eXframe: reusable framework for storage, analysis and visualization of genomics experiments

<p>Abstract</p> <p>Background</p> <p>Genome-wide experiments are routinely conducted to measure gene expression, DNA-protein interactions and epigenetic status. Structured metadata for these experiments is imperative for a complete understanding of experimental conditions, to enable consistent data processing and to allow retrieval, comparison, and integration of experimental results. Even though several repositories have been developed for genomics data, only a few provide annotation of samples and assays using controlled vocabularies. Moreover, many of them are tailored for a single type of technology or measurement and do not support the integration of multiple data types.</p> <p>Results</p> <p>We have developed eXframe - a reusable web-based framework for genomics experiments that provides 1) the ability to publish structured data compliant with accepted standards 2) support for multiple data types including microarrays and next generation sequencing 3) query, analysis and visualization integration tools (enabled by consistent processing of the raw data and annotation of samples) and is available as open-source software. We present two case studies where this software is currently being used to build repositories of genomics experiments - one contains data from hematopoietic stem cells and another from Parkinson's disease patients.</p> <p>Conclusion</p> <p>The web-based framework eXframe offers structured annotation of experiments as well as uniform processing and storage of molecular data from microarray and next generation sequencing platforms. The framework allows users to query and integrate information across species, technologies, measurement types and experimental conditions. Our framework is reusable and freely modifiable - other groups or institutions can deploy their own custom web-based repositories based on this software. It is interoperable with the most important data formats in this domain. We hope that other groups will not only use eXframe, but also contribute their own useful modifications.</p

Pain Research Forum: application of scientific social media frameworks in neuroscience

Background: Social media has the potential to accelerate the pace of biomedical research through online collaboration, discussions, and faster sharing of information. Focused web-based scientific social collaboratories such as the Alzheimer Research Forum have been successful in engaging scientists in open discussions of the latest research and identifying gaps in knowledge. However, until recently, tools to rapidly create such communities and provide high-bandwidth information exchange between collaboratories in related fields did not exist. Methods: We have addressed this need by constructing a reusable framework to build online biomedical communities, based on Drupal, an open-source content management system. The framework incorporates elements of Semantic Web technology combined with social media. Here we present, as an exemplar of a web community built on our framework, the Pain Research Forum (PRF) (http://painresearchforum.org). PRF is a community of chronic pain researchers, established with the goal of fostering collaboration and communication among pain researchers. Results: Launched in 2011, PRF has over 1300 registered members with permission to submit content. It currently hosts over 150 topical news articles on research; more than 30 active or archived forum discussions and journal club features; a webinar series; an editor-curated weekly updated listing of relevant papers; and several other resources for the pain research community. All content is licensed for reuse under a Creative Commons license; the software is freely available. The framework was reused to develop other sites, notably the Multiple Sclerosis Discovery Forum (http://msdiscovery.org) and StemBook (http://stembook.org). Discussion: Web-based collaboratories are a crucial integrative tool supporting rapid information transmission and translation in several important research areas. In this article, we discuss the success factors, lessons learned, and ongoing challenges in using PRF as a driving force to develop tools for online collaboration in neuroscience. We also indicate ways these tools can be applied to other areas and uses

Genomic diversity affects the accuracy of bacterial single-nucleotide polymorphism-calling pipelines

Background: Accurately identifying SNPs from bacterial sequencing data is an essential requirement for using genomics to track transmission and predict important phenotypes such as antimicrobial resistance. However, most previous performance evaluations of SNP calling have been restricted to eukaryotic (human) data. Additionally, bacterial SNP calling requires choosing an appropriate reference genome to align reads to, which, together with the bioinformatic pipeline, affects the accuracy and completeness of a set of SNP calls obtained. This study evaluates the performance of 209 SNP calling pipelines using a combination of simulated data from 254 strains of 10 clinically common bacteria and real data from environmentally-sourced and genomically diverse isolates within the genera Citrobacter, Enterobacter, Escherichia and Klebsiella. Results: We evaluated the performance of 209 SNP calling pipelines, aligning reads to genomes of the same or a divergent strain. Irrespective of pipeline, a principal determinant of reliable SNP calling was reference genome selection. Across multiple taxa, there was a strong inverse relationship between pipeline sensitivity and precision, and the Mash distance (a proxy for average nucleotide divergence) between reads and reference genome. The effect was especially pronounced for diverse, recombinogenic, bacteria such as Escherichia coli, but less dominant for clonal species such as Mycobacterium tuberculosis. Conclusions: The accuracy of SNP calling for a given species is compromised by increasing intra-species diversity. When reads were aligned to the same genome from which they were sequenced, among the highest performing pipelines was Novoalign/GATK. By contrast, when reads were aligned to particularly divergent genomes, the highest-performing pipelines often employed the aligners NextGenMap or SMALT, and/or the variant callers LoFreq, mpileup or Strelka

