Khalili, B. | Search bioRxiv

bioRxiv2018

PhenoMeNal: Processing and analysis of Metabolomics data in the Cloud

BackgroundMetabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organisms 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.\n\nFindingsThe 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 projects 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.\n\nConclusionsPhenoMeNal 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.

bioinformatics↗

bioRxiv2017

Feedback inhibition of Ras activity coordinates cell fusion with cell-cell contact

In fission yeast Schizosaccharomyces pombe, pheromone signalling engages a GPCR-Ras-MAPK cascade to trigger sexual differentiation leading to gamete fusion. Cell-cell fusion necessitates local cell wall digestion, the location of which relies on an initially dynamic actin fusion focus that becomes stabilized upon local enrichment of the signalling cascade. We constructed a live-reporter of active Ras1 (Ras1-GTP), also functional in S. cerevisiae, which revealed Ras activity at polarity sites peaking on the fusion structure before fusion. Remarkably, constitutive Ras1 activation promoted fusion focus stabilization and fusion attempts irrespective of cell-cell pairing, leading to cell lysis. Ras1 activity is restricted by the GTPase activating protein (GAP) Gap1, itself recruited to sites of Ras1-GTP. While the GAP domain on its own does not suffice for this localization, its recruitment to Ras1-GTP sites is essential to block untimely fusion attempts. We conclude that negative feedback control of Ras activity restrains the MAPK signal and couples fusion with cell-cell engagement.

cell biology↗