Dataset Information

Biological impact of missing-value imputation on downstream analyses of gene expression profiles.

ABSTRACT:

Motivation

Microarray experiments frequently produce multiple missing values (MVs) due to flaws such as dust, scratches, insufficient resolution or hybridization errors on the chips. Unfortunately, many downstream algorithms require a complete data matrix. The motivation of this work is to determine the impact of MV imputation on downstream analysis, and whether ranking of imputation methods by imputation accuracy correlates well with the biological impact of the imputation.

Methods

Using eight datasets for differential expression (DE) and classification analysis and eight datasets for gene clustering, we demonstrate the biological impact of missing-value imputation on statistical downstream analyses, including three commonly employed DE methods, four classifiers and three gene-clustering methods. Correlation between the rankings of imputation methods based on three root-mean squared error (RMSE) measures and the rankings based on the downstream analysis methods was used to investigate which RMSE measure was most consistent with the biological impact measures, and which downstream analysis methods were the most sensitive to the choice of imputation procedure.

Results

DE was the most sensitive to the choice of imputation procedure, while classification was the least sensitive and clustering was intermediate between the two. The logged RMSE (LRMSE) measure had the highest correlation with the imputation rankings based on the DE results, indicating that the LRMSE is the best representative surrogate among the three RMSE-based measures. Bayesian principal component analysis and least squares adaptive appeared to be the best performing methods in the empirical downstream evaluation.

SUBMITTER: Oh S

PROVIDER: S-EPMC3008641 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

Biological impact of missing-value imputation on downstream analyses of gene expression profiles.

Oh Sunghee S Kang Dongwan D DD Brock Guy N GN Tseng George C GC

Bioinformatics (Oxford, England) 20101102 1

<h4>Motivation</h4>Microarray experiments frequently produce multiple missing values (MVs) due to flaws such as dust, scratches, insufficient resolution or hybridization errors on the chips. Unfortunately, many downstream algorithms require a complete data matrix. The motivation of this work is to determine the impact of MV imputation on downstream analysis, and whether ranking of imputation methods by imputation accuracy correlates well with the biological impact of the imputation.<h4>Methods</ ...[more]

PMID: 21045072

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Project description:BackgroundEpistatic miniarray profiling (E-MAPs) is a high-throughput approach capable of quantifying aggravating or alleviating genetic interactions between gene pairs. The datasets resulting from E-MAP experiments typically take the form of a symmetric pairwise matrix of interaction scores. These datasets have a significant number of missing values - up to 35% - that can reduce the effectiveness of some data analysis techniques and prevent the use of others. An effective method for imputing interactions would therefore increase the types of possible analysis, as well as increase the potential to identify novel functional interactions between gene pairs. Several methods have been developed to handle missing values in microarray data, but it is unclear how applicable these methods are to E-MAP data because of their pairwise nature and the significantly larger number of missing values. Here we evaluate four alternative imputation strategies, three local (Nearest neighbor-based) and one global (PCA-based), that have been modified to work with symmetric pairwise data.ResultsWe identify different categories for the missing data based on their underlying cause, and show that values from the largest category can be imputed effectively. We compare local and global imputation approaches across a variety of distinct E-MAP datasets, showing that both are competitive and preferable to filling in with zeros. In addition we show that these methods are effective in an E-MAP from a different species, suggesting that pairwise imputation techniques will be increasingly useful as analogous epistasis mapping techniques are developed in different species. We show that strongly alleviating interactions are significantly more difficult to predict than strongly aggravating interactions. Finally we show that imputed interactions, generated using nearest neighbor methods, are enriched for annotations in the same manner as measured interactions. Therefore our method potentially expands the number of mapped epistatic interactions. In addition we make implementations of our algorithms available for use by other researchers.ConclusionsWe address the problem of missing value imputation for E-MAPs, and suggest the use of symmetric nearest neighbor based approaches as they offer consistently accurate imputations across multiple datasets in a tractable manner.

Project description:BackgroundIn modern biomedical research of complex diseases, a large number of demographic and clinical variables, herein called phenomic data, are often collected and missing values (MVs) are inevitable in the data collection process. Since many downstream statistical and bioinformatics methods require complete data matrix, imputation is a common and practical solution. In high-throughput experiments such as microarray experiments, continuous intensities are measured and many mature missing value imputation methods have been developed and widely applied. Numerous methods for missing data imputation of microarray data have been developed. Large phenomic data, however, contain continuous, nominal, binary and ordinal data types, which void application of most methods. Though several methods have been developed in the past few years, not a single complete guideline is proposed with respect to phenomic missing data imputation.ResultsIn this paper, we investigated existing imputation methods for phenomic data, proposed a self-training selection (STS) scheme to select the best imputation method and provide a practical guideline for general applications. We introduced a novel concept of "imputability measure" (IM) to identify missing values that are fundamentally inadequate to impute. In addition, we also developed four variations of K-nearest-neighbor (KNN) methods and compared with two existing methods, multivariate imputation by chained equations (MICE) and missForest. The four variations are imputation by variables (KNN-V), by subjects (KNN-S), their weighted hybrid (KNN-H) and an adaptively weighted hybrid (KNN-A). We performed simulations and applied different imputation methods and the STS scheme to three lung disease phenomic datasets to evaluate the methods. An R package "phenomeImpute" is made publicly available.ConclusionsSimulations and applications to real datasets showed that MICE often did not perform well; KNN-A, KNN-H and random forest were among the top performers although no method universally performed the best. Imputation of missing values with low imputability measures increased imputation errors greatly and could potentially deteriorate downstream analyses. The STS scheme was accurate in selecting the optimal method by evaluating methods in a second layer of missingness simulation. All source files for the simulation and the real data analyses are available on the author's publication website.

Dataset Information

Biological impact of missing-value imputation on downstream analyses of gene expression profiles.

Motivation

Methods

Results

Publications

Biological impact of missing-value imputation on downstream analyses of gene expression profiles.

Similar Datasets

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