Kristofer Wårell

The Proteios Software Environment: an extensible multiuser platform for management and analysis of proteomics data

Proteome analysis involves many steps that generate large quantities of data in different formats. This creates a need for automatic data merging and extraction of important features from data. Furthermore, metadata need to be collected and reported to enable critical evaluation of results. Many data analysis tools are developed locally in research laboratories and are nontrivial to adapt for other laboratories, preventing optimal exploitation of generated data. The proteomics field would benefit from user-friendly analysis and data management platforms in which method developers can make their analysis tools available for the community. Here, we describe the Proteios Software Environment (ProSE) that is built around a Web-based local data repository for proteomics experiments. The application features sample tracking, project sharing between multiple users, and automated data merging and analysis. ProSE has built-in support for several quantitative proteomics workflows, and integrates searching in several search engines, automated combination of the search results with predetermined false discovery rates, annotation of proteins and submission of results to public repositories. ProSE also provides a programming interface to enable local extensions, as well as database access using Web services. ProSE provides an analysis platform for proteomics research and is targeted for multiuser projects with needs to share data, sample tracking, and analysis result. ProSE is open source software available at http://www.proteios.org .

Omics Analyses Reveal a Potential Link between Hormone-Sensitive Lipase and Polyamine Metabolism.

Hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization from lipid stores, is expressed in the liver and decreased hepatic insulin sensitivity has been reported in our HSL null mouse model. Here, an integrated approach, comprising transcriptomics and proteomics together with targeted metabolite analysis, was used to investigate the liver phenotype of HSL null mice. Oligonucleotide microarray analysis revealed altered expression of genes involved in lipid and polyamine metabolism in HSL null mice compared with wild-type mice and in genes controlling the immune system in mice on high-fat diet versus mice on normal diet. Two-dimensional gel electrophoresis followed by MS and/or MS/MS allowed identification of 52 and 22 unique proteins differentially regulated according to the genotype and diet, respectively. Changes were observed mainly for proteins related to metabolism, including several proteins involved in polyamine metabolism or exhibiting methyl transferase activity. Despite the coordinated changes in mRNA and protein levels in polyamine pathways, no significant differences in levels of key polyamine metabolites were detected between the two genotypes. This study identifies a link between HSL and polyamine metabolism, which deserves further attention in view of the emerging data suggesting that disturbances in polyamine metabolism may affect insulin sensitivity. The present work also describes a limited correlation between mRNA, protein and metabolite levels, thus, underscoring the importance of integrated approaches.

Hunting for Protein Markers of Hypoxia by Combining Plasma Membrane Enrichment with a New Approach to Membrane Protein Analysis

Nontransient hypoxia is strongly associated with malignant lesions, resulting in aggressive behavior and resistance to treatment. We present an analysis of mRNA and protein expression changes in neuroblastoma cell lines occurring upon the transition from normoxia to hypoxia. The correlation between mRNA and protein level changes was poor, although some known hypoxia-driven genes and proteins correlated well. We present previously undescribed membrane proteins expressed under hypoxic conditions that are candidates for evaluation as biomarkers.