interPopula: a Python API to access the HapMap Project dataset

<p>Abstract</p> <p>Background</p> <p>The HapMap project is a publicly available catalogue of common genetic variants that occur in humans, currently including several million SNPs across 1115 individuals spanning 11 different populations. This important database does not provide any programmatic access to the dataset, furthermore no standard relational database interface is provided.</p> <p>Results</p> <p>interPopula is a Python API to access the HapMap dataset. interPopula provides integration facilities with both the Python ecology of software (e.g. Biopython and matplotlib) and other relevant human population datasets (e.g. Ensembl gene annotation and UCSC Known Genes). A set of guidelines and code examples to address possible inconsistencies across heterogeneous data sources is also provided.</p> <p>Conclusions</p> <p>interPopula is a straightforward and flexible Python API that facilitates the construction of scripts and applications that require access to the HapMap dataset.</p

Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure

A versatile computational pipeline for bacterial genome annotation improvement and comparative analysis, with Brucella as a use case

We present a bacterial genome computational analysis pipeline, called GenVar. The pipeline, based on the program GeneWise, is designed to analyze an annotated genome and automatically identify missed gene calls and sequence variants such as genes with disrupted reading frames (split genes) and those with insertions and deletions (indels). For a given genome to be analyzed, GenVar relies on a database containing closely related genomes (such as other species or strains) as well as a few additional reference genomes. GenVar also helps identify gene disruptions probably caused by sequencing errors. We exemplify GenVar's capabilities by presenting results from the analysis of four Brucella genomes. Brucella is an important human pathogen and zoonotic agent. The analysis revealed hundreds of missed gene calls, new split genes and indels, several of which are species specific and hence provide valuable clues to the understanding of the genome basis of Brucella pathogenicity and host specificity

Proteomic Analysis of Human Skin Treated with Larval Schistosome Peptidases Reveals Distinct Invasion Strategies among Species of Blood Flukes

Schistosome parasites are a major cause of disease in the developing world, but the mechanism by which these parasites first infect their host has been studied at the molecular level only for S. mansoni. In this paper, we have mined recent genome annotations of S. mansoni and S. japonicum, a zoonotic schistosome species, to identify differential expansion of peptidase gene families that may be involved in parasite invasion and subsequent migration through skin. Having identified a serine peptidase gene family in S. mansoni and a cysteine peptidase gene family in S. japonicum, we then used a comparative proteomic approach to identify potential substrates of representative members of both classes of enzymes from S. mansoni in human skin. The results of this study suggest that while these species evolved to use different classes of peptidases in host invasion, both are capable of cleaving components of the epidermis and dermal extracellular matrix, as well as proteins involved in the host immune response against the migrating parasite

Trends and determinants of excess winter mortality in New Zealand: 1980 to 2000

<p>Abstract</p> <p>Background</p> <p>Although many countries experience an increase in mortality during winter, the magnitude of this increase varies considerably, suggesting that some winter excess may be avoidable. Conflicting evidence has been presented on the role of gender, region and deprivation. Little has been published on the magnitude of excess winter mortality (EWM) in New Zealand (NZ) and other Southern Hemisphere countries.</p> <p>Methods</p> <p>Monthly mortality rates per 100,000 population were calculated from routinely collected national mortality data for 1980 to 2000. Generalised negative binomial regression models were used to compare mortality rates between winter (June–September) and the warmer months (October–May).</p> <p>Results</p> <p>From 1980–2000 around 1600 excess winter deaths occurred each year with winter mortality rates 18% higher than expected from non-winter rates. Patterns of EWM by age group showed the young and the elderly to be particularly vulnerable. After adjusting for all major covariates, the winter:non-winter mortality rate ratio from 1996–2000 in females was 9% higher than in males. Mortality caused by diseases of the circulatory system accounted for 47% of all excess winter deaths from 1996–2000 with mortality from diseases of the respiratory system accounting for 31%. There was no evidence to suggest that patterns of EWM differed by ethnicity, region or local-area based deprivation level. No decline in seasonal mortality was evident over the two decades.</p> <p>Conclusion</p> <p>EWM in NZ is substantial and at the upper end of the range observed internationally. Interventions to reduce EWM are important, but the surprising lack of variation in EWM by ethnicity, region and deprivation, provides little guidance for how such mortality can be reduced.</p

