Application of Granger causality to gene regulatory network discovery

Article no. 6314142Granger causality (GC) has been applied to gene regulatory network discovery using DNA microarray time-series data. Since the number of genes is much larger than the data length, a full model cannot be applied in a straightforward manner, hence GC is often applied to genes pairwisely. In this paper, firstly we investigate with synthetic data and point out how spurious causalities (false discoveries) may emerge in pairwise GC detection. In addition, spurious causalities may also arise if the order of the vector autoregressive model is not high enough. Therefore, besides using a suitable model order, we recommend a full model over pairwise GC. This is possible if pairwise GC is first used to identify a network of interactions among only a few genes, and then all these interactions are validated with a full model again. If a full model is not possible, we recommend using model validation techniques to remove spurious discoveries. Secondly, we apply pairwise GC with model validation to a real dataset (HeLa). To estimate the model order, the Akaike information criterion is found to be more suitable than the Bayesian information criterion. Degree distribution and network hubs are obtained and compared with previous publications. The hubs tend to act as sources of interactions rather than receivers of interactions. © 2012 IEEE.published_or_final_versio

Meta-analysis on gene regulatory networks discovered by pairwise Granger causality

Identifying regulatory genes partaking in disease development is important to medical advances. Since gene expression data of multiple experiments exist, combining results from multiple gene regulatory network discoveries offers higher sensitivity and specificity. However, data for multiple experiments on the same problem may not possess the same set of genes, and hence many existing combining methods are not applicable. In this paper, we approach this problem using a number of meta-analysis methods and compare their performances. Simulation results show that vote counting is outperformed by methods belonging to the Fisher's chi-square (FCS) family, of which FCS test is the best. Applying FCS test to the real human HeLa cell-cycle dataset, degree distributions of the combined network is obtained and compared with previous works. Consulting the BioGRID database reveals the biological relevance of gene regulatory networks discovered using the proposed method.published_or_final_versio

Are there enormous age-trends in stable carbon isotope ratios of oak tree rings?

We test a recent prediction that stable carbon isotope ratios from UK oaks will display age-trends of more than 4‰ per century by measuring >5400 carbon isotope ratios from the late-wood alpha-cellulose of individual rings from 18 modern oak trees and 50 building timbers spanning the 9th to 21st centuries. After a very short (c.5 years) juvenile phase with slightly elevated values, the number of series that show rising and falling trends is almost equal (33:35) and the average trend is almost zero. These results are based upon measuring and averaging the trends in individual time-series; the ‘mean of the slopes’ approach. We demonstrate that the more conventional ‘slope of the mean’ approach can produce strong but spurious ‘age-trends’ even when the constituent series are flat, with zero slope and zero variance. We conclude that it is safe to compile stable carbon isotope chronologies from UK oaks without de-trending. The isotope chronologies produced in this way are not subject to the ‘segment length curse’, which applies to growth measurements, such as ring width or density, and have the potential to retain very long-term climate signals

Absence of Age‐Related Trends in Stable Oxygen Isotope Ratios From Oak Tree Rings

The potential for age‐related trends in the stable oxygen isotope ratios of latewood alpha cellulose was investigated in samples of living oak trees and historic building timbers from the UK. When the series are examined individually, it is clear that the strongest trends in individual trees and timbers reflect concurrent trends in climate. Nonclimatic trends are very small and represent random noise that can be removed by averaging. If the same data are analyzed using the more conventional approach of aligning the series by ring number and fitting a regression line, so that the magnitude of the age trend is based on the slope of the mean and the statistical significance on the correlation coefficient, the results are very different. We demonstrate that this conventional approach regularly produces spurious age trends with grossly inflated probabilities, because of offsets in the mean values of series of different length. We conclude that there is no need to detrend stable oxygen isotope series from individual trees or timbers of oak from the UK and that to do so would remove important climatic information. Long isotope chronologies can safely be constructed by combining data from multiple individual trees, or by pooling material from trees prior to chemical treatment and isotopic measurement. Age‐related trends may occur in other species or in other regions, but where they have been identified using the conventional “slope of the mean” approach they should be reassessed using the “mean of the slope” approach.</p

Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

Short-lived juvenile effects observed in stable carbon and oxygen isotopes of UK oak trees and historic building timbers

