msmsEval: tandem mass spectral quality assignment for high-throughput proteomics

BACKGROUND: In proteomics experiments, database-search programs are the method of choice for protein identification from tandem mass spectra. As amino acid sequence databases grow however, computing resources required for these programs have become prohibitive, particularly in searches for modified proteins. Recently, methods to limit the number of spectra to be searched based on spectral quality have been proposed by different research groups, but rankings of spectral quality have thus far been based on arbitrary cut-off values. In this work, we develop a more readily interpretable spectral quality statistic by providing probability values for the likelihood that spectra will be identifiable. RESULTS: We describe an application, msmsEval, that builds on previous work by statistically modeling the spectral quality discriminant function using a Gaussian mixture model. This allows a researcher to filter spectra based on the probability that a spectrum will ultimately be identified by database searching. We show that spectra that are predicted by msmsEval to be of high quality, yet remain unidentified in standard database searches, are candidates for more intensive search strategies. Using a well studied public dataset we also show that a high proportion (83.9%) of the spectra predicted by msmsEval to be of high quality but that elude standard search strategies, are in fact interpretable. CONCLUSION: msmsEval will be useful for high-throughput proteomics projects and is freely available for download from . Supports Windows, Mac OS X and Linux/Unix operating systems

Development of Vortex Bioreactor Technology for Decentralised Water Treatment

The vortex bioreactor (VBR) is a simple decentralised water treatment system (DeWaTS) that sits at the interface between swirl flow, biotechnology and chemical engineering. The device utilises swirl flow and suspended activated beads to achieve downstream water processing and has been tested for applications including centrifugal-driven separation, pathogen neutralisation and metal absorption. The VBR was optimised for the treatment of faecally contaminated effluents in the developing world, and the design features related to the key challenges faced by the wastewater industry are highlighted here. The VBR has two aspects that can be modified to generate different reactor conditions: the impeller, where the swirl flow is modified through alterations of rotation speed, and impeller geometry and the suspended activated beads, which facilitate mixing and alter the reactor surface area. Data from testing for some of the different applications mentioned above are presented here, and future planned developments for the technology are discussed

Improved functional overview of protein complexes using inferred epistatic relationships

<p>Abstract</p> <p>Background</p> <p>Epistatic Miniarray Profiling(E-MAP) quantifies the net effect on growth rate of disrupting pairs of genes, often producing phenotypes that may be more (negative epistasis) or less (positive epistasis) severe than the phenotype predicted based on single gene disruptions. Epistatic interactions are important for understanding cell biology because they define relationships between individual genes, and between sets of genes involved in biochemical pathways and protein complexes. Each E-MAP screen quantifies the interactions between a logically selected subset of genes (e.g. genes whose products share a common function). Interactions that occur between genes involved in different cellular processes are not as frequently measured, yet these interactions are important for providing an overview of cellular organization.</p> <p>Results</p> <p>We introduce a method for combining overlapping E-MAP screens and inferring new interactions between them. We use this method to infer with high confidence 2,240 new strongly epistatic interactions and 34,469 weakly epistatic or neutral interactions. We show that accuracy of the predicted interactions approaches that of replicate experiments and that, like measured interactions, they are enriched for features such as shared biochemical pathways and knockout phenotypes. We constructed an expanded epistasis map for yeast cell protein complexes and show that our new interactions increase the evidence for previously proposed inter-complex connections, and predict many new links. We validated a number of these in the laboratory, including new interactions linking the SWR-C chromatin modifying complex and the nuclear transport apparatus.</p> <p>Conclusion</p> <p>Overall, our data support a modular model of yeast cell protein network organization and show how prediction methods can considerably extend the information that can be extracted from overlapping E-MAP screens.</p

Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome

BackgroundWe describe a severe form of congenital myasthenic syndrome (CMS) associated with congenital nephrosis and ocular malformations caused by two truncating mutations in the gene encoding the laminin beta2 subunit (LAMB2).Methods and resultsMutational analysis in the affected patient, who has a history of a serious untoward reaction to treatment with acetylcholinesterase inhibition, revealed two frame-shifting heteroallelic mutations, a maternally inherited 1478delG and a paternally inherited 4804delC. An anconeus muscle biopsy demonstrated a profound distortion of the architecture and function of the neuromuscular junction, which was strikingly similar to that seen in mice lacking laminin beta2 subunit. The findings included: pronounced reduction of the axon terminal size with encasement of the nerve endings by Schwann cells, severe widening of the primary synaptic cleft and invasion of the synaptic space by the processes of Schwann cells, and moderate simplification of postsynaptic folds and intact expression of the endplate acetylcholinesterase. The endplate potential quantal content was notably reduced, while the frequencies and amplitudes of miniature endplate potentials were only moderately diminished and the decay phases of miniature endplate potentials were normal. Western blot analysis of muscle and kidney tissue and immunohistochemistry of kidney tissue showed no laminin beta2 expression.ConclusionThis case, which represents a new type of synaptic CMS, exemplifies the wide variability of phenotypes associated with LAMB2 mutations and underscores the fundamental role that laminin beta2 plays in the development of the human neuromuscular junction

The efficacy of an extraoral scavenging device on reduction of splatter contamination during dental aerosol generating procedures: an exploratory study

Correction to: The efficacy of an extraoral scavenging device on reduction of splatter contamination during dental aerosol generating procedures: an exploratory study. Br Dent J (2020). https://doi.org/10.1038/s41415-020-2288-

Epistatic relationships reveal the functional organization of yeast transcription factors

A comprehensive quantitative genetic interaction map, or E-MAP, has provided a global view of the functional interdependencies between the components of the transcriptional apparatus in budding yeast.Transcription factors that display aggravating/negative genetic interactions regulate gene expression in an independent rather than coordinated manner.Parallel/compensating relationships between regulators often characterize transcriptional circuits

Patterns in Greater Sage-grouse population dynamics correspond with public grazing records at broad scales

Human land use, such as livestock grazing, can have profound yet varied effects on wildlife interacting within common ecosystems, yet our understanding of land-use effects is often generalized from short-term, local studies that may not correspond with trends at broader scales. Here we used public land records to characterize livestock grazing across Wyoming, USA, and we used Greater Sage-grouse (Centrocercus urophasianus) as a model organism to evaluate responses to livestock management. With annual counts of male Sage-grouse from 743 leks (breeding display sites) during 2004-2014, we modeled population trends in response to grazing level (represented by a relative grazing index) and timing across a gradient in vegetation productivity as measured by the Normalized Vegetation Difference Index (NDVI). We found grazing can have both positive and negative effects on Sage-grouse populations depending on the timing and level of grazing. Sage-grouse populations responded positively to higher grazing levels after peak vegetation productivity, but populations declined when similar grazing levels occurred earlier, likely reflecting the sensitivity of cool-season grasses to grazing during peak growth periods. We also found support for the hypothesis that effects of grazing management vary with local vegetation productivity. These results illustrate the importance of broad-scale analyses by revealing patterns in Sage-grouse population trends that may not be inferred from studies at finer scales, and could inform sustainable grazing management in these ecosystems