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

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.Author summary: Missing 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 to 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 both of the real-world and simulated metabolomics datasets to demonstrate the superiority of our method from different perspectives.