NMF-Based Approach for Missing Values Imputation of Mass Spectrometry Metabolomics Data.
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ABSTRACT:
SUBMITTER: Xu J
PROVIDER: S-EPMC8510447 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Missing values exist widely in mass-spectrometry (MS) based metabolomics data. Various methods have been applied for handling missing values, but the selection can significantly affect following data analyses. Typically, there are three types of missing values, missing not at random (MNAR), missing at random (MAR), and missing completely at random (MCAR). Our study comprehensively compared eight imputation methods (zero, half minimum (HM), mean, median, random forest (RF), singular value decomposition (SVD), k-nearest neighbors (kNN), and quantile regression imputation of left-censored data (QRILC)) for different types of missing values using four metabolomics datasets. Normalized root mean squared error (NRMSE) and NRMSE-based sum of ranks (SOR) were applied to evaluate imputation accuracy. Principal component analysis (PCA)/partial least squares (PLS)-Procrustes analysis were used to evaluate the overall sample distribution. Student's t-test followed by correlation analysis was conducted to evaluate the effects on univariate statistics. Our findings demonstrated that RF performed the best for MCAR/MAR and QRILC was the favored one for left-censored MNAR. Finally, we proposed a comprehensive strategy and developed a public-accessible web-tool for the application of missing value imputation in metabolomics ( https://metabolomics.cc.hawaii.edu/software/MetImp/ ).
| S-EPMC5766532 | biostudies-literature
Project description:When analyzing large datasets from high-throughput technologies, researchers often encounter missing quantitative measurements, which are particularly frequent in metabolomics datasets. Metabolomics, the comprehensive profiling of metabolite abundances, are typically measured using mass spectrometry technologies that often introduce missingness via multiple mechanisms: (1) the metabolite signal may be smaller than the instrument limit of detection; (2) the conditions under which the data are collected and processed may lead to missing values; (3) missing values can be introduced randomly. Missingness resulting from mechanism (1) would be classified as Missing Not At Random (MNAR), that from mechanism (2) would be Missing At Random (MAR), and that from mechanism (3) would be classified as Missing Completely At Random (MCAR). Two common approaches for handling missing data are the following: (1) omit missing data from the analysis; (2) impute the missing values. Both approaches may introduce bias and reduce statistical power in downstream analyses such as testing metabolite associations with clinical variables. Further, standard imputation methods in metabolomics often ignore the mechanisms causing missingness and inaccurately estimate missing values within a data set. We propose a mechanism-aware imputation algorithm that leverages a two-step approach in imputing missing values. First, we use a random forest classifier to classify the missing mechanism for each missing value in the data set. Second, we impute each missing value using imputation algorithms that are specific to the predicted missingness mechanism (i.e., MAR/MCAR or MNAR). Using complete data, we conducted simulations, where we imposed different missingness patterns within the data and tested the performance of combinations of imputation algorithms. Our proposed algorithm provided imputations closer to the original data than those using only one imputation algorithm for all the missing values. Consequently, our two-step approach was able to reduce bias for improved downstream analyses.
| S-EPMC9109373 | biostudies-literature
Project description:BackgroundData collected by an actigraphy device worn on the wrist or waist can provide objective measurements for studies related to physical activity; however, some data may contain intervals where values are missing. In previous studies, statistical methods have been applied to impute missing values on the basis of statistical assumptions. Deep learning algorithms, however, can learn features from the data without any such assumptions and may outperform previous approaches in imputation tasks.ObjectiveThe aim of this study was to impute missing values in data using a deep learning approach.MethodsTo develop an imputation model for missing values in accelerometer-based actigraphy data, a denoising convolutional autoencoder was adopted. We trained and tested our deep learning-based imputation model with the National Health and Nutrition Examination Survey data set and validated it with the external Korea National Health and Nutrition Examination Survey and the Korean Chronic Cerebrovascular Disease Oriented Biobank data sets which consist of daily records measuring activity counts. The partial root mean square error and partial mean absolute error of the imputed intervals (partial RMSE and partial MAE, respectively) were calculated using our deep learning-based imputation model (zero-inflated denoising convolutional autoencoder) as well as using other approaches (mean imputation, zero-inflated Poisson regression, and Bayesian regression).ResultsThe zero-inflated denoising convolutional autoencoder exhibited a partial RMSE of 839.3 counts and partial MAE of 431.1 counts, whereas mean imputation achieved a partial RMSE of 1053.2 counts and partial MAE of 545.4 counts, the zero-inflated Poisson regression model achieved a partial RMSE of 1255.6 counts and partial MAE of 508.6 counts, and Bayesian regression achieved a partial RMSE of 924.5 counts and partial MAE of 605.8 counts.ConclusionsOur deep learning-based imputation model performed better than the other methods when imputing missing values in actigraphy data.