ContDist: a tool for the analysis of quantitative gene and promoter properties

<p>Abstract</p> <p>Background</p> <p>The understanding of how promoter regions regulate gene expression is complicated and far from being fully understood. It is known that histones' regulation of DNA compactness, DNA methylation, transcription factor binding sites and CpG islands play a role in the transcriptional regulation of a gene. Many high-throughput techniques exist nowadays which permit the detection of epigenetic marks and regulatory elements in the promoter regions of thousands of genes. However, so far the subsequent analysis of such experiments (e.g. the resulting gene lists) have been hampered by the fact that currently no tool exists for a detailed analysis of the promoter regions.</p> <p>Results</p> <p>We present ContDist, a tool to statistically analyze quantitative gene and promoter properties. The software includes approximately 200 quantitative features of gene and promoter regions for 7 commonly studied species. In contrast to "traditionally" ontological analysis which only works on qualitative data, all the features in the underlying annotation database are quantitative gene and promoter properties.</p> <p>Utilizing the strong focus on the promoter region of this tool, we show its usefulness in two case studies; the first on differentially methylated promoters and the second on the fundamental differences between housekeeping and tissue specific genes. The two case studies allow both the confirmation of recent findings as well as revealing previously unreported biological relations.</p> <p>Conclusion</p> <p>ContDist is a new tool with two important properties: 1) it has a strong focus on the promoter region which is usually disregarded by virtually all ontology tools and 2) it uses quantitative (continuously distributed) features of the genes and its promoter regions which are not available in any other tool. ContDist is available from <url>http://web.bioinformatics.cicbiogune.es/CD/ContDistribution.php</url></p

Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence

Activation of the endothelin A receptor (ETA) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ETA may have anticancer effects, while retaining beneficial endothelin B receptor (ETB)-mediated effects such as apoptosis and clearance of ET-1. ZD4054 is an orally active, specific ETA antagonist in clinical development. In receptor-binding studies, ZD4054 specifically bound to ETA with high affinity; no binding was detected at ETB. In a randomised placebo-controlled trial in eight healthy volunteers, a single oral dose of ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion of ET-1, thus providing clinical evidence of ETA blockade. ETB blockade was assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers. For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h were within the placebo reference range (a rise in ET-1 would indicate ETB blockade) and there was no evidence of dose-related changes. These data confirm the specificity of ZD4054 for ETA, with no activity at ETB in a clinical or preclinical setting. As a result of this specificity, ZD4054 has the potential to block multiple ETA-induced pathological processes, while allowing beneficial ETB-mediated processes to continue, which may, in turn, lead to an effective cancer therapy

Facebook's Mobile Career

At the end of its first decade, Facebook’s identity, popularity, and characteristics are shaped in important ways by its becoming a form of mobile media, as much as it as platform associated with Internet and social media. This paper seeks to explore and understand Facebook as the important force in mobile media and communication it now is. It draws upon and combines perspectives from technology production, design, and economy, as well as user adoption, consumption, practices, affect, emotion, and resistance. The paper discusses the beginnings of mobile Facebook, and the early adoption of mobile Facebook associated with the rise of smartphones. The second part of the paper explores Facebook’s integration with photography (with Instagram) and social games (such as Zynga’s Farmville). The paper argues that Facebook’s mobile career is an accomplishment that has distinctively melded evolving affordances, everyday use across a wide range of settings, as well as political economies, corporate strategy, and design.Australian Research Counci

Ensembl 2008.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure