scholarly journals Multiple Imputation Approaches Applied to the Missing Value Problem in Bottom-Up Proteomics

2021 ◽  
Vol 22 (17) ◽  
pp. 9650
Author(s):  
Miranda L. Gardner ◽  
Michael A. Freitas
Keyword(s):  
Multiple Imputation ◽  
Missing At Random ◽  
Data Sets ◽  
Proteomics Data ◽  
Missing Not At Random ◽  
Differential Abundance ◽  
Missing Value ◽  
Bottom Up ◽  
Missing Value Imputation ◽  
Impute Data

Analysis of differential abundance in proteomics data sets requires careful application of missing value imputation. Missing abundance values widely vary when performing comparisons across different sample treatments. For example, one would expect a consistent rate of “missing at random” (MAR) across batches of samples and varying rates of “missing not at random” (MNAR) depending on the inherent difference in sample treatments within the study. The missing value imputation strategy must thus be selected that best accounts for both MAR and MNAR simultaneously. Several important issues must be considered when deciding the appropriate missing value imputation strategy: (1) when it is appropriate to impute data; (2) how to choose a method that reflects the combinatorial manner of MAR and MNAR that occurs in an experiment. This paper provides an evaluation of missing value imputation strategies used in proteomics and presents a case for the use of hybrid left-censored missing value imputation approaches that can handle the MNAR problem common to proteomics data.

scholarly journals Multiple Imputation Approaches Applied to the Missing Value Problem in Bottom-up Proteomics

2020 ◽  
Author(s):  
Miranda L. Gardner ◽  
Michael A. Freitas
Keyword(s):  
Multiple Imputation ◽  
Missing At Random ◽  
Data Sets ◽  
Proteomics Data ◽  
Missing Not At Random ◽  
Differential Abundance ◽  
Missing Value ◽  
Bottom Up ◽  
Missing Value Imputation ◽  
Impute Data

ABSTRACTAnalysis of differential abundance in proteomics data sets requires careful application of missing value imputation. Missing abundance values vary widely when performing comparisons across different sample treatments. For example, one would expect a consistent rate of “missing at random” (MAR) across batches of samples and varying rates of “missing not at random” (MNAR) depending on inherent difference in sample treatments within the study. The missing value imputation strategy must thus be selected that best accounts for both MAR and MNAR simultaneously. Several important issues must be considered when deciding the appropriate missing value imputation strategy: (1) when it is appropriate to impute data, (2) how to choose a method that reflects the combinatorial manner of MAR and MNAR that occurs in an experiment. This paper provides an evaluation of missing value imputation strategies used in proteomics and presents a case for the use of hybrid left-censored missing value imputation approaches that can handle the MNAR problem common to proteomics data.

A systematic review of machine learning-based missing value imputation techniques

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Tressy Thomas ◽  
Enayat Rajabi
Keyword(s):  
Machine Learning ◽  
Selection Process ◽  
Evaluation Metrics ◽  
Correct Prediction ◽  
Data Sets ◽  
Data Set ◽  
Missing Value ◽  
Content Type ◽  
Missing Value Imputation ◽  
Literature Reviews

PurposeThe primary aim of this study is to review the studies from different dimensions including type of methods, experimentation setup and evaluation metrics used in the novel approaches proposed for data imputation, particularly in the machine learning (ML) area. This ultimately provides an understanding about how well the proposed framework is evaluated and what type and ratio of missingness are addressed in the proposals. The review questions in this study are (1) what are the ML-based imputation methods studied and proposed during 2010–2020? (2) How the experimentation setup, characteristics of data sets and missingness are employed in these studies? (3) What metrics were used for the evaluation of imputation method?Design/methodology/approachThe review process went through the standard identification, screening and selection process. The initial search on electronic databases for missing value imputation (MVI) based on ML algorithms returned a large number of papers totaling at 2,883. Most of the papers at this stage were not exactly an MVI technique relevant to this study. The literature reviews are first scanned in the title for relevancy, and 306 literature reviews were identified as appropriate. Upon reviewing the abstract text, 151 literature reviews that are not eligible for this study are dropped. This resulted in 155 research papers suitable for full-text review. From this, 117 papers are used in assessment of the review questions.FindingsThis study shows that clustering- and instance-based algorithms are the most proposed MVI methods. Percentage of correct prediction (PCP) and root mean square error (RMSE) are most used evaluation metrics in these studies. For experimentation, majority of the studies sourced the data sets from publicly available data set repositories. A common approach is that the complete data set is set as baseline to evaluate the effectiveness of imputation on the test data sets with artificially induced missingness. The data set size and missingness ratio varied across the experimentations, while missing datatype and mechanism are pertaining to the capability of imputation. Computational expense is a concern, and experimentation using large data sets appears to be a challenge.Originality/valueIt is understood from the review that there is no single universal solution to missing data problem. Variants of ML approaches work well with the missingness based on the characteristics of the data set. Most of the methods reviewed lack generalization with regard to applicability. Another concern related to applicability is the complexity of the formulation and implementation of the algorithm. Imputations based on k-nearest neighbors (kNN) and clustering algorithms which are simple and easy to implement make it popular across various domains.

scholarly journals Weighted multiple imputation of ethnicity data that are missing not at random in primary care databases

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Tra My Pham ◽  
Irene Petersen ◽  
James Carpenter ◽  
Tim Morris
Keyword(s):  
Primary Care ◽  
Missing Data ◽  
Multiple Imputation ◽  
Simulation Study ◽  
Case Analysis ◽  
Missing At Random ◽  
Complete Case ◽  
Missing Not At Random ◽  
Health Records ◽  
Ethnicity Data

ABSTRACT BackgroundEthnicity is an important factor to be considered in health research because of its association with inequality in disease prevalence and the utilisation of healthcare. Ethnicity recording has been incorporated in primary care electronic health records, and hence is available in large UK primary care databases such as The Health Improvement Network (THIN). However, since primary care data are routinely collected for clinical purposes, a large amount of data that are relevant for research including ethnicity is often missing. A popular approach for missing data is multiple imputation (MI). However, the conventional MI method assuming data are missing at random does not give plausible estimates of the ethnicity distribution in THIN compared to the general UK population. This might be due to the fact that ethnicity data in primary care are likely to be missing not at random. ObjectivesI propose a new MI method, termed ‘weighted multiple imputation’, to deal with data that are missing not at random in categorical variables.MethodsWeighted MI combines MI and probability weights which are calculated using external data sources. Census summary statistics for ethnicity can be used to form weights in weighted MI such that the correct marginal ethnic breakdown is recovered in THIN. I conducted a simulation study to examine weighted MI when ethnicity data are missing not at random. In this simulation study which resembled a THIN dataset, ethnicity was an independent variable in a survival model alongside other covariates. Weighted MI was compared to the conventional MI and other traditional missing data methods including complete case analysis and single imputation.ResultsWhile a small bias was still present in ethnicity coefficient estimates under weighted MI, it was less severe compared to MI assuming missing at random. Complete case analysis and single imputation were inadequate to handle data that are missing not at random in ethnicity.ConclusionsAlthough not a total cure, weighted MI represents a pragmatic approach that has potential applications not only in ethnicity but also in other incomplete categorical health indicators in electronic health records.

Flexible, Free Software for Multilevel Multiple Imputation: A Review of Blimp and jomo

2019 ◽  
Vol 44 (5) ◽  
pp. 625-641
Author(s):  
Timothy Hayes
Keyword(s):  
Multiple Imputation ◽  
Interaction Model ◽  
Missing At Random ◽  
Analysis Model ◽  
Imputation Model ◽  
Model Following ◽  
Software Packages ◽  
Random Intercept ◽  
Impute Data ◽  
Multilevel Multiple Imputation

Multiple imputation is a popular method for addressing data that are presumed to be missing at random. To obtain accurate results, one’s imputation model must be congenial to (appropriate for) one’s intended analysis model. This article reviews and demonstrates two recent software packages, Blimp and jomo, to multiply impute data in a manner congenial with three prototypical multilevel modeling analyses: (1) a random intercept model, (2) a random slope model, and (3) a cross-level interaction model. Following these analysis examples, I review and discuss both software packages.

scholarly journals A Note on Listwise Deletion versus Multiple Imputation

2018 ◽  
Vol 26 (4) ◽  
pp. 480-488 ◽  
Author(s):  
Thomas B. Pepinsky
Keyword(s):  
Multiple Imputation ◽  
Missing Values ◽  
Missing At Random ◽  
Strong Correlations ◽  
Simulation Approach ◽  
Missing Not At Random ◽  
Listwise Deletion ◽  
Data Generating Process

