Analysing multiple types of molecular profiles simultaneously: Connecting the needles in the haystack

Background: It has been shown that a random-effects framework can be used to test the association between a gene's expression level and the number of DNA copies of a set of genes. This gene-set modelling framework was later applied to find associations between mRNA expression and microRNA expression, by defining the gene sets using target prediction information. Methods and results: Here, we extend the model introduced by Menezes et al. 2009 to consider the effect of not just copy number, but also of other molecular profiles such as methylation changes and loss-of-heterozigosity (LOH), on gene expression levels. We will consider again sets of measurements, to improve robustness of results and increase the power to find associations. Our approach can be used genome-wide to find associations and yields a test to help separate true associations from noise. We apply our method to colon and to breast cancer samples, for which genome-wide copy number, methylation and gene expression profiles are available. Our findings include interesting gene expression-regulating mechanisms, which may involve only one of copy number or methylation, or both for the same samples. We even are able to find effects due to different molecular mechanisms in different samples. Conclusions: Our method can equally well be applied to cases where other types of molecular (high-dimensional) data are collected, such as LOH, SNP genotype and microRNA expression data. Computationally efficient, it represents a flexible and powerful tool to study associations between high-dimensional datasets. The method is freely available via the SIM BioConductor package

A regional survey of emerging hot climate conditions in Portugal and the new challenge to animal housing

Portugal, located in the South-western Europe, is characterised by a Mediterranean climate with hot and dry summer. According to data from Portuguese IM (Instituto de Meteorologia) during the last decade, summer temperatures tend to be higher, and several heat waves have occurred, with temperatures above 40 oC. During summer, days with high temperatures and heat waves are becoming more and more common in Portugal. The past four summers have been among the hottest ever registered. These frequently high temperatures can cause problems in intensive animal production. In most cases, the livestock buildings are not prepared for animal production under high temperatures and most of them do not have environmental control equipments adequate to control indoor environment under such conditions. From a geographical point of view, and examining climatic data, we find two regions (Alentejo and Trás-os-Montes) where high temperatures are more usual and summer tend to be hot. In these two regions, livestock is quite relevant and have a great significance to the regional economy. Two locations were chosen in these regions to register and analyse air temperature in order to identify the occurrence of hot climate conditions; and to evaluate its influence on the inside animal housing climate

A Combining Forecasting Modeling and Its Application

Part 5: Modelling and SimulationInternational audienceThe supply chain coordination has abstracted more and more attention from industries and academics. This paper studies a Bayesian combination forecasting model to integrate multiple forecasting resources and coordinate forecasting process among partners in retail supply chain. The simulation results based on the retail sales data show the effectiveness of this Bayesian combination forecasting model to coordinate the collaborative forecasting process. This Bayesian combination forecasting model can improve demand forecasting accuracy of supply chain

A test for comparing two groups of samples when analyzing multiple omics profiles

Background: A number of statistical models has been proposed for studying the association between gene expression and copy number data in integrated analysis. The next step is to compare association patterns between different groups of samples.Results: We propose a method, named dSIM, to find differences in association between copy number and gene expression, when comparing two groups of samples. Firstly, we use ridge regression to correct for the baseline associations between copy number and gene expression. Secondly, the global test is applied to the corrected data in order to find differences in association patterns between two groups of samples. We show that dSIM detects differences even in small genomic regions in a simulation study. We also apply dSIM to two publicly available breast cancer datasets and identify chromosome arms where copy number led gene expression regulation differs between positive and negative estrogen receptor samples. In spite of differing genomic coverage, some selected arms are identified in both datasets.Conclusion: We developed a flexible and robust method for studying association differences between two groups of samples while integrating genomic data from different platforms. dSIM can be used with most types of microarray/sequencing data, including methylation and microRNA expression. The method is implemented in R and will be made part of the BioConductor package SIM

Market proliferation and the impact of locational complexity on network restructuring

This manuscript investigates the problem of locational complexity, a type of complexity that emanates from a company's territorial strategy. Using an entropy-based measure for supply chain structural complexity (pars-complexity), we develop a theoretical framework for analysing the effects of locational complexity on the profitability of service/manufacturing networks. The proposed model is used to shed light on the reasons why network restructuring strategies may result ineffective at reducing complexity-related costs. Our contribution is three-fold. First, we develop a novel mathematical formulation of a facility location problem that integrates the pars-complexity measure in the decision process. Second, using this model, we propose a decomposition of the penalties imposed by locational complexity into (a) an intrinsic cost of structural complexity; and (b) an avoidable cost of ignoring such complexity in the decision process. Such a decomposition is a valuable tool for identifying more effective measures for tackling locational complexity, moreover, it has allowed us to provide an explanation to the so-called addiction to growth within the locational context. Finally, we propose three alternative strategies that attempt to mimic different approaches used in practice by companies that have engaged in network restructuring processes. The impact of those approaches is evaluated through extensive numerical experiments. Our experimental results suggest that network restructuring efforts that are not accompanied by a substantial reduction on the target market of the company, fail at reducing complexity-related costs and, therefore, have a limited impact on the company's profitability

Genomic profiling by DNA amplification of laser capture microdissected tissues and array CGH.

Comparative genomic hybridization by means of BAC microarrays (array CGH) allows high-resolution profiling of copy-number aberrations in tumor DNA. However, specific genetic lesions associated with small but clinically relevant tumor areas may pass undetected due to intra-tumor heterogeneity and/or the presence of contaminating normal cells. Here, we show that the combination of laser capture microdissection, phi29 DNA polymerase-mediated isothermal genomic DNA amplification, and array CGH allows genomic profiling of very limited numbers of cells. Moreover, by means of simple statistical models, we were able to bypass the exclusion of amplification distortions and variability prone areas, and to detect tumor-specific chromosomal gains and losses. We applied this new combined experimental and analytical approach to the genomic profiling of colorectal adenomatous polyps and demonstrated our ability to accurately detect single copy gains and losses affecting either whole chromosomes or small genomic regions from as little as 2 ng of DNA or 1000 microdissected cells

XY model in small-world networks

The phase transition in the XY model on one-dimensional small-world networks is investigated by means of Monte-Carlo simulations. It is found that long-range order is present at finite temperatures, even for very small values of the rewiring probability, suggesting a finite-temperature transition for any nonzero rewiring probability. Nature of the phase transition is discussed in comparison with the globally-coupled XY model.Comment: 5 pages, accepted in PR

Shortest paths on systems with power-law distributed long-range connections

We discuss shortest-path lengths $\ell(r)$ on periodic rings of size L supplemented with an average of pL randomly located long-range links whose lengths are distributed according to P_l \sim l^{-\xpn}. Using rescaling arguments and numerical simulation on systems of up to $10^7$ sites, we show that a characteristic length $\xi$ exists such that $\ell(r) \sim r$ for $r>\xi$. For small p we find that the shortest-path length satisfies the scaling relation \ell(r,\xpn,p)/\xi = f(\xpn,r/\xi). Three regions with different asymptotic behaviors are found, respectively: a) \xpn>2 where $\theta_s=1$, b) 1<\xpn<2 where 0<\theta_s(\xpn)<1/2 and, c) \xpn<1 where $\ell(r)$ behaves logarithmically, i.e. $\theta_s=0$. The characteristic length $\xi$ is of the form $\xi \sim p^{-\nu}$ with \nu=1/(2-\xpn) in region b), but depends on L as well in region c). A directed model of shortest-paths is solved and compared with numerical results.Comment: 10 pages, 10 figures, revtex4. Submitted to PR

Biochemical parameters of silver catfish (Rhamdia quelen) after transport with eugenol or essential oil of Lippia alba added to the water

The transport of live fish is a routine practice in aquaculture and constitutes a considerable source of stress to the animals. The addition of anesthetic to the water used for fish transport can prevent or mitigate the deleterious effects of transport stress. This study investigated the effects of the addition of eugenol (EUG) (1.5 or 3.0 mu L L-1) and essential oil of Lippia alba (EOL) (10 or 20 mu L L-1) on metabolic parameters (glycogen, lactate and total protein levels) in liver and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported for four hours in plastic bags (loading density of 169.2 g L-1). The addition of various concentrations of EUG (1.5 or 3.0 mu L L-1) and EOL (10 or 20 mu L L-1) to the transport water is advisable for the transportation of silver catfish, since both concentrations of these substances increased the levels of NPSH antioxidant and decreased the TBARS levels in the liver. In addition, the lower liver levels of glycogen and lactate in these groups and lower AChE activity in the brain (EOL 10 or 20 mu L L-1) compared to the control group indicate that the energetic metabolism and neurotransmission were lower after administration of anesthetics, contributing to the maintenance of homeostasis and sedation status.Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS/PRONEX) [10/0016-8]; Conselho Nacional de Pesquisa e Desenvolvimento Cientifico (CNPq) [470964/2009-0]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); CNPqinfo:eu-repo/semantics/publishedVersio