GIVE: portable genome browsers for personal websites.

Growing popularity and diversity of genomic data demand portable and versatile genome browsers. Here, we present an open source programming library called GIVE that facilitates the creation of personalized genome browsers without requiring a system administrator. By inserting HTML tags, one can add to a personal webpage interactive visualization of multiple types of genomics data, including genome annotation, "linear" quantitative data, and genome interaction data. GIVE includes a graphical interface called HUG (HTML Universal Generator) that automatically generates HTML code for displaying user chosen data, which can be copy-pasted into user's personal website or saved and shared with collaborators. GIVE is available at: https://www.givengine.org/

Efficient counting of k-mers in DNA sequences using a bloom filter

<p>Abstract</p> <p>Background</p> <p>Counting <it>k</it>-mers (substrings of length <it>k </it>in DNA sequence data) is an essential component of many methods in bioinformatics, including for genome and transcriptome assembly, for metagenomic sequencing, and for error correction of sequence reads. Although simple in principle, counting <it>k</it>-mers in large modern sequence data sets can easily overwhelm the memory capacity of standard computers. In current data sets, a large fraction-often more than 50%-of the storage capacity may be spent on storing <it>k</it>-mers that contain sequencing errors and which are typically observed only a single time in the data. These singleton <it>k</it>-mers are uninformative for many algorithms without some kind of error correction.</p> <p>Results</p> <p>We present a new method that identifies all the <it>k</it>-mers that occur more than once in a DNA sequence data set. Our method does this using a Bloom filter, a probabilistic data structure that stores all the observed <it>k</it>-mers implicitly in memory with greatly reduced memory requirements. We then make a second sweep through the data to provide exact counts of all nonunique <it>k</it>-mers. For example data sets, we report up to 50% savings in memory usage compared to current software, with modest costs in computational speed. This approach may reduce memory requirements for any algorithm that starts by counting <it>k</it>-mers in sequence data with errors.</p> <p>Conclusions</p> <p>A reference implementation for this methodology, BFCounter, is written in C++ and is GPL licensed. It is available for free download at <url>http://pritch.bsd.uchicago.edu/bfcounter.html</url></p

Differential analysis for high density tiling microarray data

<p>Abstract</p> <p>Background</p> <p>High density oligonucleotide tiling arrays are an effective and powerful platform for conducting unbiased genome-wide studies. The <it>ab initio </it>probe selection method employed in tiling arrays is unbiased, and thus ensures consistent sampling across coding and non-coding regions of the genome. These arrays are being increasingly used to study the associated processes of transcription, transcription factor binding, chromatin structure and their association. Studies of differential expression and/or regulation provide critical insight into the mechanics of transcription and regulation that occurs during the developmental program of a cell. The time-course experiment, which comprises an <it>in-vivo </it>system and the proposed analyses, is used to determine if annotated and un-annotated portions of genome manifest coordinated differential response to the induced developmental program.</p> <p>Results</p> <p>We have proposed a novel approach, based on a piece-wise function – to analyze genome-wide differential response. This enables segmentation of the response based on protein-coding and non-coding regions; for genes the methodology also partitions differential response with a 5' versus 3' versus intra-genic bias.</p> <p>Conclusion</p> <p>The algorithm built upon the framework of Significance Analysis of Microarrays, uses a generalized logic to define regions/patterns of coordinated differential change. By not adhering to the gene-centric paradigm, discordant differential expression patterns between exons and introns have been identified at a FDR of less than 12 percent. A co-localization of differential binding between RNA Polymerase II and tetra-acetylated histone has been quantified at a p-value < 0.003; it is most significant at the 5' end of genes, at a p-value < 10^-13. The prototype R code has been made available as supplementary material [see Additional file <supplr sid="S1">1</supplr>].</p> <suppl id="S1"> <title> <p>Additional file 1</p> </title> <text> <p>gsam_prototypercode.zip. File archive comprising of prototype R code for gSAM implementation including readme and examples.</p> </text> <file name="1471-2105-8-359-S1.zip"> <p>Click here for file</p> </file> </suppl

Community views about routine HIV testing and antiretroviral treatment in Botswana: signs of progress from a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The Botswana government began providing free antiretroviral therapy (ART) in 2002 and in 2004 introduced routine HIV testing (RHT) in government health facilities, aiming to increase HIV testing and uptake of ART. There have been concerns that the RHT programme might be coercive, lead to increased partner violence, and drive people away from government health services.</p> <p>Methods</p> <p>We conducted a household survey of 1536 people in a stratified random sample of communities across Botswana, asking about use and experience of government health services, views about RHT, views about ART, and testing for HIV in the last 12 months. Focus groups further discussed issues about ART.</p> <p>Results</p> <p>Some 81% of respondents had visited a government clinic within the last 24 months. Of these 92% were satisfied with the service, 96% felt they were treated with respect and 90% were comfortable about confidentiality. Almost all respondents said they would choose a government clinic for treatment of AIDS.</p> <p>Nearly one half (47%) thought they were at risk of HIV. Those who had experienced partner violence within the last 12 months were more likely to think themselves at risk. One half of those who had visited a government facility in the last 24 months were offered HIV tests, and nearly half were tested. A few (8%) of those who were not asked thought they were tested. Most people (79%) had heard of RHT and 94% were in favour of it. Over one half (55%) of the entire sample had been tested for HIV within the last 12 months, one half of these through RHT. Women were more likely to have been tested.</p> <p>Nearly everyone (94%) had heard of ART and thought it could help AIDS. Focus groups identified problems of access to ART due to distance from treatment centres and long queues in the centres.</p> <p>Conclusion</p> <p>Public awareness and approval of RHT was very high. The high rate of RHT has contributed to the overall high rate of HIV testing. The government's programme to increase HIV testing and uptake of ART is apparently working well. However, turning the tide of the epidemic will also require further concerted efforts to reduce the rate of new HIV infections.</p

