Statistical Tests for Detecting Differential RNA-Transcript Expression from Read Counts

As a fruit of the current revolution in sequencing technology, transcriptomes can now be analyzed at an unprecedented level of detail. These advances have been exploited for detecting differential expressed genes across biological samples and for quantifying the abundances of various RNA transcripts within one gene. However, explicit strategies for detecting the hidden differential abundances of RNA transcripts in biological samples have not been defined. In this work, we present two novel statistical tests to address this issue: a 'gene structure sensitive' Poisson test for detecting differential expression when the transcript structure of the gene is known, and a kernel-based test called Maximum Mean Discrepancy when it is unknown. We analyzed the proposed approaches on simulated read data for two artificial samples as well as on factual reads generated by the Illumina Genome Analyzer for two _C. elegans_ samples. Our analysis shows that the Poisson test identifies genes with differential transcript expression considerably better that previously proposed RNA transcript quantification approaches for this task. The MMD test is able to detect a large fraction (75%) of such differential cases without the knowledge of the annotated transcripts. It is therefore well-suited to analyze RNA-Seq experiments when the genome annotations are incomplete or not available, where other approaches have to fail

Development and evaluation of a diagnostic cytokine-release assay for Mycobacterium suricattae infection in meerkats (Suricata suricatta)

CITATION: Clarke, C., et al. 2017. Development and evaluation of a diagnostic cytokine-release assay for mycobacterium suricattae infection in meerkats (Suricata suricatta). BMC Veterinary Research, 13:2, doi:10.1186/s12917-016-0927-x.The original publication is available at http://bmcvetres.biomedcentral.comBackground: Sensitive diagnostic tools are necessary for the detection of Mycobacterium suricattae infection in meerkats (Suricata suricatta) in order to more clearly understand the epidemiology of tuberculosis and the ecological consequences of the disease in this species. We therefore aimed to develop a cytokine release assay to measure antigen-specific cell-mediated immune responses of meerkats. Results: Enzyme-linked immunosorbent assays (ELISAs) were evaluated for the detection of interferon-gamma (IFN-γ) and IFN-γ inducible protein 10 (IP-10) in meerkat plasma. An IP-10 ELISA was selected to measure the release of this cytokine in whole blood in response to Bovigam® PC-HP Stimulating Antigen, a commercial peptide pool of M. bovis antigens. Using this protocol, captive meerkats with no known M. suricattae exposure (n = 10) were tested and results were used to define a diagnostic cut off value (mean plus 2 standard deviations). This IP-10 release assay (IPRA) was then evaluated in free-living meerkats with known M. suricattae exposure, categorized as having either a low, moderate or high risk of infection with this pathogen. In each category, respectively, 24.7%, 27.3% and 82.4% of animals tested IPRA-positive. The odds of an animal testing positive was 14.0 times greater for animals with a high risk of M. suricattae infection compared to animals with a low risk. Conclusion: These results support the use of this assay as a measure of M. suricattae exposure in meerkat populations. Ongoing longitudinal studies aim to evaluate the value of the IPRA as a diagnostic test of M. suricattae infection in individual animals.http://bmcvetres.biomedcentral.com/articles/10.1186/s12917-016-0927-xPublisher's versio

Report on evaluation of trainee learning achievement : China FETPV Module 5 (weeks 2-3)

A threeweek intensive revision module was delivered in May and June 2012 as the final part of the two year China FETPV training programme involving a group of 14 trainees which had been selected by FAO. The second and third week were delivered by Cirad and FAO, the first by other trainers able to teach in Chinese. This was a revision module which covered a wide range of topics including biostatistics, disease frequency and causation, designing and evaluating animal health surveillance systems, outbreak investigations, risk assessment and risk communication, scientific writing, scientific presentations, and paper critiquing. The teaching was based on a combination of interactive lectures (with TurningPoint voting to enable audience participation), problem based group learning sessions with case study examples, and one to one mentoring on individual assignments. The teaching in weeks 2 and 3 was delivered jointly by four experienced veterinary epidemiologists from the Royal Veterinary College (Prof. Dirk Pfeiffer, Prof. Javier Guitian, Dr Julian Drewe) and Cirad, the French Research Centre for Agricultural Development (Sophie Molia). Overall learning achievement of trainees was moderate to good. The majority of trainees felt they improved by a lot or a moderate amount in 10 key skills identified at the end of the course, and indicated they would be happy to teach their colleagues some of their newly developed epidemiological skills. The trainees found certain areas difficult, in particular surveillance evaluation and quantitative risk assessment. A constraint to learning was the limited English language ability of several of the trainees. (Résumé d'auteur

