Temporal Bayesian classifiers for modelling muscular dystrophy expression data

The analysis of microarray data from time-series experiments requires specialised algorithms, which take the temporal ordering of the data into account. In this paper we explore a new architecture of Bayesian classifier that can be used to understand how biological mechanisms differ with respect to time. We show that this classifier improves the classification of microarray data and at the same time ensures that the models can easily be analysed by biologists by incorporating time transparently. In this paper we focus on data that has been generated to explore different types of muscular dystrophy

Literature-based priors for gene regulatory networks

Motivation: The use of prior knowledge to improve gene regulatory network modelling has often been proposed. In this paper we present the first research on the massive incorporation of prior knowledge from literature for Bayesian network learning of gene networks. As the publication rate of scientific papers grows, updating online databases, which have been proposed as potential prior knowledge in past rese-arch, becomes increasingly challenging. The novelty of our approach lies in the use of gene-pair association scores that describe the over-lap in the contexts in which the genes are mentioned, generated from a large database of scientific literature, harnessing the information contained in a huge number of documents into a simple, clear format. Results: We present a method to transform such literature-based gene association scores to network prior probabilities, and apply it to learn gene sub-networks for yeast, E. coli and Human organisms. We also investigate the effect of weighting the influence of the prior know-ledge. Our findings show that literature-based priors can improve both the number of true regulatory interactions present in the network and the accuracy of expression value prediction on genes, in comparison to a network learnt solely from expression data. Networks learnt with priors also show an improved biological interpretation, with identified subnetworks that coincide with known biological pathways. Contact

Vaginal Microbicides: Detecting Toxicities in Vivo that Paradoxically Increase Pathogen Transmission

BACKGROUND: Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9) and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a) Directly tests for toxic effects that increase susceptibility to HSV-2, (b) Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c) Identifies those toxic effects that best correlate with the increased HSV susceptibility. METHODS: Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50) at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9), cationic (benzalkonium chloride, BZK), anionic (sodium dodecylsulfate, SDS), the pair of detergents in C31G (C14AO and C16B); one surface active agent (chlorhexidine); two non-detergents (BufferGel®, and sulfonated polystyrene, SPS); and HEC placebo gel (hydroxyethylcellulose). Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. RESULTS: A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible sign of the N9 toxic effect that increased susceptibility at 12 hours. Toxic effects that occurred contemporaneously with increased susceptibility were rapid exfoliation and re-growth of epithelial cell layers, entry of macrophages into the vaginal lumen, and release of one or more inflammatory cytokines (Il-1β, KC, MIP 1α, RANTES). The non-detergent microbicides and HEC placebo caused no significant increase in susceptibility or toxic effects. CONCLUSION: This mouse HSV-2 model provides a sensitive method to detect microbicide-induced toxicities that increase susceptibility to infection. In this model, there was no concentration at which detergents provided protection without significantly increasing susceptibility.JHU Woodrow Wilson Fellowship; National Institutes of Health (Program Project A1 45967

Joint modeling of ChIP-seq data via a Markov random field model

Chromatin ImmunoPrecipitation-sequencing (ChIP-seq) experiments have now become routine in biology for the detection of protein-binding sites. In this paper, we present a Markov random field model for the joint analysis of multiple ChIP-seq experiments. The proposed model naturally accounts for spatial dependencies in the data, by assuming first-order Markov dependence and, for the large proportion of zero counts, by using zero-inflated mixture distributions. In contrast to all other available implementations, the model allows for the joint modeling of multiple experiments, by incorporating key aspects of the experimental design. In particular, the model uses the information about replicates and about the different antibodies used in the experiments. An extensive simulation study shows a lower false non-discovery rate for the proposed method, compared with existing methods, at the same false discovery rate. Finally, we present an analysis on real data for the detection of histone modifications of two chromatin modifiers from eight ChIP-seq experiments, including technical replicates with different IP efficiencies

A continuously updated, geospatially rectified database of utility-scale wind turbines in the United States.

Over 60,000 utility-scale wind turbines are installed in the United States as of October, 2019, representing over 97 gigawatts of electric power capacity; US wind turbine installations continue to grow at a rapid pace. Yet, until April 2018, no publicly-available, regularly updated data source existed to describe those turbines and their locations. Under a cooperative research and development agreement, analysts from three organizations collaborated to develop and release the United States Wind Turbine Database (USWTDB) - a publicly available, continuously updated, spatially rectified data source of locations and attributes of utility-scale wind turbines in the United States. Technical specifications and wind facility data, incorporated from five sources, undergo rigorous quality control. The location of each turbine is visually verified using high-resolution aerial imagery. The quarterly-updated data are available in a variety of formats, including an interactive web application, comma-separated values (CSV), shapefile, and application programming interface (API). The data are used widely by academic researchers, engineers and developers from wind energy companies, government agencies, planners, educators, and the general public

Dysfunctional transcripts are formed by alternative polyadenylation in OPMD

Molecular Technology and Informatics for Personalised Medicine and HealthFunctional Genomics of Muscle, Nerve and Brain Disorder

Two Boundaries Separate Borrelia burgdorferi Populations in North America

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s of hosts required for sustaining tick populations. Multilocus sequence typing and complementary population analytical tools were used to evaluate B. burgdorferi samples collected in the Northeastern, Upper Midwestern, and Far-Western United States and Canada. The spatial distribution of sequence types (STs) and inferred population boundaries suggest that the current populations are geographically separated. One major population boundary separated western B. burgdorferi populations transmitted by Ixodes pacificus in California from Eastern populations transmitted by I. scapularis; the other divided Midwestern and Northeastern populations. However, populations from all three regions were genetically closely related. Together, our findings suggest that although the contemporary populations of North American B. burgdorferi now com- prise three geographically separated subpopulations with no or limited gene flow among them, they arose from a common ancestral population. A comparative analysis of the B. burgdorferi outer surface protein C (ospC) gene revealed novel linkages and provides additional insights into the genetic characteristics of strains