| S-EPMC7413283 | biostudies-literature
Project description:Mass spectrometry is a modern and sophisticated high-throughput analytical technique that enables large-scale metabolomic analyses. It yields a high-dimensional large-scale matrix (samples × metabolites) of quantified data that often contain missing cells in the data matrix as well as outliers that originate for several reasons, including technical and biological sources. Although several missing data imputation techniques are described in the literature, all conventional existing techniques only solve the missing value problems. They do not relieve the problems of outliers. Therefore, outliers in the dataset decrease the accuracy of the imputation. We developed a new kernel weight function-based proposed missing data imputation technique that resolves the problems of missing values and outliers. We evaluated the performance of the proposed method and other conventional and recently developed missing imputation techniques using both artificially generated data and experimentally measured data analysis in both the absence and presence of different rates of outliers. Performances based on both artificial data and real metabolomics data indicate the superiority of our proposed kernel weight-based missing data imputation technique to the existing alternatives. For user convenience, an R package of the proposed kernel weight-based missing value imputation technique was developed, which is available at https://github.com/NishithPaul/tWLSA .
| S-EPMC8159923 | biostudies-literature
Project description:In this paper we propose a latent class based multiple imputation approach for analyzing missing categorical covariate data in a highly stratified data model. In this approach, we impute the missing data assuming a latent class imputation model and we use likelihood methods to analyze the imputed data. Via extensive simulations, we study its statistical properties and make comparisons with complete case analysis, multiple imputation, saturated log-linear multiple imputation and the Expectation- Maximization approach under seven missing data mechanisms (including missing completely at random, missing at random and not missing at random). These methods are compared with respect to bias, asymptotic standard error, type I error, and 95% coverage probabilities of parameter estimates. Simulations show that, under many missingness scenarios, latent class multiple imputation performs favorably when jointly considering these criteria. A data example from a matched case-control study of the association between multiple myeloma and polymorphisms of the Inter-Leukin 6 genes is considered.
| S-EPMC6290917 | biostudies-literature
Project description:BackgroundAssessing the reproducibility of measurements is an important first step for improving the reliability of downstream analyses of high-throughput metabolomics experiments. We define a metabolite to be reproducible when it demonstrates consistency across replicate experiments. Similarly, metabolites which are not consistent across replicates can be labeled as irreproducible. In this work, we introduce and evaluate the use (Ma)ximum (R)ank (R)eproducibility (MaRR) to examine reproducibility in mass spectrometry-based metabolomics experiments. We examine reproducibility across technical or biological samples in three different mass spectrometry metabolomics (MS-Metabolomics) data sets.ResultsWe apply MaRR, a nonparametric approach that detects the change from reproducible to irreproducible signals using a maximal rank statistic. The advantage of using MaRR over model-based methods that it does not make parametric assumptions on the underlying distributions or dependence structures of reproducible metabolites. Using three MS Metabolomics data sets generated in the multi-center Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) study, we applied the MaRR procedure after data processing to explore reproducibility across technical or biological samples. Under realistic settings of MS-Metabolomics data, the MaRR procedure effectively controls the False Discovery Rate (FDR) when there was a gradual reduction in correlation between replicate pairs for less highly ranked signals. Simulation studies also show that the MaRR procedure tends to have high power for detecting reproducible metabolites in most situations except for smaller values of proportion of reproducible metabolites. Bias (i.e., the difference between the estimated and the true value of reproducible signal proportions) values for simulations are also close to zero. The results reported from the real data show a higher level of reproducibility for technical replicates compared to biological replicates across all the three different datasets. In summary, we demonstrate that the MaRR procedure application can be adapted to various experimental designs, and that the nonparametric approach performs consistently well.ConclusionsThis research was motivated by reproducibility, which has proven to be a major obstacle in the use of genomic findings to advance clinical practice. In this paper, we developed a data-driven approach to assess the reproducibility of MS-Metabolomics data sets. The methods described in this paper are implemented in the open-source R package marr, which is freely available from Bioconductor at http://bioconductor.org/packages/marr .
| S-EPMC8424977 | biostudies-literature
Project description:BACKGROUND:Untargeted mass spectrometry (MS)-based metabolomics data often contain missing values that reduce statistical power and can introduce bias in biomedical studies. However, a systematic assessment of the various sources of missing values and strategies to handle these data has received little attention. Missing data can occur systematically, e.g. from run day-dependent effects due to limits of detection (LOD); or it can be random as, for instance, a consequence of sample preparation. METHODS:We investigated patterns of missing data in an MS-based metabolomics experiment of serum samples from the German KORA F4 cohort (n?=?1750). We then evaluated 31 imputation methods in a simulation framework and biologically validated the results by applying all imputation approaches to real metabolomics data. We examined the ability of each method to reconstruct biochemical pathways from data-driven correlation networks, and the ability of the method to increase statistical power while preserving the strength of established metabolic quantitative trait loci. RESULTS:Run day-dependent LOD-based missing data accounts for most missing values in the metabolomics dataset. Although multiple imputation by chained equations performed well in many scenarios, it is computationally and statistically challenging. K-nearest neighbors (KNN) imputation on observations with variable pre-selection showed robust performance across all evaluation schemes and is computationally more tractable. CONCLUSION:Missing data in untargeted MS-based metabolomics data occur for various reasons. Based on our results, we recommend that KNN-based imputation is performed on observations with variable pre-selection since it showed robust results in all evaluation schemes.
