Abstract

BackgroundThe imputation of missing values is necessary for the efficient use of DNA microarray data, because many clustering algorithms and some statistical analysis require a complete data set. A few imputation methods for DNA microarray data have been introduced, but the efficiency of the methods was low and the validity of imputed values in these methods had not been fully checked.ResultsWe developed a new cluster-based imputation method called sequential K-nearest neighbor (SKNN) method. This imputes the missing values sequentially from the gene having least missing values, and uses the imputed values for the later imputation. Although it uses the imputed values, the efficiency of this new method is greatly improved in its accuracy and computational complexity over the conventional KNN-based method and other methods based on maximum likelihood estimation. The performance of SKNN was in particular higher than other imputation methods for the data with high missing rates and large number of experiments.Application of Expectation Maximization (EM) to the SKNN method improved the accuracy, but increased computational time proportional to the number of iterations. The Multiple Imputation (MI) method, which is well known but not applied previously to microarray data, showed a similarly high accuracy as the SKNN method, with slightly higher dependency on the types of data sets.ConclusionsSequential reuse of imputed data in KNN-based imputation greatly increases the efficiency of imputation. The SKNN method should be practically useful to save the data of some microarray experiments which have high amounts of missing entries. The SKNN method generates reliable imputed values which can be used for further cluster-based analysis of microarray data.

Highlights

  • The imputation of missing values is necessary for the efficient use of DNA microarray data, because many clustering algorithms and some statistical analysis require a complete data set

  • The sequential K-nearest neighbor (SKNN) method should be practically useful to save the data of some microarray experiments which have high amounts of missing entries

  • The SKNN method generates reliable imputed values which can be used for further cluster-based analysis of microarray data

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Summary

Introduction

The imputation of missing values is necessary for the efficient use of DNA microarray data, because many clustering algorithms and some statistical analysis require a complete data set. DNA microarray is a popular high-throughput technology for the monitoring of thousands of gene expression levels simultaneously under different conditions [1]. The analysis performed to meet the purposes of microarray studies mentioned above usually involves clustering genes according to their pattern of expression levels in various experimental conditions. Principal component analysis (PCA) is a powerful technique when used with the clustering method to specify the number of clusters[5]. These widely-used methods in microarray data analysis can be both seriously biased and misled by missing values in the dataset[6,7,8]

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