Constructing gene regulatory networks from microarray data using non-Gaussian pair-copula Bayesian networks.

Many biological and biomedical research areas such as drug design require analyzing the Gene Regulatory Networks (GRNs) to provide clear insight and understanding of the cellular processes in live cells. Under normality assumption for the genes, GRNs can be constructed by assessing the nonzero elements of the inverse covariance matrix. Nevertheless, such techniques are unable to deal with non-normality, multi-modality and heavy tailedness that are commonly seen in current massive genetic data. To relax this limitative constraint, one can apply copula function which is a multivariate cumulative distribution function with uniform marginal distribution. However, since the dependency structures of different pairs of genes in a multivariate problem are very different, the regular multivariate copula will not allow for the construction of an appropriate model. The solution to this problem is using Pair-Copula Constructions (PCCs) which are decompositions of a multivariate density into a cascade of bivariate copula, and therefore, assign different bivariate copula function for each local term. In fact, in this paper, we have constructed inverse covariance matrix based on the use of PCCs when the normality assumption can be moderately or severely violated for capturing a wide range of distributional features and complex dependency structure. To learn the non-Gaussian model for the considered GRN with non-Gaussian genomic data, we apply modified version of copula-based PC algorithm in which normality assumption of marginal densities is dropped. This paper also considers the Dynamic Time Warping (DTW) algorithm to determine the existence of a time delay relation between two genes. Breast cancer is one of the most common diseases in the world where GRN analysis of its subtypes is considerably important; Since by revealing the differences in the GRNs of these subtypes, new therapies and drugs can be found. The findings of our research are used to construct GRNs with high performance, for various subtypes of breast cancer rather than simply using previous models.

Effects of morphine on the biomass and development rate of Chrysomya albiceps (Diptera: Calliphoridae), a forensically important species.

The aim of this study was to determine the effects of morphine on the biomass and development rate of Chrysomya albiceps (Diptera: Calliphoridae). C. albiceps, a well-known forensically important species which is among the first wave of faunal succession on human cadavers, which makes it a valuable source of information for the estimation of postmortem interval (PMI). Antemortem exposure to substances such as drugs and toxins may have an effect on the biomass and/or on the development rate of insects that feed on carcass, which may directly affect PMI estimation. In this study, three rabbits were administered 12.5, 25 or 50 mg/ml of morphine sulfate via ear perfusion over a period of 3 hours, and a fourth rabbit, which did not receive morphine, was used as a control. The rabbits were sacrificed using chloroform 30 minutes after morphine administration. The tissues were analyzed for the presence of morphine using HPLC-UV. Morphine was detected in all tissues of rabbits that received morphine, except in the bile and spleen of the rabbit which received 12.5 mg/ml dose of morphine. The presence of morphine in rabbit tissues retarded larval development rate, but accelerated the puparial development rate. The rate of development of C. albiceps larvae that fed on rabbits which received 25 and 50 mg/ml dosages of morphine was 9 days each. However, the rate of larval development was similar in the 12.5 mg/ml morphine group and the control; 6 days. Results of this study show that an underestimation of the postmortem interval of 72 h based on larval development and an overestimation of 24 to 48 h based on puparial development is possible if the presence of morphine in tissues is not considered. Moreover, the decreased larval development rate caused an increase larval length and weight compared with the control group. In this study, we found a strong correlation between the concentration of morphine administered and concentrations in rabbit tissues. In the estimation of PMI, it is recommended that effects of drugs such as morphine on the development of carcass colonizers be considered.