The Patient Deficit Model Overturned: a qualitative study of patients' perceptions of invitation to participate in a randomized controlled trial comparing selective bladder preservation against surgery in muscle invasive bladder cancer (SPARE, CRUK/07/011)

BACKGROUND: Evidence suggests that poor recruitment into clinical trials rests on a patient ‘deficit’ model – an inability to comprehend trial processes. Poor communication has also been cited as a possible barrier to recruitment. A qualitative patient interview study was included within the feasibility stage of a phase III non-inferiority Randomized Controlled Trial (RCT) (SPARE, CRUK/07/011) in muscle invasive bladder cancer. The aim was to illuminate problems in the context of randomization. METHODS: The qualitative study used a ‘Framework Analysis’ that included ‘constant comparison’ in which semi-structured interviews are transcribed, analyzed, compared and contrasted both between and within transcripts. Three researchers coded and interpreted data. RESULTS: Twenty-four patients agreed to enter the interview study; 10 decliners of randomization and 14 accepters, of whom 2 subsequently declined their allocated treatment. The main theme applying to the majority of the sample was confusion and ambiguity. There was little indication that confusion directly impacted on decisions to enter the SPARE trial. However, confusion did appear to impact on ethical considerations surrounding ‘informed consent’, as well as cause a sense of alienation between patients and health personnel. Sub-optimal communication in many guises accounted for the confusion, together with the logistical elements of a trial that involved treatment options delivered in a number of geographical locations. CONCLUSIONS: These data highlight the difficulty of providing balanced and clear trial information within the UK health system, despite best intentions. Involvement of multiple professionals can impact on communication processes with patients who are considering participation in RCTs. Our results led us to question the ‘deficit’ model of patient behavior. It is suggested that health professionals might consider facilitating a context in which patients feel fully included in the trial enterprise and potentially consider alternatives to randomization where complex interventions are being tested. TRIAL REGISTRATION: ISRCTN6112646

Diabetes self-management arrangements in Europe: a realist review to facilitate a project implemented in six countries

Background: Self-management of long term conditions can promote quality of life whilst delivering benefits to the financing of health care systems. However, rarely are the meso-level influences, likely to be of direct relevance to these desired outcomes, systematically explored. No specific international guidelines exist suggesting the features of the most appropriate structure and organisation of health care systems within which to situate self-management approaches and practices. This review aimed to identify the quantitative literature with regard to diabetes self-management arrangements currently in place within the health care systems of six countries (The United Kingdom, The Netherlands, Norway, Spain, Bulgaria, and Greece) and explore how these are integrated into the broader health care and welfare systems in each country. Methods: The methodology for a realist review was followed. Publications of interest dating from 2000 to 2013 were identified through appropriate MeSH terms by a systematic search in six bibliographic databases. A search diary was maintained and the studies were assessed for their quality and risk of bias. Results: Following the multi-step search strategy, 56 studies were included in the final review (the majority from the UK) reporting design methods and findings on 21 interventions and programmes for diabetes and chronic disease self-management. Most (11/21, 52%) of the interventions were designed to fit within the context of primary care. The majority (11/21, 52%) highlighted behavioural change as an important goal. Finally, some (5/21, 24%) referred explicitly to Internet-based tools. Conclusions: This review is based on results which are derived from a total of at least 5,500 individuals residing in the six participating countries. It indicates a policy shift towards patient-centred self-management of diabetes in a primary care context. The professional role of diabetes specialist nurses, the need for multidisciplinary approaches and a focus on patient education emerge as fundamental principles in the design of relevant programmes. Socio-economic circumstances are relevant to the capacity to self-manage and suggest that any gains and progress will be hard to maintain during economic austerity. This realist review should be interpreted within the wider context of a whole systems approach regarding self-care support and chronic illness management

Structural Basis for Type VI Secretion Effector Recognition by a Cognate Immunity Protein

The type VI secretion system (T6SS) has emerged as an important mediator of interbacterial interactions. A T6SS from Pseudomonas aeruginosa targets at least three effector proteins, type VI secretion exported 1–3 (Tse1–3), to recipient Gram-negative cells. The Tse2 protein is a cytoplasmic effector that acts as a potent inhibitor of target cell proliferation, thus providing a pronounced fitness advantage for P. aeruginosa donor cells. P. aeruginosa utilizes a dedicated immunity protein, type VI secretion immunity 2 (Tsi2), to protect against endogenous and intercellularly-transferred Tse2. Here we show that Tse2 delivered by the T6SS efficiently induces quiescence, not death, within recipient cells. We demonstrate that despite direct interaction of Tsi2 and Tse2 in the cytoplasm, Tsi2 is dispensable for targeting the toxin to the secretory apparatus. To gain insights into the molecular basis of Tse2 immunity, we solved the 1.00 Å X-ray crystal structure of Tsi2. The structure shows that Tsi2 assembles as a dimer that does not resemble previously characterized immunity or antitoxin proteins. A genetic screen for Tsi2 mutants deficient in Tse2 interaction revealed an acidic patch distal to the Tsi2 homodimer interface that mediates toxin interaction and immunity. Consistent with this finding, we observed that destabilization of the Tsi2 dimer does not impact Tse2 interaction. The molecular insights into Tsi2 structure and function garnered from this study shed light on the mechanisms of T6 effector secretion, and indicate that the Tse2–Tsi2 effector–immunity pair has features distinguishing it from previously characterized toxin–immunity and toxin–antitoxin systems