Stable carbon (δ13C) and oxygen (δ18O) isotope ratios were measured on the latewood α-cellulose of individual oak (Quercus robur L, Q. petraea Liebl.) samples from living trees and historic building timbers. This represents the type of material available to produce long tree-ring chronologies for north-western Europe including the UK and Ireland. Results from the juvenile rings, those located closest to the pith, were compared with results from equivalent sections (representing the same calendar years) from independent master isotope chronologies that do not contain any juvenile wood, allowing any juvenile offsets and trends to be separated from those caused by environmental change. Oak timbers from archaeological sources are often relatively short (<100 years). Therefore, removing the first 50 rings, as is typical for Pinus sp., would severely constrain the material available for chronology construction. The aim of this study was to determine the magnitude and duration of juvenile effects, including the detection of trends, offsets and their influence upon signal strength. The results show clearly that juvenile effects for oak from central England are very small and short-lived and that removing merely the first five rings closest to the pith is sufficient to avoid them. This result greatly increases the potential for building long and well-replicated stable isotope chronologies using archived oak samples from historic building timbers, allowing high-resolution climate reconstructions to be produced for the highly-populated regions, where oak is abundant and which are currently under-represented in regional palaeoclimate reconstructions

The ‘Hothaps’ programme for assessing climate change impacts on occupational health and productivity: an invitation to carry out field studies

The ‘high occupational temperature health and productivity suppression’ programme (Hothaps) is a multi-centre health research and prevention programme aimed at quantifying the extent to which working people are affected by, or adapt to, heat exposure while working, and how global heating during climate change may increase such effects. The programme will produce essential new evidence for local, national and global assessment of negative impacts of climate change that have largely been overlooked. It will also identify and evaluate preventive interventions in different social and economic settings

Natural History, Microbes and Sequences: Shouldn't We Look Back Again to Organisms?

The discussion on the existence of prokaryotic species is reviewed. The demonstration that several different mechanisms of genetic exchange and recombination exist has led some to a radical rejection of the possibility of bacterial species and, in general, the applicability of traditional classification categories to the prokaryotic domains. However, in spite of intense gene traffic, prokaryotic groups are not continuously variable but form discrete clusters of phenotypically coherent, well-defined, diagnosable groups of individual organisms. Molecularization of life sciences has led to biased approaches to the issue of the origins of biodiversity, which has resulted in the increasingly extended tendency to emphasize genes and sequences and not give proper attention to organismal biology. As argued here, molecular and organismal approaches that should be seen as complementary and not opposed views of biology

A new two-phase dimeticone pediculicide shows high efficacy in a comparative bioassay

Background: \ud Dimeticones kill head lice by physical means. Here we assessed in a comparative bioassay the ex vivo efficacy of "NYDA® sensitiv", a new two-phase dimeticone-based pediculicide similar to a product established on the market, but without fragrances.\ud \ud Methods:\ud We compared efficacy of the new product to a positive dimeticone control group, a sample of four other insecticidal and natural head lice products marketed in Germany, and an untreated control. In a bioassay, lice were exposed ex vivo to products and examined for activity for up to 24 hours, following a standard protocol.\ud \ud Results:\ud After 6 and 24 hours, 13.7 and 88.5% of untreated control lice did not show major vital signs. In contrast, no lice showed major vital signs 5 minutes after treatment with the new product or the control dimeticone group (NYDA®). This effect persisted at all observation points (100% efficacy). Efficacy of 0.5% permethrin (Infectopedicul®) ranged between 76 and 96% in evaluations between 5 min and 6 hours. All lice treated with a coconut-based compound (mosquito® Läuseshampoo) did not show major vital signs after 5 min, but mortality was only 58% after one hour. Pyrethrum extract (Goldgeist® forte) showed an efficacy of 22 - 52% between 5 min and 3 hours after treatment; after 6 hours, 76% of lice were judged dead. An oxyphthirine®-based compound (Liberalice DUO LP-PRO®) killed 22 - 54% of lice in the first 6 hours.\ud \ud Conclusions:\ud The two-phase dimeticone compound NYDA® sensitiv is highly efficacious. The removal of fragrances as compared to an established dimeticone product did not affect in vitro efficacy