34 research outputs found

    Comparative genomics of the major parasitic worms

    Get PDF
    Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms

    Gene Ontology annotations and resources.

    Get PDF
    The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources

    The genome of Onchocerca volvulus, agent of river blindness

    Get PDF
    Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development

    Profiling the mental health of diabetic patients: a cross-sectional survey of Zimbabwean patients

    Get PDF
    Objective The burden of diabetes mellitus has exponentially increased in low resource settings. Patients with diabetes are more likely to exhibit poor mental health which negatively affects treatment outcomes. However, patients with high levels of social support (SS) are likely to report optimal mental health. We sought to determine how SS affects the report of psychiatric morbidity and health-related quality of life (HRQoL) in 108 diabetic patients in Harare, Zimbabwe. Results The average age of participants was 54.1 (SD 18.6) years. Most of the participants were; females (69.4%), married (51.9%), and were of low level of income (43.5%). 37.1% of the participants exhibited signs of psychiatric morbidity [mean Shona Symptoms Questionnaire score—6.7 (SD 3.2)]. Further, patients also reported lower HRQoL [mean EQ-5D-VAS score—64.1 (SD 15.3)] and high levels of SS [mean Multidimensional Scale of Perceived Social Support score—43.7 (SD 11.5)]. Patients who received greater amount of SS had optimal mental health. Being female, unmarried, lower education attainment, having more comorbid conditions, being diagnosed with type 2 diabetes and having been diagnosed of diabetes for a longer duration were associated with poorer mental health. It is important to develop context-specific interventions to improve diabetic patients’ mental health

    An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

    Get PDF
    Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

    An expanded evaluation of protein function prediction methods shows an improvement in accuracy

    Get PDF
    Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

    An expanded evaluation of protein function prediction methods shows an improvement in accuracy

    Get PDF
    Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging.Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2.Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

    Gene Ontology Consortium: going forward

    Get PDF
    The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology

    Prevalence of heart failure in Australia:A systematic review

    Get PDF
    Background: In the absence of a systematic collection of data pertaining to heart failure, summarizing the data available from individual studies provides an opportunity to estimate the burden of heart failure. The present study systematically reviewed the literature to estimate the incidence and prevalence rates of heart failure in Australia. Methods: Studies reporting on prevalence or incidence of heart failure published between 1990 and 2015 were identified through a systematic search of Embase, PubMed, Ovid Medline, MeSH, Scopus and websites of the Australian Institute of Health, and Welfare and Australian Bureau of Statistics. Results: The search yielded a total of 4978 records, of which thirteen met the inclusion criteria. There were no studies reporting on the incidence of heart failure. The prevalence of heart failure in the Australian population ranged between 1.0 % and 2.0 %, with a significant proportion of cases being previously undiagnosed. The burden of heart failure was higher among Indigenous than non-Indigenous Australians (age-standardized prevalence rate ratio of 1.7). Heart failure was prevalent in women than men, and in rural and remote regions than in the metropolitan and capital territories. Conclusion: This systematic review highlights the limited available data on the epidemiology of heart failure in Australia. Population level studies, using standardized approaches, are needed in order to precisely describe the burden of HF in the population
    corecore