Imputation of missing values in lipidomic datasets

Lipidomic data often exhibit missing data points, which can be categorized as missing completely at random (MCAR), missing at random, or missing not at random (MNAR). In order to utilize statistical methods that require complete datasets or to improve the identification of potential effects in statistical comparisons, imputation techniques can be employed. In this study, we investigate commonly used methods such as zero, half-minimum, mean, and median imputation, as well as more advanced techniques such as k-nearest neighbor and random forest imputation. We employ a combination of simulation-based approaches and application to real datasets to assess the performance and effectiveness of these methods. Shotgun lipidomics datasets exhibit high correlations and missing values, often due to low analyte abundance, characterized as MNAR. In this context, k-nearest neighbor approaches based on correlation and truncated normal distributions demonstrate best performance. Importantly, both methods can effectively impute missing values independent of the type of missingness, the determination of which is nearly impossible in practice. The imputation methods still control the type I error rate.