Literature-based priors for gene regulatory networks

Motivation: The use of prior knowledge to improve gene regulatory network modelling has often been proposed. In this paper we present the first research on the massive incorporation of prior knowledge from literature for Bayesian network learning of gene networks. As the publication rate of scientific papers grows, updating online databases, which have been proposed as potential prior knowledge in past rese-arch, becomes increasingly challenging. The novelty of our approach lies in the use of gene-pair association scores that describe the over-lap in the contexts in which the genes are mentioned, generated from a large database of scientific literature, harnessing the information contained in a huge number of documents into a simple, clear format. Results: We present a method to transform such literature-based gene association scores to network prior probabilities, and apply it to learn gene sub-networks for yeast, E. coli and Human organisms. We also investigate the effect of weighting the influence of the prior know-ledge. Our findings show that literature-based priors can improve both the number of true regulatory interactions present in the network and the accuracy of expression value prediction on genes, in comparison to a network learnt solely from expression data. Networks learnt with priors also show an improved biological interpretation, with identified subnetworks that coincide with known biological pathways. Contact

Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data

Background: The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. Results: We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gammasarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. Conclusion: The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523

Human rights & intellectual property for universal access to new essential medicines

This chapter illustrates how human rights principles can help governments, even those with the most modest budgets, scale-up universal access to expensive essential medicines. The key message is that governments have legally binding human rights obligations to immediately take steps to provide essential medicines. These steps include making a maximum of public resources available to finance essential medicines, particularly for vulnerable and marginalized groups, and using those resources efficiently. Crucially, using mechanisms to control medicines prices and, in the case of high priced patented medicines, the use of TRIPS flexibilities, is aligned with governments’ duties under human rights law to ensure access to essential medicines. Moreover, the right to health imposes duties on the international community of States and the pharmaceutical industry to respect and protect access to essential medicines

Deuterium retention in tungsten and tungsten: tantalum alloys exposed to high-flux deuterium plasmas

A direct comparison of deuterium retention in samples of tungsten and two grades of tungsten-tantalum alloys-W-1% Ta and W-5% Ta, exposed to deuterium plasmas (ion flux similar to 10(24) m(-2) s(-1), ion energy at the biased target similar to 50 eV) at the plasma generator Pilot-PSI was performed using thermal desorption spectroscopy (TDS). No systematic difference in terms of total retention in tungsten and tungsten-tantalum was identified. The measured retention value for each grade did not deviate by more than 24% from the value averaged over the three grades exposed to the same conditions. No additional desorption peaks appeared in the TDS spectra of the W-Ta samples as compared with the W target, indicating that no additional kinds of traps are introduced by the alloying of W with Ta. In the course of the experiment the same samples were exposed to the same plasma conditions several times, and it is demonstrated that samples with the history of prior exposures yield an increase in deuterium retention of up to 130% under the investigated conditions compared with the samples that were not exposed before. We consider this as evidence that exposure of the considered materials to ions with energy below the displacement threshold generates additional traps for deuterium. The positions of the release peaks caused by these traps are similar for W and W-Ta, which indicates that the corresponding traps are of the same kind