Interspecies data mining to predict novel ING-protein interactions in human

YesFunding provided by the Open Access Authors Fund

Spatiotemporal integration of molecular and anatomical data in virtual reality using semantic mapping

We have developed a computational framework for spatiotemporal integration of molecular and anatomical datasets in a virtual reality environment. Using two case studies involving gene expression data and pharmacokinetic data, respectively, we demonstrate how existing knowledge bases for molecular data can be semantically mapped onto a standardized anatomical context of human body. Our data mapping methodology uses ontological representations of heterogeneous biomedical datasets and an ontology reasoner to create complex semantic descriptions of biomedical processes. This framework provides a means to systematically combine an increasing amount of biomedical imaging and numerical data into spatiotemporally coherent graphical representations. Our work enables medical researchers with different expertise to simulate complex phenomena visually and to develop insights through the use of shared data, thus paving the way for pathological inference, developmental pattern discovery and biomedical hypothesis testing

Seahawk: moving beyond HTML in Web-based bioinformatics analysis

<p>Abstract</p> <p>Background</p> <p>Traditional HTML interfaces for input to and output from Bioinformatics analysis on the Web are highly variable in style, content and data formats. Combining multiple analyses can therfore be an onerous task for biologists. Semantic Web Services allow automated discovery of conceptual links between remote data analysis servers. A shared data ontology and service discovery/execution framework is particularly attractive in Bioinformatics, where data and services are often both disparate and distributed. Instead of biologists copying, pasting and reformatting data between various Web sites, Semantic Web Service protocols such as MOBY-S hold out the promise of seamlessly integrating multi-step analysis.</p> <p>Results</p> <p>We have developed a program (Seahawk) that allows biologists to intuitively and seamlessly chain together Web Services using a data-centric, rather than the customary service-centric approach. The approach is illustrated with a ferredoxin mutation analysis. Seahawk concentrates on lowering entry barriers for biologists: no prior knowledge of the data ontology, or relevant services is required. In stark contrast to other MOBY-S clients, in Seahawk users simply load Web pages and text files they already work with. Underlying the familiar Web-browser interaction is an XML data engine based on extensible XSLT style sheets, regular expressions, and XPath statements which import existing user data into the MOBY-S format.</p> <p>Conclusion</p> <p>As an easily accessible applet, Seahawk moves beyond standard Web browser interaction, providing mechanisms for the biologist to concentrate on the analytical task rather than on the technical details of data formats and Web forms. As the MOBY-S protocol nears a 1.0 specification, we expect more biologists to adopt these new semantic-oriented ways of doing Web-based analysis, which empower them to do more complicated, <it>ad hoc </it>analysis workflow creation without the assistance of a programmer.</p

Growth and weight status in treatment-naïve 12-16 year old adolescents with Alcohol Use Disorders in Cape Town, South Africa

The original publication is available at http://www.nutritionj.com/Publication of this article was funded by the Stellenbosch University Open Access Fund.Abstract: Background Heavy alcohol consumption during adolescence has many known harmful health and social consequences and is strongly associated with numerous health risk behaviours. The consequences of heavy alcohol use during adolescence on nutritional status, specifically growth and weight status are largely unknown at this time. Methods Substance use, anthropometric indices of growth and weight, dietary energy intake and physical activity in heavy drinking adolescents (meeting DSM-IV criteria for alcohol use disorders) and matched light/non-drinking control adolescents were assessed. Results Lifetime alcohol dose, measured in standard drinks of alcohol, was orders of magnitude higher in adolescents with alcohol use disorders (AUDs) compared to controls. The AUDs group was selected to represent relatively 'pure' AUDs, with minimal other drug use and no psychiatric diagnoses. The growth and weight status of adolescents with AUDs were generally comparable to that of controls, and is in line with the growth and weight status of the South African adolescent population. A greater proportion of overweight/obese females was found in both groups, with this percentage tending to be greater, although not significantly so, in the AUDs group. Adolescent females with AUDs had increased odds of being overweight/obese compared to controls, after adjustment for smoking, physical activity and energy intake. Conclusion Anthropometric indices of growth and weight status of participants in the Control and AUD groups were generally comparable. Female adolescents with AUDs may have an increased risk of being overweight/obese compared to adolescent females without AUDs. The presence of an AUD in our adolescent sample was associated with higher energy intake. Longitudinal studies are needed to elucidate the effects of heavy alcohol use on energy balance, growth and weight status in adolescents as they age. Nonetheless, the current study contributes to our understanding of the impacts of heavy alcohol consumption on important aspects of adolescent development.Publishers' versio