Evaluation of the usefulness at national level of the dairy cattle health and production recording systems in Great Britain

The aim of this study was to formally evaluate, qualitatively, the ability of existing recording systems to generate accurate and reliable estimates of the frequency of selected health conditions in the dairy herd of Great Britain. Fifty-nine recording systems were identified, of which 36 had their key characteristics defined through a web-based questionnaire. Nineteen of them were further assessed following the SERVAL, a SuRveillance EVALuation framework against a set of 12 attributes: benefit, bias, communication, coverage, data collection, data management, data analysis, data completeness, flexibility, multiple utility, representativeness and stability/sustainability. The evaluated systems showed considerable differences in their coverage, implementation and objectives. There were overlaps in recorded conditions, with Johne's disease, bovine viral diarrhoea, mastitis and lameness being recorded by most of the systems. Selection bias, data ownership and lack of integration of data from different systems appeared to be a key limitation on the future use of existing systems for nationwide monitoring. The results showed that even though the individual systems can provide reliable estimates of dairy health for individual farmers, none of the systems alone could provide accurate and reliable estimates for any of the conditions of interest at national level

Thalidomide does not interact with P-glycoprotein

Background: There is growing clinical interest in thalidomide for the treatment of various disorders due to its anti-inflammatory, immunomodulatory, and anti-angiogenic properties. In numerous clinical trials thalidomide is used as an adjunct to standard therapy. Therefore, clinicians should be aware of all possible drug-drug interactions that might occur with this drug. P-glycoprotein (P-gp), a drug efflux transporter that is expressed in many tissues, is the cause of several drug-drug interactions. P-gp induction or inhibition can lead to ineffective therapy or side-effects. In this study, we investigated thalidomide's potential to cause drug-drug interactions on the level of P-gp. Methods: LS180 cells were incubated with thalidomide for 72h in order to determine P-gp induction using real-time RT-PCR. A human leukaemia cell line over-expressing MDR1 (CCRF-CEM/MDR1) was used to measure uptake of rhodamine 123, a P-gp substrate, in the presence of thalidomide. Dose-dependent and bi-directional transport of thalidomide through Caco-2 cell monolayers was performed to assess site-directed permeability. Transport rates were determined using HPLC including chiral separation of the thalidomide enantiomers. Results: Thalidomide did not induce P-gp expression in LS180 cells. The uptake of rhodamine 123 in CCRF cells over-expressing MDR1 was not influenced by co-incubation with thalidomide. The transport through Caco-2 monolayers was linear and the permeability was similar for both directions. No differences between the thalidomide enantiomers were observed. Conclusions: Our study indicates that thalidomide is neither a substrate, nor an inhibitor or an inducer of P-gp. Therefore, P-gp-related drug-drug interactions with thalidomide are not likel

Interaktionen kardialer und antiretroviraler Medikation

Zusammenfassung: Neue therapeutische Optionen der hochaktiven antiretroviralen Therapie (HAART) haben die Morbidität und Mortalität von HIV-infizierten Patienten deutlich gesenkt, so dass nun vermehrt die altersspezifischen Erkrankungen manifest werden, wie z. B. kardiovaskuläre Erkrankungen. Zusätzlich verursacht die HIV-Erkrankung selber eine gewisse kardiovaskuläre Morbidität. Aus diesem Grund gewinnt die Behandlung der kardiovaskulären Symptome eine zunehmende Bedeutung. Die Pharmakotherapie dieser HIV-positiven Patienten ist sehr komplex, da sie durch eine Polypharmazie aus Medikamenten mit einem hohen Interaktionspotential geprägt is