canEvolve: A Web Portal for Integrative Oncogenomics

Background & objective: Genome-wide profiles of tumors obtained using functional genomics platforms are being deposited to the public repositories at an astronomical scale, as a result of focused efforts by individual laboratories and large projects such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium. Consequently, there is an urgent need for reliable tools that integrate and interpret these data in light of current knowledge and disseminate results to biomedical researchers in a user-friendly manner. We have built the canEvolve web portal to meet this need. Results: canEvolve query functionalities are designed to fulfill most frequent analysis needs of cancer researchers with a view to generate novel hypotheses. canEvolve stores gene, microRNA (miRNA) and protein expression profiles, copy number alterations for multiple cancer types, and protein-protein interaction information. canEvolve allows querying of results of primary analysis, integrative analysis and network analysis of oncogenomics data. The querying for primary analysis includes differential gene and miRNA expression as well as changes in gene copy number measured with SNP microarrays. canEvolve provides results of integrative analysis of gene expression profiles with copy number alterations and with miRNA profiles as well as generalized integrative analysis using gene set enrichment analysis. The network analysis capability includes storage and visualization of gene co-expression, inferred gene regulatory networks and protein-protein interaction information. Finally, canEvolve provides correlations between gene expression and clinical outcomes in terms of univariate survival analysis. Conclusion: At present canEvolve provides different types of information extracted from 90 cancer genomics studies comprising of more than 10,000 patients. The presence of multiple data types, novel integrative analysis for identifying regulators of oncogenesis, network analysis and ability to query gene lists/pathways are distinctive features of canEvolve. canEvolve will facilitate integrative and meta-analysis of oncogenomics datasets

Distribution of selenium in the plume of the Gediz River, Izmir Bay, Aegean Sea

Selenium (Se) variations in the water column, suspended particulate matter, and sediment through the salinity gradient, together with water-quality parameters, were investigated over four different river conditions: lowest–highest runoff and high–low production period between November 2004 and August 2005 in the plume of the Gediz River, Aegean Sea, Turkey. The drainage basin of the Gediz delta is predominantly agricultural and industrial in character. Dissolved Se exceeded the water-quality standard of 5 μg L–1 during high flow and varied from 9.4 μg L–1 to 0.02 μg L–1 through the salinity gradient during the study period. Particulate Se ranged from 5.2 μg L–1 to 0.02 μg L–1. Sediment in the river mouth was highly affected by Se contamination and reached a level greater than four times (7.6 μg L–1 dry wt) the background level. The results indicated that Se supplied by the river was removed rapidly from the water column before the salinity reached an average value of about 20 and accumulated within the delta

γδ T cells affect IL-4 production and B-cell tolerance

γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4–producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4–regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4–inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance

Adapting temperature predictions to MR imaging in treatment position to improve simulation-guided hyperthermia for cervical cancer

Hyperthermia treatment consists of elevating the temperature of the tumor to increase the effectiveness of radiotherapy and chemotherapy. Hyperthermia treatment planning (HTP) is an important tool to optimize treatment quality using pre-treatment temperature predictions. The accuracy of these predictions depends on modeling uncertainties such as tissue properties and positioning. In this study, we evaluated if HTP accuracy improves when the patient is imaged inside the applicator at the start of treatment. Because perfusion is a major uncertainty source, the importance of accurate treatment position and anatomy was evaluated using different perfusion values. Volunteers were scanned using MR imaging without (&amp;#x201C;planning setup&amp;#x201D;) and with the MR-compatible hyperthermia device (&amp;#x201C;treatment setup&amp;#x201D;). Temperature-based quality indicators were used to assess the differences between the standard, apparent and the optimized hyperthermia dose. We conclude that pre-treatment imaging can improve HTP predictions accuracy but also, that tissue perfusion modelling is crucial if temperature-based optimization is applied.</p