epiPATH: an information system for the storage and management of molecular epidemiology data from infectious pathogens.

Abstract Background Most research scientists working in the fields of molecular epidemiology, population and evolutionary genetics are confronted with the management of large volumes of data. Moreover, the data used in studies of infectious diseases are complex and usually derive from different institutions such as hospitals or laboratories. Since no public database scheme incorporating clinical and epidemiological information about patients and molecular information about pathogens is currently available, we have developed an information system, composed by a main database and a web-based interface, which integrates both types of data and satisfies requirements of good organization, simple…

Disrupted PGR-B and ESR1 signaling underlies preconceptional defective decidualization linked to severe preeclampsia

AbstractDecidualization of the uterine mucosa drives the maternal adaptation to invasion by the placenta. Appropriate depth of placental invasion is needed to support a healthy pregnancy; shallow invasion is associated with the development of severe preeclampsia (sPE). Maternal contribution to sPE through failed decidualization is an important determinant of placental phenotype. However, the molecular mechanism underlaying the in vivo defect linking decidualization to sPE is unknown. Here, we discover the footprint encoding this decidualization defect comprising of 166 genes using global gene expression profiling in decidua from women who developed sPE in a previous pregnancy. This signatur…

A Novel Approach to Identify Candidate Prognostic Factors for Hepatitis C Treatment Response Integrating Clinical and Viral Genetic Data

The combined therapy of pegylated interferon (IFN) plus ribavirin (RBV) has been for a long time the standard treatment for patients infected with hepatitis C virus (HCV). In the case of genotype 1, only 38%–48% of patients have a positive response to the combined treatment. In previous studies, viral genetic information has been occasionally included as a predictor. Here, we consider viral genetic variation in addition to 11 clinical and 19 viral populations and evolutionary parameters to identify candidate baseline prognostic factors that could be involved in the treatment outcome. We obtained potential prognostic models for HCV subtypes la and lb in combination as well as separately. We …

Understanding disease mechanisms with models of signaling pathway activities

Background Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is one of the main challenges in the analysis of genomic data and is on the basis of the future implementation of precision medicine. Results Here we propose a simple probabilistic model in which signaling pathways are separated into elementary sub-pathways or signal transmission circuits (which ultimately trigger cell functions) and then transforms gene expression measurements into probabilities of activation of such signal transmission circuits. Using this model, differential activation of such circuits between biological conditions can be estimated. Thus, circuit activation s…

Identification and Characterization of Extracellular Vesicles and Its DNA Cargo Secreted During Murine Embryo Development

Extracellular vesicles (EVs) are known to transport DNA, but their implications in embryonic implantation are unknown. The aim of this study was to investigate EVs production and secretion by preimplantation embryos and assess their DNA cargo. Murine oocytes and embryos were obtained from six- to eight-week-old females, cultured until E4.5 and analyzed using transmission electron microscopy to examine EVs production. EVs were isolated from E4.5-day conditioned media and quantified by nanoparticle tracking analysis, characterized by immunogold, and their DNA cargo sequenced. Multivesicular bodies were observed in murine oocytes and preimplantation embryos together with the secretion of EVs t…

Embryo ATP production can be modulated by maternal mitochondrial DNA secreted from the human endometrium in extracellular vesicles

Reference genome assessment from a population scale perspective: an accurate profile of variability and noise.

Abstract Motivation Current plant and animal genomic studies are often based on newly assembled genomes that have not been properly consolidated. In this scenario, misassembled regions can easily lead to false-positive findings. Despite quality control scores are included within genotyping protocols, they are usually employed to evaluate individual sample quality rather than reference sequence reliability. We propose a statistical model that combines quality control scores across samples in order to detect incongruent patterns at every genomic region. Our model is inherently robust since common artifact signals are expected to be shared between independent samples over misassembled regions …