miRQuest: integration of tools on a Web server for microRNA research.

This report describes the miRQuest - a novel middleware available in a Web server that allows the end user to do the miRNA research in a user-friendly way. It is known that there are many prediction tools for microRNA (miRNA) identification that use different programming languages and methods to realize this task. It is difficult to understand each tool and apply it to diverse datasets and organisms available for miRNA analysis. miRQuest can easily be used by biologists and researchers with limited experience with bioinformatics. We built it using the middleware architecture on a Web platform for miRNA research that performs two main functions: i) integration of different miRNA prediction tools for miRNA identification in a user-friendly environment; and ii) comparison of these prediction tools. In both cases, the user provides sequences (in FASTA format) as an input set for the analysis and comparisons. All the tools were selected on the basis of a survey of the literature on the available tools for miRNA prediction. As results, three different cases of use of the tools are also described, where one is the miRNA identification analysis in 30 different species. Finally, miRQuest seems to be a novel and useful tool; and it is freely available for both benchmarking and miRNA identification at http://mirquest.integrativebioinformatics.me/.

Relation of pretreatment sequence diversity in NS5A region of HCV genotype 1 with immune response between pegylated-INF/ribavirin therapy outcomes.

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responses and the combination of pegylated interferon (INF)-α and ribavirin therapy. Major histocompatibility complex class I restricted CD8(+) T cells are responsible for the control of viraemia in HCV infection, and several studies suggest protection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated α-INF with ribavirin therapy and test evidence of natural selection on the virus in those who failed treatment, using five maximum likelihood evolutionary models from PAML package. The group of sustained virological responders showed three epitopes with frequencies higher than Non-responders group, all had statistical support, and we observed evidence of selection pressure in the last group. No escape mutation was observed. Interestingly, the epitope VLSDFKTWL was 100% conserved in SVR group. These results suggest that the response to treatment can be explained by the increase in immune pressure, induced by interferon therapy, and the presence of those epitopes may represent an important factor in determining the outcome of therapy.

Relation of pretreatment sequence diversity in NS5A region ofHCV genotype 1 with immune response between pegylated- INF/ribavirin therapy outcomes

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responsesand the combination of pegylated interferon (INF)-a and ribavirin therapy. Major histocompatibility complex class Irestricted CD8+ T cells are responsible for the control of viraemia in HCV infection, and several studies suggestprotection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated a-INF with ribavirin therapy and test evidence of natural.