Multivariate Time Series Imputation: An Approach Based on Dictionary Learning.

The problem addressed by dictionary learning (DL) is the representation of data as a sparse linear combination of columns of a matrix called dictionary. Both the dictionary and the sparse representations are learned from the data. We show how DL can be employed in the imputation of multivariate time series. We use a structured dictionary, which is comprised of one block for each time series and a common block for all the time series. The size of each block and the sparsity level of the representation are selected by using information theoretic criteria. The objective function used in learning is designed to minimize either the sum of the squared errors or the sum of the magnitudes of the errors. We propose dimensionality reduction techniques for the case of high-dimensional time series. For demonstrating how the new algorithms can be used in practical applications, we conduct a large set of experiments on five real-life data sets. The missing data (MD) are simulated according to various scenarios where both the percentage of MD and the length of the sequences of MD are considered. This allows us to identify the situations in which the novel DL-based methods are superior to the existing methods.

Reconstructing the blood metabolome and genotype using long-range chromatin interactions.

BACKGROUND: -Maintenance of tight controls on circulating blood metabolites is crucial to normal, healthy tissue and organismal function. A number of single nucleotide polymorphisms (SNPs) have been associated with changes in the levels of blood metabolites. However, the impacts of the metabolite-associated SNPs are largely unknown because they fall within non-coding regions of the genome. OBJECTIVE: -We aimed to identify genes and tissues that are linked to changes in circulating blood metabolites by characterizing genome-wide spatial regulatory interactions involving blood metabolite-associated SNPs. METHOD: -We systematically integrated chromatin interaction (Hi-C), expression quantitative trait loci (eQTL), gene ontology, drug interaction, and literature-supported connections to deconvolute the genetic regulatory influences of 145 blood metabolite-associated SNPs. FINDINGS: -We identified 577 genes that are regulated by 130 distal and proximal metabolite-associated SNPs across 48 different human tissues. The affected genes are enriched in categories that include metabolism, enzymes, plasma proteins, disease development, and potential drug targets. Our results suggest that regulatory interactions in other tissues contribute to the modulation of blood metabolites. CONCLUSIONS: -The spatial SNP-gene-metabolite associations identified in this study expand on the list of genes and tissues that are influenced by metabolic-associated SNPs and improves our understanding of the molecular mechanisms underlying pathologic blood metabolite levels.