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      Bias in random forest variable importance measures: Illustrations, sources and a solution

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          Abstract

          Background

          Variable importance measures for random forests have been receiving increased attention as a means of variable selection in many classification tasks in bioinformatics and related scientific fields, for instance to select a subset of genetic markers relevant for the prediction of a certain disease. We show that random forest variable importance measures are a sensible means for variable selection in many applications, but are not reliable in situations where potential predictor variables vary in their scale of measurement or their number of categories. This is particularly important in genomics and computational biology, where predictors often include variables of different types, for example when predictors include both sequence data and continuous variables such as folding energy, or when amino acid sequence data show different numbers of categories.

          Results

          Simulation studies are presented illustrating that, when random forest variable importance measures are used with data of varying types, the results are misleading because suboptimal predictor variables may be artificially preferred in variable selection. The two mechanisms underlying this deficiency are biased variable selection in the individual classification trees used to build the random forest on one hand, and effects induced by bootstrap sampling with replacement on the other hand.

          Conclusion

          We propose to employ an alternative implementation of random forests, that provides unbiased variable selection in the individual classification trees. When this method is applied using subsampling without replacement, the resulting variable importance measures can be used reliably for variable selection even in situations where the potential predictor variables vary in their scale of measurement or their number of categories. The usage of both random forest algorithms and their variable importance measures in the R system for statistical computing is illustrated and documented thoroughly in an application re-analyzing data from a study on RNA editing. Therefore the suggested method can be applied straightforwardly by scientists in bioinformatics research.

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          Most cited references33

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          R: A Language and Environment for Statistical Computing.

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            Random forest: a classification and regression tool for compound classification and QSAR modeling.

            A new classification and regression tool, Random Forest, is introduced and investigated for predicting a compound's quantitative or categorical biological activity based on a quantitative description of the compound's molecular structure. Random Forest is an ensemble of unpruned classification or regression trees created by using bootstrap samples of the training data and random feature selection in tree induction. Prediction is made by aggregating (majority vote or averaging) the predictions of the ensemble. We built predictive models for six cheminformatics data sets. Our analysis demonstrates that Random Forest is a powerful tool capable of delivering performance that is among the most accurate methods to date. We also present three additional features of Random Forest: built-in performance assessment, a measure of relative importance of descriptors, and a measure of compound similarity that is weighted by the relative importance of descriptors. It is the combination of relatively high prediction accuracy and its collection of desired features that makes Random Forest uniquely suited for modeling in cheminformatics.
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              Gene selection and classification of microarray data using random forest

              Background Selection of relevant genes for sample classification is a common task in most gene expression studies, where researchers try to identify the smallest possible set of genes that can still achieve good predictive performance (for instance, for future use with diagnostic purposes in clinical practice). Many gene selection approaches use univariate (gene-by-gene) rankings of gene relevance and arbitrary thresholds to select the number of genes, can only be applied to two-class problems, and use gene selection ranking criteria unrelated to the classification algorithm. In contrast, random forest is a classification algorithm well suited for microarray data: it shows excellent performance even when most predictive variables are noise, can be used when the number of variables is much larger than the number of observations and in problems involving more than two classes, and returns measures of variable importance. Thus, it is important to understand the performance of random forest with microarray data and its possible use for gene selection. Results We investigate the use of random forest for classification of microarray data (including multi-class problems) and propose a new method of gene selection in classification problems based on random forest. Using simulated and nine microarray data sets we show that random forest has comparable performance to other classification methods, including DLDA, KNN, and SVM, and that the new gene selection procedure yields very small sets of genes (often smaller than alternative methods) while preserving predictive accuracy. Conclusion Because of its performance and features, random forest and gene selection using random forest should probably become part of the "standard tool-box" of methods for class prediction and gene selection with microarray data.
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                Author and article information

                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                2007
                25 January 2007
                : 8
                : 25
                Affiliations
                [1 ]Institut für Statistik, Ludwig-Maximilians-Universität München, Ludwigstr. 33, 80539 München, Germany
                [2 ]Institut für medizinische Statistik und Epidemiologie, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany
                [3 ]Department für Statistik und Mathematik, Wirtschaftsuniversität Wien, Augasse 2-6, 1090 Wien, Austria
                [4 ]Institut für Medizininformatik, Biometrie und Epidemiologie, Friedrich-Alexander-Universtität Erlangen-Nürnberg, Waldstr. 6, D-91054 Erlangen, Germany
                Article
                1471-2105-8-25
                10.1186/1471-2105-8-25
                1796903
                17254353
                ca63e173-e90c-4ad4-b831-a4780a903e7d
                Copyright © 2007 Strobl et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 September 2006
                : 25 January 2007
                Categories
                Methodology Article

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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