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

Tectono-stratigraphic evolution and crustal architecture of the Orphan Basin during North Atlantic rifting

The Orphan Basin is located in the deep offshore of the Newfoundland margin, and it is bounded by the continental shelf to the west, the Grand Banks to the south, and the continental blocks of Orphan Knoll and Flemish Cap to the east. The Orphan Basin formed in Mesozoic time during the opening of the North Atlantic Ocean between eastern Canada and western Iberia–Europe. This work, based on well data and regional seismic reflection profiles across the basin, indicates that the continental crust was affected by several extensional episodes between the Jurassic and the Early Cretaceous, separated by events of uplift and erosion. The preserved tectono-stratigraphic sequences in the basin reveal that deformation initiated in the eastern part of the Orphan Basin in the Jurassic and spread towards the west in the Early Cretaceous, resulting in numerous rift structures filled with a Jurassic–Lower Cretaceous syn-rift succession and overlain by thick Upper Cretaceous to Cenozoic post-rift sediments. The seismic data show an extremely thinned crust (4–16 km thick) underneath the eastern and western parts of the Orphan Basin, forming two sub-basins separated by a wide structural high with a relatively thick crust (17 km thick). Quantifying the crustal architecture in the basin highlights the large discrepancy between brittle extension localized in the upper crust and the overall crustal thinning. This suggests that continental deformation in the Orphan Basin involved, in addition to the documented Jurassic and Early Cretaceous rifting, an earlier brittle rift phase which is unidentifiable in seismic data and a depth-dependent thinning of the crust driven by localized lower crust ductile flow

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

Can the intake of antiparasitic secondary metabolites explain the low prevalence of hemoparasites among wild Psittaciformes?

Background: Parasites can exert selection pressure on their hosts through effects on survival, on reproductive success, on sexually selected ornament, with important ecological and evolutionary consequences, such as changes in population viability. Consequently, hemoparasites have become the focus of recent avian studies. Infection varies significantly among taxa. Various factors might explain the differences in infection among taxa, including habitat, climate, host density, the presence of vectors, life history and immune defence. Feeding behaviour can also be relevant both through increased exposure to vectors and consumption of secondary metabolites with preventative or therapeutic effects that can reduce parasite load. However, the latter has been little investigated. Psittaciformes (parrots and cockatoos) are a good model to investigate these topics, as they are known to use biological control against ectoparasites and to feed on toxic food. We investigated the presence of avian malaria parasites (Plasmodium), intracellular haemosporidians (Haemoproteus, Leucocytozoon), unicellular flagellate protozoans (Trypanosoma) and microfilariae in 19 Psittaciformes species from a range of habitats in the Indo-Malayan, Australasian and Neotropical regions. We gathered additional data on hemoparasites in wild Psittaciformes from the literature. We considered factors that may control the presence of hemoparasites in the Psittaciformes, compiling information on diet, habitat, and climate. Furthermore, we investigated the role of diet in providing antiparasitic secondary metabolites that could be used as self-medication to reduce parasite load. Results: We found hemoparasites in only two of 19 species sampled. Among them, all species that consume at least one food item known for its secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, were free from hemoparasites. In contrast, the infected parrots do not consume food items with antimalarial or even general antiparasitic properties. We found that the two infected species in this study consumed omnivorous diets. When we combined our data with data from studies previously investigating blood parasites in wild parrots, the positive relationship between omnivorous diets and hemoparasite infestation was confirmed. Individuals from open habitats were less infected than those from forests. Conclusions: The consumption of food items known for their secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, as well as the higher proportion of infected species among omnivorous parrots, could explain the low prevalence of hemoparasites reported in many vertebrates

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

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