This letter compares the performance of multiple imputation and listwise deletion using a simulation approach. The focus is on data that are “missing not at random” (MNAR), in which case both multiple imputation and listwise deletion are known to be biased. In these simulations, multiple imputation yields results that are frequently more biased, less efficient, and with worse coverage than listwise deletion when data are MNAR. This is the case even with very strong correlations between fully observed variables and variables with missing values, such that the data are very nearly “missing at random.” These results recommend caution when comparing the results from multiple imputation and listwise deletion, when the true data generating process is unknown.

scholarly journals Missing not at random in end of life care studies: multiple imputation and sensitivity analysis on data from the ACTION study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Giulia Carreras ◽  
◽  
Guido Miccinesi ◽  
Andrew Wilcock ◽  
Nancy Preston ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Multiple Imputation ◽  
End Of Life ◽  
End Of Life Care ◽  
Missing Values ◽  
Controlled Trial ◽  
Missing At Random ◽  
Life Care ◽  
Missing Not At Random ◽  
Cluster Randomized

Abstract Background Missing data are common in end-of-life care studies, but there is still relatively little exploration of which is the best method to deal with them, and, in particular, if the missing at random (MAR) assumption is valid or missing not at random (MNAR) mechanisms should be assumed. In this paper we investigated this issue through a sensitivity analysis within the ACTION study, a multicenter cluster randomized controlled trial testing advance care planning in patients with advanced lung or colorectal cancer. Methods Multiple imputation procedures under MAR and MNAR assumptions were implemented. Possible violation of the MAR assumption was addressed with reference to variables measuring quality of life and symptoms. The MNAR model assumed that patients with worse health were more likely to have missing questionnaires, making a distinction between single missing items, which were assumed to satisfy the MAR assumption, and missing values due to completely missing questionnaire for which a MNAR mechanism was hypothesized. We explored the sensitivity to possible departures from MAR on gender differences between key indicators and on simple correlations. Results Up to 39% of follow-up data were missing. Results under MAR reflected that missingness was related to poorer health status. Correlations between variables, although very small, changed according to the imputation method, as well as the differences in scores by gender, indicating a certain sensitivity of the results to the violation of the MAR assumption. Conclusions The findings confirmed the importance of undertaking this kind of analysis in end-of-life care studies.

scholarly journals Extending balance assessment for the generalized propensity score under multiple imputation

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna-Simone J. Frank ◽  
David S. Matteson ◽  
Hiroko K. Solvang ◽  
Angela Lupattelli ◽  
Hedvig Nordeng
Keyword(s):  
Propensity Score ◽  
Multiple Imputation ◽  
Simulated Data ◽  
Missing At Random ◽  
Estimation Bias ◽  
Data Sets ◽  
Balance Assessment ◽  
Generalized Propensity Score ◽  
Standardized Mean Difference ◽  
Definition Of

AbstractThis manuscript extends the definition of the Absolute Standardized Mean Difference (ASMD) for binary exposure (M = 2) to cases for M > 2 on multiple imputed data sets. The Maximal Maximized Standardized Difference (MMSD) and the Maximal Averaged Standardized Difference (MASD) were proposed. For different percentages, missing data were introduced in covariates in the simulated data based on the missing at random (MAR) assumption. We then investigate the performance of these two metric definitions using simulated data of full and imputed data sets. The performance of the MASD and the MMSD were validated by relating the balance metrics to estimation bias. The results show that there is an association between the balance metrics and bias. The proposed balance diagnostics seem therefore appropriate to assess balance for the generalized propensity score (GPS) under multiple imputation.

scholarly journals Multiple Imputation with Missing Indicators as Proxies for Unmeasured Variables: Simulation Study

2020 ◽  
Author(s):  
Matthew Sperrin ◽  
Glen P. Martin
Keyword(s):  
Missing Data ◽  
Multiple Imputation ◽  
Simulation Study ◽  
Causal Effect ◽  
Missing At Random ◽  
Directed Acyclic Graphs ◽  
Missing Not At Random ◽  
Routinely Collected Health Data ◽  
Effect Estimation ◽  
Minimal Bias

