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Clinical metagenomics.
Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health
Steps in Metagenomics: Let’s Avoid Garbage in and Garbage Out
Is metagenomics a revolution or a new fad? Metagenomics is tightly associated with the availability of next-generation sequencing in all its implementations. The key feature of these new technologies, moving beyond the Sanger-based DNA sequencing approach, is the depth of nucleotide sequencing per sample.1 Knowing much more about a sample changes the traditional paradigms of “What is the most abundant?” or “What is the most significant?” to “What is present and potentially sigÂnificant that might influence the situation and outcome?” Let’s take the case of identifying proper biomarkers of disease state in the context of chronic disease prevention. Prevention has been deemed as a viable option to avert human chronic diseases and to curb healthÂcare management costs.2 The actual implementation of any effective preventive measures has proven to be rather difficult. In addition to the typically poor compliance of the general public, the vagueness of the successful validation of habit modification on the long-term risk, points to the need of defining new biomarkers of disease state. Scientists and the public are accepting the fact that humans are super-organisms, harboring both a human genome and a microbial genome, the latter being much bigger in size and diversity, and key for the health of individuals.3,4 It is time to investigate the intricate relationship between humans and their associated microbiota and how this relationship modÂulates or affects both partners.5 These remarks can be expanded to the animal and plant kingdoms, and holistically to the Earth’s biome. By its nature, the evolution and function of all the Earth’s biomes are influenced by a myriad of interactions between and among microbes (planktonic, in biofilms or host associated) and the surrounding physical environment.
The general definition of metagenomics is the cultivation-indepenÂdent analysis of the genetic information of the collective genomes of the microbes within a given environment based on its sampling. It focuses on the collection of genetic information through sequencing that can target DNA, RNA, or both. The subsequent analyses can be solely foÂcused on sequence conservation, phylogenetic, phylogenomic, function, or genetic diversity representation including yet-to-be annotated genes. The diversity of hypotheses, questions, and goals to be accomplished is endless. The primary design is based on the nature of the material to be analyzed and its primary function
DyVOSE project: experiences in applying privilege management infrastructures
Privilege Management Infrastructures (PMI) are emerging as a necessary alternative to authorization through Access Control Lists (ACL) as the need for finer grained security on the Grid increases in numerous domains. The 2-year JISC funded DyVOSE Project has investigated applying PMIs within an e-Science education context. This has involved establishing a Grid Computing module as part of Glasgow University’s Advanced MSc degree in Computing Science. A laboratory infrastructure was built for the students realising a PMI with the PERMIS software, to protect Grid Services they created. The first year of the course centered on building a static PMI at Glasgow. The second year extended this to allow dynamic attribute delegation between Glasgow and Edinburgh to support dynamic establishment of fine grained authorization based virtual organizations across multiple institutions. This dynamic delegation was implemented using the DIS (Delegation Issuing) Web Service supplied by the University of Kent. This paper describes the experiences and lessons learned from setting up and applying the advanced Grid authorization infrastructure within the Grid Computing course, focusing primarily on the second year and the dynamic virtual organisation setup between Glasgow and Edinburgh
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