The 2nd DBCLS BioHackathon: interoperable bioinformatics Web services for integrated applications

<p>Abstract</p> <p>Background</p> <p>The interaction between biological researchers and the bioinformatics tools they use is still hampered by incomplete interoperability between such tools. To ensure interoperability initiatives are effectively deployed, end-user applications need to be aware of, and support, best practices and standards. Here, we report on an initiative in which software developers and genome biologists came together to explore and raise awareness of these issues: BioHackathon 2009.</p> <p>Results</p> <p>Developers in attendance came from diverse backgrounds, with experts in Web services, workflow tools, text mining and visualization. Genome biologists provided expertise and exemplar data from the domains of sequence and pathway analysis and glyco-informatics. One goal of the meeting was to evaluate the ability to address real world use cases in these domains using the tools that the developers represented. This resulted in i) a workflow to annotate 100,000 sequences from an invertebrate species; ii) an integrated system for analysis of the transcription factor binding sites (TFBSs) enriched based on differential gene expression data obtained from a microarray experiment; iii) a workflow to enumerate putative physical protein interactions among enzymes in a metabolic pathway using protein structure data; iv) a workflow to analyze glyco-gene-related diseases by searching for human homologs of glyco-genes in other species, such as fruit flies, and retrieving their phenotype-annotated SNPs.</p> <p>Conclusions</p> <p>Beyond deriving prototype solutions for each use-case, a second major purpose of the BioHackathon was to highlight areas of insufficiency. We discuss the issues raised by our exploration of the problem/solution space, concluding that there are still problems with the way Web services are modeled and annotated, including: i) the absence of several useful data or analysis functions in the Web service "space"; ii) the lack of documentation of methods; iii) lack of compliance with the SOAP/WSDL specification among and between various programming-language libraries; and iv) incompatibility between various bioinformatics data formats. Although it was still difficult to solve real world problems posed to the developers by the biological researchers in attendance because of these problems, we note the promise of addressing these issues within a semantic framework.</p

Study Protocol – Improving Access to Kidney Transplants (IMPAKT): A detailed account of a qualitative study investigating barriers to transplant for Australian Indigenous people with end-stage kidney disease

