A deep learning architecture for combining and imputing heterogeneous metabolomics datasets

Public metabolomics databases offer a large number of datasets. Combined analysis of these data sets may better capture complex molecular mechanisms in diseases. However, most datasets include measurements for only a very small fraction of the known metabolites. Hence, simply putting together these studies leads to very sparse datasets, which do not lend themselves well to training machine learning models. In this paper, we propose two novel approaches for dataset merging and imputation model training: (i) Iterative similarity-based merging generates an optimal merge set for each dataset and makes sure that a minimum sparsity threshold is maintained, and (ii) Model-guided agglomerative merging combines datasets in pairs to create a single large dataset in an attempt to effectively combine diverse metabolomics datasets while minimizing the likelihood of gaps created by non-overlapping metabolites. In both approaches, after creating joint datasets, Variational autoencoders (VAE) are employed for imputation model training. We evaluate our approach on the entire set of public datasets from the Metabolomics workbench. Our results demonstrate that the proposed approaches achieve significantly better imputation performance than the state-of-the-art approach.