Abstract Background : Within routinely collected health data, missing data for an individual might provide useful information in itself. This occurs, for example, in the case of electronic health records, where the presence or absence of data is informative. While the naive use of missing indicators to try to exploit such information can introduce bias, its use in conjunction with multiple imputation may unlock the potential value of missingness to reduce bias in causal effect estimation, particularly in missing not at random scenarios and where missingness might be associated with unmeasured confounders. Methods: We conducted a simulation study to determine when the use of a missing indicator, combined with multiple imputation, would reduce bias for causal effect estimation, under a range of scenarios including unmeasured variables, missing not at random, and missing at random mechanisms. We use directed acyclic graphs and structural models to elucidate a variety of causal structures of interest. We handled missing data using complete case analysis, and multiple imputation with and without missing indicator terms. Results: We find that multiple imputation combined with a missing indicator gives minimal bias for causal effect estimation in most scenarios. In particular the approach: 1) does not introduce bias in missing (completely) at random scenarios; 2)reduces bias in missing not at random scenarios where the missing mechanism depends on the missing variable itself; and 3) may reduce or increase bias when unmeasured confounding is present. Conclusion : In the presence of missing data, careful use of missing indicators, combined with multiple imputation, can improve causal effect estimation when missingness is informative, and is not detrimental when missingness is at random.

Using the CES-D scale in a large cohort study and dealing with missing data: Application to the French E3N cohort

2011 ◽  
Vol 26 (S2) ◽  
pp. 572-572
Author(s):  
N. Resseguier ◽  
H. Verdoux ◽  
F. Clavel-Chapelon ◽  
X. Paoletti
Keyword(s):  
Sensitivity Analysis ◽  
Missing Data ◽  
Multiple Imputation ◽  
Missing Values ◽  
Large Population ◽  
Missing At Random ◽  
Population Based ◽  
Missing Value ◽  
Perform Sensitivity Analysis ◽  
The Impact

IntroductionThe CES-D scale is commonly used to assess depressive symptoms (DS) in large population-based studies. Missing values in items of the scale may create biases.ObjectivesTo explore reasons for not completing items of the CES-D scale and to perform sensitivity analysis of the prevalence of DS to assess the impact of different missing data hypotheses.Methods71412 women included in the French E3N cohort returned in 2005 a questionnaire containing the CES-D scale. 45% presented at least one missing value in the scale. An interview study was carried out on a random sample of 204 participants to examine the different hypotheses for the missing value mechanism. The prevalence of DS was estimated according to different methods for handling missing values: complete cases analysis, single imputation, multiple imputation under MAR (missing at random) and MNAR (missing not at random) assumptions.ResultsThe interviews showed that participants were not embarrassed to fill in questions about DS. Potential reasons of nonresponse were identified. MAR and MNAR hypotheses remained plausible and were explored.Among complete responders, the prevalence of DS was 26.1%. After multiple imputation under MAR assumption, it was 28.6%, 29.8% and 31.7% among women presenting up to 4, to 10 and to 20 missing values, respectively. The estimates were robust after applying various scenarios of MNAR data for the sensitivity analysis.ConclusionsThe CES-D scale can easily be used to assess DS in large cohorts. Multiple imputation under MAR assumption allows to reliably handle missing values.

scholarly journals GSimp: A Gibbs sampler based left-censored missing value imputation approach for metabolomics studies

2017 ◽  
Author(s):  
Runmin Wei ◽  
Jingye Wang ◽  
Erik Jia ◽  
Tianlu Chen ◽  
Yan Ni ◽  
...  
Keyword(s):  
Gibbs Sampler ◽  
Real World ◽  
Missing Values ◽  
Statistical Analyses ◽  
Targeted Metabolomics ◽  
Missing Not At Random ◽  
Missing Value ◽  
Imputation Methods ◽  
Missing Value Imputation ◽  
Imputation Approach

AbstractLeft-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 have 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. The R code for GSimp, evaluation pipeline, vignette, real-world and simulated targeted metabolomics datasets are available at: https://github.com/WandeRum/GSimp.Author summaryMissing values caused by the limit of detection/quantification (LOD/LOQ) were widely observed in mass spectrometry (MS)-based targeted metabolomics studies and could be recognized as missing not at random (MNAR). MNAR leads to biased parameter estimations and jeopardizes following statistical analyses in different aspects, such as distorting sample distribution, impairing statistical power, etc. Although a wide range of missing value imputation methods was developed for –omics studies, a limited number of methods was designed appropriately for the situation of MNAR currently. To alleviate problems caused by MNAR and facilitate targeted metabolomics studies, we developed a Gibbs sampler based missing value imputation approach, called GSimp, which is public-accessible on GitHub. And we compared our method with existing approaches using an imputation evaluation pipeline on real-world and simulated metabolomics datasets to demonstrate the superiority of our method from different perspectives.

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