Impact of genome assembly status on ChIP-Seq and ChIP-PET data mapping

<p>Abstract</p> <p>Background</p> <p>ChIP-Seq and ChIP-PET can potentially be used with any genome for genome wide profiling of protein-DNA interaction sites. Unfortunately, it is probable that most genome assemblies will never reach the quality of the human genome assembly. Therefore, it remains to be determined whether ChIP-Seq and ChIP-PET are practicable with genome sequences other than a few (<it>e.g</it>. human and mouse).</p> <p>Findings</p> <p>Here, we used <it>in silico </it>simulations to assess the impact of completeness or fragmentation of genome assemblies on ChIP-Seq and ChIP-PET data mapping.</p> <p>Conclusions</p> <p>Most currently published genome assemblies are suitable for mapping the short sequence tags produced by ChIP-Seq or ChIP-PET.</p

The road to deterministic matrices with the restricted isometry property

The restricted isometry property (RIP) is a well-known matrix condition that provides state-of-the-art reconstruction guarantees for compressed sensing. While random matrices are known to satisfy this property with high probability, deterministic constructions have found less success. In this paper, we consider various techniques for demonstrating RIP deterministically, some popular and some novel, and we evaluate their performance. In evaluating some techniques, we apply random matrix theory and inadvertently find a simple alternative proof that certain random matrices are RIP. Later, we propose a particular class of matrices as candidates for being RIP, namely, equiangular tight frames (ETFs). Using the known correspondence between real ETFs and strongly regular graphs, we investigate certain combinatorial implications of a real ETF being RIP. Specifically, we give probabilistic intuition for a new bound on the clique number of Paley graphs of prime order, and we conjecture that the corresponding ETFs are RIP in a manner similar to random matrices.Comment: 24 page

Unexpected Novel Relational Links Uncovered by Extensive Developmental Profiling of Nuclear Receptor Expression

Nuclear receptors (NRs) are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes) using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily

Rapid Implementation of an Integrated Large-Scale HIV Counseling and Testing, Malaria, and Diarrhea Prevention Campaign in Rural Kenya

BACKGROUND: Integrated disease prevention in low resource settings can increase coverage, equity and efficiency in controlling high burden infectious diseases. A public-private partnership with the Ministry of Health, CDC, Vestergaard Frandsen and CHF International implemented a one-week integrated multi-disease prevention campaign. METHOD: Residents of Lurambi, Western Kenya were eligible for participation. The aim was to offer services to at least 80% of those aged 15-49. 31 temporary sites in strategically dispersed locations offered: HIV counseling and testing, 60 male condoms, an insecticide-treated bednet, a household water filter for women or an individual filter for men, and for those testing positive, a 3-month supply of cotrimoxazole and referral for follow-up care and treatment. FINDINGS: Over 7 days, 47,311 people attended the campaign with a 96% uptake of the multi-disease preventive package. Of these, 99.7% were tested for HIV (87% in the target 15-49 age group); 80% had previously never tested. 4% of those tested were positive, 61% were women (5% of women and 3% of men), 6% had median CD4 counts of 541 cell/µL (IQR; 356, 754). 386 certified counselors attended to an average 17 participants per day, consistent with recommended national figures for mass campaigns. Among women, HIV infection varied by age, and was more likely with an ended marriage (e.g. widowed vs. never married, OR.3.91; 95% CI. 2.87-5.34), and lack of occupation. In men, quantitatively stronger relationships were found (e.g. widowed vs. never married, OR.7.0; 95% CI. 3.5-13.9). Always using condoms with a non-steady partner was more common among HIV-infected women participants who knew their status compared to those who did not (OR.5.4 95% CI. 2.3-12.8). CONCLUSION: Through integrated campaigns it is feasible to efficiently cover large proportions of eligible adults in rural underserved communities with multiple disease preventive services simultaneously achieving various national and international health development goals

Social and cultural efficacies of medicines: Complications for antiretroviral therapy

Using ethnographic examples of medicine use, prescription, distribution and production, the authors argue that social and cultural effects of pharmaceuticals should be taken into account. Non-medical effects deeply influence the medical outcome of medicine use. Complications around the advent of anti-AIDS medicines in poor countries are taken as a point in case. The authors are medical anthropologists specialised in the social and cultural analysis of pharmaceuticals

PlasmoDraft: a database of Plasmodium falciparum gene function predictions based on postgenomic data

<p>Abstract</p> <p>Background</p> <p>Of the 5 484 predicted proteins of <it>Plasmodium falciparum</it>, the main causative agent of malaria, about 60% do not have sufficient sequence similarity with proteins in other organisms to warrant provision of functional assignments. Non-homology methods are thus needed to obtain functional clues for these uncharacterized genes.</p> <p>Results</p> <p>We present PlasmoDraft <url>http://atgc.lirmm.fr/PlasmoDraft/</url>, a database of Gene Ontology (GO) annotation predictions for <it>P. falciparum </it>genes based on postgenomic data. Predictions of PlasmoDraft are achieved with a <it>Guilt By Association </it>method named Gonna. This involves (1) a predictor that proposes GO annotations for a gene based on the similarity of its profile (measured with transcriptome, proteome or interactome data) with genes already annotated by GeneDB; (2) a procedure that estimates the confidence of the predictions achieved with each data source; (3) a procedure that combines all data sources to provide a global summary and confidence estimate of the predictions. Gonna has been applied to all <it>P. falciparum </it>genes using most publicly available transcriptome, proteome and interactome data sources. Gonna provides predictions for numerous genes without any annotations. For example, 2 434 genes without any annotations in the Biological Process ontology are associated with specific GO terms (<it>e.g</it>. Rosetting, Antigenic variation), and among these, 841 have confidence values above 50%. In the Cellular Component and Molecular Function ontologies, 1 905 and 1 540 uncharacterized genes are associated with specific GO terms, respectively (740 and 329 with confidence value above 50%).</p> <p>Conclusion</p> <p>All predictions along with their confidence values have been compiled in PlasmoDraft, which thus provides an extensive database of GO annotation predictions that can be achieved with these data sources. The database can be accessed in different ways. A global view allows for a quick inspection of the GO terms that are predicted with high confidence, depending on the various data sources. A gene view and a GO term view allow for the search of potential GO terms attached to a given gene, and genes that potentially belong to a given GO term.</p

Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study

METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda.RESULTS: The prevalence of TDR is predicted to rise from 6.7$1612 to $2234 (IQR$450-dominated) per QALY gained.CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority.INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR

Communication in bacteria: an ecological and evolutionary perspective

Individual bacteria can alter their behaviour through chemical interactions between organisms in microbial communities - this is generally referred to as quorum sensing. Frequently, these interactions are interpreted in terms of communication to mediate coordinated, multicellular behaviour. We show that the nature of interactions through quorum-sensing chemicals does not simply involve cooperative signals, but entails other interactions such as cues and chemical manipulations. These signals might have a role in conflicts within and between species. The nature of the chemical interaction is important to take into account when studying why and how bacteria react to the chemical substances that are produced by other bacteria