| S-EPMC6153696 | biostudies-literature
Project description:Left-censored missing values commonly exist in targeted metabolomics datasets and can be considered as missing not at random (MNAR). Improper data processing procedures for missing values will cause adverse impacts on subsequent statistical analyses. However, few imputation methods have been developed and applied to the situation of MNAR in the field of metabolomics. Thus, a practical left-censored missing value imputation method is urgently needed. We developed an iterative Gibbs sampler based left-censored missing value imputation approach (GSimp). We compared GSimp with other three imputation methods on two real-world targeted metabolomics datasets and one simulation dataset using our imputation evaluation pipeline. The results show that GSimp outperforms other imputation methods in terms of imputation accuracy, observation distribution, univariate and multivariate analyses, and statistical sensitivity. Additionally, a parallel version of GSimp was developed for dealing with large scale metabolomics datasets. The R code for GSimp, evaluation pipeline, tutorial, real-world and simulated targeted metabolomics datasets are available at: https://github.com/WandeRum/GSimp.
| S-EPMC5809088 | biostudies-literature
Project description:The real-world data analysis and processing using data mining techniques often are facing observations that contain missing values. The main challenge of mining datasets is the existence of missing values. The missing values in a dataset should be imputed using the imputation method to improve the data mining methods' accuracy and performance. There are existing techniques that use k-nearest neighbors algorithm for imputing the missing values but determining the appropriate k value can be a challenging task. There are other existing imputation techniques that are based on hard clustering algorithms. When records are not well-separated, as in the case of missing data, hard clustering provides a poor description tool in many cases. In general, the imputation depending on similar records is more accurate than the imputation depending on the entire dataset's records. Improving the similarity among records can result in improving the imputation performance. This paper proposes two numerical missing data imputation methods. A hybrid missing data imputation method is initially proposed, called KI, that incorporates k-nearest neighbors and iterative imputation algorithms. The best set of nearest neighbors for each missing record is discovered through the records similarity by using the k-nearest neighbors algorithm (kNN). To improve the similarity, a suitable k value is estimated automatically for the kNN. The iterative imputation method is then used to impute the missing values of the incomplete records by using the global correlation structure among the selected records. An enhanced hybrid missing data imputation method is then proposed, called FCKI, which is an extension of KI. It integrates fuzzy c-means, k-nearest neighbors, and iterative imputation algorithms to impute the missing data in a dataset. The fuzzy c-means algorithm is selected because the records can belong to multiple clusters at the same time. This can lead to further improvement for similarity. FCKI searches a cluster, instead of the whole dataset, to find the best k-nearest neighbors. It applies two levels of similarity to achieve a higher imputation accuracy. The performance of the proposed imputation techniques is assessed by using fifteen datasets with variant missing ratios for three types of missing data; MCAR, MAR, MNAR. These different missing data types are generated in this work. The datasets with different sizes are used in this paper to validate the model. Therefore, proposed imputation techniques are compared with other missing data imputation methods by means of three measures; the root mean square error (RMSE), the normalized root mean square error (NRMSE), and the mean absolute error (MAE). The results show that the proposed methods achieve better imputation accuracy and require significantly less time than other missing data imputation methods.
| S-EPMC8323724 | biostudies-literature
Project description:The analysis of high-throughput metabolomics mass spectrometry data across multiple biological sample types (biospecimens) poses challenges due to missing data. During differential abundance analysis, dropping samples with missing values can lead to severe loss of data as well as biased results in group comparisons and effect size estimates. However, the imputation of missing data (the process of replacing missing data with estimated values such as a mean) may compromise the inherent intra-subject correlation of a metabolite across multiple biospecimens from the same subject, which in turn may compromise the efficacy of the statistical analysis of differential metabolites in biomarker discovery. We investigated imputation strategies when considering multiple biospecimens from the same subject. We compared a novel, but simple, approach that consists of combining the two biospecimen data matrices (rows and columns of subjects and metabolites) and imputes the two biospecimen data matrices together to an approach that imputes each biospecimen data matrix separately. We then compared the bias in the estimation of the intra-subject multi-specimen correlation and its effects on the validity of statistical significance tests between two approaches. The combined approach to multi-biospecimen studies has not been evaluated previously even though it is intuitive and easy to implement. We examine these two approaches for five imputation methods: random forest, k nearest neighbor, expectation-maximization with bootstrap, quantile regression, and half the minimum observed value. Combining the biospecimen data matrices for imputation did not greatly increase efficacy in conserving the correlation structure or improving accuracy in the statistical conclusions for most of the methods examined. Random forest tended to outperform the other methods in all performance metrics, except specificity.
| S-EPMC9317643 | biostudies-literature