Signatures of early frailty in the gut microbiota

Background: Frailty is arguably the biggest problem associated with population ageing, and associates with gut microbiome composition in elderly and care-dependent individuals. Here we characterize frailty associations with the gut microbiota in a younger community dwelling population, to identify targets for intervention to encourage healthy ageing. Method: We analysed 16S rRNA gene sequence data derived from faecal samples obtained from 728 female twins. Frailty was quantified using a frailty index (FI). Mixed effects models were used to identify associations with diversity, operational taxonomic units (OTUs) and taxa. OTU associations were replicated in the Eldermet cohort. Phenotypes were correlated with modules of OTUs collapsed by co-occurrence. Results: Frailty negatively associated with alpha diversity of the gut microbiota. Models considering a number of covariates identified 637 OTUs associated with FI. Twenty-two OTU associations were significant independent of alpha diversity. Species more abundant with frailty included Eubacterium dolichum and Eggerthella lenta. A Faecalibacterium prausnitzii OTU was less abundant in frailer individuals, and retained significance in discordant twin analysis. Sixty OTU associations were replicated in the Eldermet cohort. OTU co-occurrence modules had mutually exclusive associations between frailty and alpha diversity. Conclusions: There was a striking negative association between frailty and gut microbiota diversity, underpinned by specific taxonomic associations. Whether these relationships are causal or consequential is unknown. Nevertheless, they represent targets for diagnostic surveillance, or for intervention studies to improve vitality in ageing

Modeling the early phases of epidemics by Phakospora pachyrhizi in Brazilian soybean

Asian soybean rust, caused by the biotrophic basidiomycete Phakospora pachyrhizi, is a foliar disease that often causes considerable damage to soybean crops. The purpose of our work was to create a mechanistic model that can reliably represent epidemics of ASR in commercial soybean fields in Brazil. The most important inputs for the model are weather data (observations and forecast) and the initial observation of disease (or uredospore arrival). Our focus is on the first two or three cycles of infection after immigration into a soybean field. The model includes state variables for latent, infectious and senesced lesions, disease severity, uredospores, and soybean leaf area. Processes modeled include maturation through the latent and infectious periods, germination, sporulation, and processes affecting uredospores in the canopy. The model results were tested against field observations from trials at four locations in Brazil for the 2019/2020 growing season. The predictions generally matched the daily dynamics of disease progress in the field trials. The predictions reproduced the observed severity well with R2 value of 0.84. This high correlation indicates that our model is accurate enough to be used as a tool to predict the dynamics of ASR epidemics during the first few cycles after uredospore invasion into a soybean field. A sensitivity analysis was performed that showed that the model is sensitive to time and duration of the initial spore arrival. This indicates that spore traps or other observations should measure not only the first day of arrival but also subsequent days

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

​Residential mobility:Towards progress in mobility health research

Research into health disparities has long recognized the importance of residential mobility as a crucial factor in determining health outcomes. However, a lack of connectivity between the health and mobility literatures has led to a stagnation of theory and application on the health side, which lacks the detail and temporal perspectives now seen as critical to understanding residential mobility decisions. Through a critical re-think of mobility processes with respect to health outcomes and an exploitation of longitudinal analytical techniques, we argue that health geographers have the potential to better understand and identify the relationship that residential mobility has with health.“The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 615159 (ERC Consolidator Grant DEPRIVEDHOODS, Socio-spatial inequality, deprived neighbourhoods, and neighbourhood effects)”OLD Urban Renewal and Housin