<p>Abstract</p> <p>Background</p> <p>Indigenous Australians are slightly more than 2% of the total Australian population however, in recent years they have comprised between 6 and 10% of new patients beginning treatment for end-stage kidney disease (ESKD). Although transplant is considered the optimal form of treatment for many ESKD patients there is a pronounced disparity between the rates at which Indigenous ESKD patients receive transplants compared with their non-Indigenous counterparts. The IMPAKT (Improving Access to Kidney Transplants) Interview study investigated reasons for this disparity through a large scale, in-depth interview study involving patients, nephrologists and key decision-making staff at selected Australian transplant and dialysis sites.</p> <p>Methods</p> <p>The design and conduct of the study reflected the multi-disciplinary membership of the core IMPAKT team. Promoting a participatory ethos, IMPAKT established partnerships with a network of hospital transplant units and hospital dialysis treatment centres that provide treatment to the vast majority of Indigenous patients across Australia. Under their auspices, the IMPAKT team conducted in-depth interviews in 26 treatment/service centres located in metropolitan, regional and remote Australia. Peer interviewing supported the engagement of Indigenous patients (146), and nephrologists (19). In total IMPAKT spoke with Indigenous and non-Indigenous patients (241), key renal nursing and other (non-specialist) staff (95) and a small number of relevant others (28). Data analysis was supported by QSR software. At each site, IMPAKT also documented educational programs and resources, mapped an hypothetical ‘patient journey’ to transplant through the local system and observed patient care and treatment routines.</p> <p>Discussion</p> <p>The national scope, inter-disciplinary approach and use of qualitative methods in an investigation of a significant health inequality affecting Indigenous people is, we believe, an Australian first. An exceptionally large cohort of Indigenous participants provided evaluative comment on their health services in relation to dialysis and transplant. Additionally, the data includes extensive parallel commentary from a cohort of specialists, nurses and other staff. The study considers a ‘patient journey’ to transplant within a diverse range of Australian treatment centre/workplace settings. The IMPAKT Interview study protocol may contribute to improvements in multi-disciplinary, flexible design health services research with hard to reach or vulnerable populations in Australia and elsewhere.</p

The 3rd DBCLS BioHackathon: improving life science data integration with Semantic Web technologies.

BACKGROUND: BioHackathon 2010 was the third in a series of meetings hosted by the Database Center for Life Sciences (DBCLS) in Tokyo, Japan. The overall goal of the BioHackathon series is to improve the quality and accessibility of life science research data on the Web by bringing together representatives from public databases, analytical tool providers, and cyber-infrastructure researchers to jointly tackle important challenges in the area of in silico biological research. RESULTS: The theme of BioHackathon 2010 was the 'Semantic Web', and all attendees gathered with the shared goal of producing Semantic Web data from their respective resources, and/or consuming or interacting those data using their tools and interfaces. We discussed on topics including guidelines for designing semantic data and interoperability of resources. We consequently developed tools and clients for analysis and visualization. CONCLUSION: We provide a meeting report from BioHackathon 2010, in which we describe the discussions, decisions, and breakthroughs made as we moved towards compliance with Semantic Web technologies - from source provider, through middleware, to the end-consumer.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The DBCLS BioHackathon: standardization and interoperability for bioinformatics web services and workflows. The DBCLS BioHackathon Consortium*

Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies

Estradiol Regulates Expression of Estrogen Receptor ERα46 in Human Macrophages

BACKGROUND:Monocytes and macrophages are key innate immune effector cells that produce cytokines and chemokines upon activation. We and others have shown that 17beta-estradiol (E2) has a direct role in the modulation of monocyte and macrophage immune function. However, relatively little is known about the ability of E2 to regulate isoform expression of estrogen receptors (ERs) in these cells. METHODOLOGY/PRINCIPAL FINDINGS:In this study, we quantify expression of ERalpha and ERbeta in human monocytes and macrophages. We also show for the first time that the N-terminal truncated ERalpha variant, ERalpha46, is expressed in both cell types. Promoter utilization studies reveal that transcription of ERalpha in both cell types occurs from upstream promoters E and F. Treatment with E2 induces ERalpha expression in macrophages but has no effect on ERbeta levels in either cell type. During monocyte-to-macrophage differentiation, ERalpha is upregulated in a time-dependent manner. Previous studies by our group demonstrated that E2 treatment attenuates production of the chemokine CXCL8 in an ER-dependent manner. We now show that ERalpha expression levels parallel the ability of E2 to suppress CXCL8 production. CONCLUSIONS/SIGNIFICANCE:This work demonstrates for the first time that human macrophages predominantly express the truncated ER variant ERalphap46, which is estradiol-inducible. This is mediated through usage of the ERalpha F promoter. Alternative promoter usage may account for tissue and cell type-specific differences in estradiol-induced effects on gene expression. These studies signify the importance of ERalpha expression and regulation in the ability of E2 to modulate innate immune responses