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Dennehy, J.

Publications and source records attributed to Dennehy, J..

3 recordsLinked to original sources

Laboratory efficacy of a solar-powered spatial repellent device against Anopheles mosquitoes

Spatial repellents represent a promising approach to complement existing malaria vector control interventions by reducing contact between mosquitoes and humans. However, the efficacy of passive spatial repellent devices may be affected by environmental conditions, particularly temperature and airflow, which can influence the release of volatile active ingredients. Active-release devices may provide more consistent delivery of spatial repellent compounds. We investigated the efficacy of a commercially available battery-powered spatial repellent device and a low-power solar-powered device designed for potential use in Africa. Laboratory trials were conducted to evaluate the efficacy of the two spatial repellent devices against Anopheles mosquitoes. Protective efficacy was assessed by comparing mosquito probing on human participants during spatial-repellent and control tests. The effect of the devices on mosquito entry into the test chamber was also assessed. The protective efficacy was 86% with the commercial battery-powered device and 80% with the low-power solar-powered device. A Wilcoxon rank-sum test showed that there was no significant difference between the performance of the two devices in terms of protective efficacy (p = 0.856) or entry inhibition (p = 0.7989). The low-power device could be charged using a small, household-level photovoltaic panel, to provide a potentially practical means of delivering spatial repellents in off-grid settings.

ecology↗

WxS-QC - a quality control pipeline for human Whole-Genome and Whole Exome sequencing cohorts

MotivationWhole-exome (WES) and whole-genome (WGS) sequencing are rapidly becoming preferred methods for population-scale analysis of the human genetic landscape. However, there are currently no standardized quality control (QC) pipelines for human WES and WGS datasets. Moveover, there are no open datasets that can be used to test QC pipelines, because most projects (like 1000 genomes and gnomAD) publish only post-QC results. ResultsWe present WxS-QC, a powerful, scalable, and convenient pipeline for the QC of human WGS and WES cohorts, developed at the Wellcome Sanger Institute (WSI). Our pipeline is based on a deep refactoring of the gnomAD quality control pipeline code and is aligned with current best practices in WGS/WES cohort data QC. It offers a set of novel QC techniques, automatic export of resulting graphs and summary tables, excellent performance and scalability, and incorporates comprehensive documentation. To test our pipeline and similar solutions, we also assembled an open dataset with all required metadata. Availability and implementationThe pipeline code is written in Python using the Hail library and is freely available under the BSD-3 license here: https://github.com/wtsi-hgi/wxs-qc. It can run in any UNIX-like environment and has been able to efficiently process cohorts of up to 200,000 whole-exome samples with the potential to handle bigger datasets, depending on the available hardware. The detailed description of the pipeline, resources and test data is available in the pipeline documentation: https://github.com/wtsi-hgi/wxs-qc/blob/main/README.md The open test dataset is available to download from https://wxs-qc-data.cog.sanger.ac.uk/wxs-qc_public_dataset_v3.tar. An example of test dataset analysis is available in the supplementary materials.

bioinformatics↗

The role of incoherent feedforward circuits in regulating precision of event timing

Triggering of cellular events often relies on the level of a key gene product crossing a critical threshold. Achieving precision in event timing in spite of noisy gene expression facilitates high-fidelity functioning of diverse processes from biomolecular clocks, apoptosis and cellular differentiation. Here we investigate the role of an incoherent feedforward circuit in regulating the time taken by a bacterial virus (bacteriophage lambda) to lyse an infected Escherichia coli cell. Lysis timing is the result of expression and accumulation of a single lambda protein (holin) in the E. coli cell membrane up to a critical threshold level, which triggers the formation of membrane lesions. This easily visualized process provides a simple model system for characterizing event-timing stochasticity in single cells. Intriguingly, lambdas lytic pathway synthesizes two functionally opposite proteins: holin and antiholin from the same mRNA in a 2:1 ratio. Antiholin sequesters holin and inhibits the formation of lethal membrane lesions, thus creating an incoherent feedforward circuit. We develop and analyze a stochastic model for this feedforward circuit that considers correlated bursty expression of holin/antiholin, and their concentrations are diluted from cellular growth. Interestingly, our analysis shows the noise in timing is minimized when both proteins are expressed at an optimal ratio, hence revealing an important regulatory role for antiholin. These results are in agreement with single cell data, where removal of antiholin results in enhanced stochasticity in lysis timing.

systems biology↗