Louise, J. | Search bioRxiv

bioRxiv2024

Functional lung imaging identifies peripheral ventilation changes in mice with muco-obstructive lung disease

{beta}-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease, with impaired mucociliary clearance, mucus obstruction, chronic airway inflammation, structural lung damage, and altered lung function. The aim of this study was to undertake a comprehensive lung function and mechanics analysis of the adult {beta}-ENaC-Tg model. {beta}-ENaC-Tg and wild-type littermates underwent X-ray Velocimetry (XV) scans using a Permetium XV scanner (4DMedical, Melbourne, Australia). For comparative lung mechanics, lung function assessments were conducted with a flexiVent system. XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in {beta}-ENaC-Tg mice. Spatial analysis of ventilation maps indicated increased ventilation variability in the peripheral lung regions, as well as an increased proportion of under-ventilated areas. The flexiVent analysis indicated that compared to wild-types, {beta}-ENaC-Tg mice have a significantly more compliant lungs with increased inspiratory capacity, reduced tissue elastance and increased hysteresivity (heterogeneity), suggesting loss of parenchymal integrity. This research highlights the utility of XV imaging in evaluating ventilation defects in the {beta}-ENaC-Tg model and provides a comprehensive lung function analysis.

physiology↗

bioRxiv2022

Data Processing Choices Can Affect Findings in Differential Methylation Analyses: An Investigation Using Data from the LIMIT RCT

ObjectiveA wide array of methods exist for processing and analysing DNA methylation data. We aimed to perform a systematic comparison of the behaviour of these methods, using cord blood DNAm from the LIMIT RCT, in relation to detecting hypothesised effects of interest (intervention and pre-pregnancy maternal BMI) as well as effects known to be spurious, and known to be present. MethodsDNAm data, from 645 cord blood samples analysed using Illumina 450K BeadChip arrays, were normalised using three different methods (with probe filtering undertaken pre- or post-normalisation). Batch effects were handled with a supervised algorithm, an unsupervised algorithm, or adjustment in the analysis model. Analysis was undertaken with and without adjustment for estimated cell type proportions. The effects estimated included intervention and BMI (effects of interest in the original study), infant sex and randomly assigned groups. Data processing and analysis methods were compared in relation to number and identity of differentially methylated probes, rankings of probes by p value and log-fold-change, and distributions of p values and log-fold-change estimates. ResultsThere were differences corresponding to each of the processing and analysis choices. Importantly, some combinations of data processing choices resulted in a substantial number of spurious significant findings. We recommend greater emphasis on replication and greater use of sensitivity analyses. Clinical Trials RegistrationACTRN12607000161426

bioinformatics↗