BackgroundMetabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism's metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological, and many other applied biological domains. Its computationally intensive nature has driven requirements for open data formats, data repositories, and data analysis tools. However, the rapid progress has resulted in a mosaic of independent, and sometimes incompatible, analysis methods that are difficult to connect into a useful and complete data analysis solution.FindingsPhenoMeNal (Phenome and Metabolome aNalysis) is an advanced and complete solution to set up Infrastructure-as-a-Service (IaaS) that brings workflow-oriented, interoperable metabolomics data analysis platforms into the cloud. PhenoMeNal seamlessly integrates a wide array of existing open-source tools that are tested and packaged as Docker containers through the project's continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated, and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi, and Pachyderm.ConclusionsPhenoMeNal constitutes a keystone solution in cloud e-infrastructures available for metabolomics. PhenoMeNal is a unique and complete solution for setting up cloud e-infrastructures through easy-to-use web interfaces that can be scaled to any custom public and private cloud environment. By harmonizing and automating software installation and configuration and through ready-to-use scientific workflow user interfaces, PhenoMeNal has succeeded in providing scientists with workflow-driven, reproducible, and shareable metabolomics data analysis platforms that are interfaced through standard data formats, representative datasets, versioned, and have been tested for reproducibility and interoperability. The elastic implementation of PhenoMeNal further allows easy adaptation of the infrastructure to other application areas and ‘omics research domains.

Mass spectrometry technologies are widely used in the fields of ionomics and metabolomics to simultaneously profile the intracellular concentrations of, e.g., amino acids or elements in genome-wide mutant libraries. These molecular or sub-molecular features are generally non-Gaussian and their covariance reveals patterns of correlations that reflect the system nature of the cell biochemistry and biology. Here, we introduce two similarity measures, the Mahalanobis cosine and the hybrid Mahalanobis cosine, that enforce information from the empirical covariance matrix of omics data from high-throughput screening and that can be used to quantify similarities between the profiled features of different mutants. We evaluate the performance of these similarity measures in the task of inferring and integrating genetic networks from short-profile ionomics/metabolomics data through an analysis of experimental data sets related to the ionome and the metabolome of the model organism S. cerevisiae. The study of the resulting ionome–metabolome Saccharomyces cerevisiae multilayer genetic network, which encodes multiple omic-specific levels of correlations between genes, shows that the proposed measures can provide an alternative description of relations between biological processes when compared to the commonly used Pearson’s correlation coefficient and have the potential to guide the construction of novel hypotheses on the function of uncharacterised genes.

Background: Metabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism's metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological and many other applied biological domains. Its computationally-intensive nature has driven requirements for open data formats, data repositories and data analysis tools. However, the rapid progress has resulted in a mosaic of independent -and sometimes incompatible -analysis methods that are difficult to connect into a useful and complete data analysis solution. Findings: The PhenoMeNal (Phenome and Metabolome aNalysis) e-infrastructure provides a complete, workflow-oriented, interoperable metabolomics data analysis solution for a modern infrastructure-as-a-service (IaaS) cloud platform. PhenoMeNal seamlessly integrates a wide array of existing open source tools which are tested and packaged as Docker containers through the project's continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi and Pachyderm. Conclusions: PhenoMeNal constitutes a keystone solution in cloud infrastructures available for metabolomics. It provides scientists with a ready-to-use, workflow-driven, reproducible and shareable data analysis platform harmonizing the software installation and configuration through user-friendly web interfaces. The deployed cloud environments can be dynamically scaled to enable large-scale analyses which are interfaced through standard data formats, versioned, and have been tested for reproducibility and interoperability. The flexible implementation of PhenoMeNal allows easy adaptation of the infrastructure to other application areas and 'omics research domains.

Context Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is hence important to deeply characterise the human nutritional responses. Objective Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers. Methods We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) ten healthy, young, male individuals in response to two days of acute caloric restriction followed by refeeding, ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at four time points (0, 30, 60, 120 minutes), and iii) 200 random individuals from the Generation Scotland study. We compare the proteomic changes detected to metabolome data as well as endocrine parameters. Results Both acute nutritional interventions, caloric restriction and the glucose challenge, substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identify nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes. Conclusion Our study identifies APOC1 as a dominating nutritional responder in humans, and highlights the interdependency of acute nutritional response proteins and the endocrine system.