds S

PROVIDER: S-EPMC2678745 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Assumption Adequacy Averaging as a Concept to Develop More Robust Methods for Differential Gene Expression Analysis.

Pounds Stan S Rai Shesh N SN

Computational statistics & data analysis 20090301 5

The concept of assumption adequacy averaging is introduced as a technique to develop more robust methods that incorporate assessments of assumption adequacy into the analysis. The concept is illustrated by using it to develop a method that averages results from the t-test and nonparametric rank-sum test with weights obtained from using the Shapiro-Wilk test to test the assumption of normality. Through this averaging process, the proposed method is able to rely more heavily on the statistical tes ...[more]

PMID: 20161327

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Project description:BackgroundDespite the availability of many ready-made testing software, reliable detection of differentially expressed genes in RNA-seq data is not a trivial task. Even though the data collection is considered high-throughput, data analysis has intricacies that require careful human attention. Researchers should use modern data analysis techniques that incorporate visual feedback to verify the appropriateness of their models. While some RNA-seq packages provide static visualization tools, their capabilities should be expanded and their meaningfulness should be explicitly demonstrated to users.ResultsIn this paper, we 1) introduce new interactive RNA-seq visualization tools, 2) compile a collection of examples that demonstrate to biologists why visualization should be an integral component of differential expression analysis. We use public RNA-seq datasets to show that our new visualization tools can detect normalization issues, differential expression designation problems, and common analysis errors. We also show that our new visualization tools can identify genes of interest in ways undetectable with models. Our R package "bigPint" includes the plotting tools introduced in this paper, many of which are unique additions to what is currently available. The "bigPint" website is located at https://lindsayrutter.github.io/bigPint and contains short vignette articles that introduce new users to our package, all written in reproducible code.ConclusionsWe emphasize that interactive graphics should be an indispensable component of modern RNA-seq analysis, which is currently not the case. This paper and its corresponding software aim to persuade 1) users to slightly modify their differential expression analyses by incorporating statistical graphics into their usual analysis pipelines, 2) developers to create additional complex and interactive plotting methods for RNA-seq data, possibly using lessons learned from our open-source codes. We hope our work will serve a small part in upgrading the RNA-seq analysis world into one that more wholistically extracts biological information using both models and visuals.

Dataset Information

Assumption Adequacy Averaging as a Concept to Develop More Robust Methods for Differential Gene Expression Analysis.

Publications

Assumption Adequacy Averaging as a Concept to Develop More Robust Methods for Differential Gene Expression Analysis.

Similar Datasets

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