An automated respiratory data pipeline for waveform characteristic analysis

Abstract

Comprehensive and accurate analysis of respiratory and metabolic data is crucial to modelling congenital, pathogenic, and degenerative diseases converging on autonomic control failure. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. We present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs, and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface for uploading data files, setting waveform feature thresholds, and defining experimental variables. Breathe Easy was validated against manual selection by experts, which represents the current standard in the field. We demonstrate Breathe Easy's utility by examining a 2-year longitudinal study of an Alzheimer's Disease mouse model to assess contributions of forebrain pathology in disordered breathing. Breathe Easy provides an open-source respiratory analysis tool for all respiratory datasets.

Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes

“…Fourth, our experimental design was overpowered (i.e., n=16-21 vs 5-13 needed for power based on power analysis and n=7-8 reported in other manuscripts). Each respiratory/metabolic parameter for each physiological condition including room air, hypercapnia, and hypoxia was derived by quantifying the entire respiratory trace and analyzed between mutant and sibling controls by using a powerful linear mixed-effects regression model with animal type (experimental vs. control) as fixed effects, animal ID as a random effect and including sex as a variable (there was no sex specific effect) (Lusk et al, 2022).. Despite our experimental design and the extensive nature of our measurements, there remain several considerations in the interpretation of our data.…”

“…Respiratory waveforms were analyzed by the BASSPRO module of the Breathe Easy software to determine respiratory frequency (Vf), tidal volume (VT), minute ventilation (VE), oxygen consumption (VO2) and ventilatory equivalents for oxygen (VE/VO2) (Lusk et al, 2022). A power analysis was performed using the reported effect size in Abbott et al (2014) which used the same mouse model as we used here and 5-13 mice were necessary to observe a statistically significant result (Abbott et al (2014) was able to see a significant difference between two groups with n=7 mice).…”

“…In our experiments, the sample size for each group (TgDBH-Cre/+; Vglut2 flox/flox and control) exceeded 13. Results (Vf, VE, VT, VO2, VE/VO2) for room air and hypercapnic or hypoxic data were compared between TgDBH-Cre/+; Vglut2 flox/flox cohorts and sibling controls using a linear mixed-effects regression model with animal type (experimental vs. control) as fixed effects and animal ID as a random effect (Lusk et al, 2022)…”

Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes

“…Fourth, our experimental design was overpowered (i.e., n=16-21 vs 5-13 needed for power based on power analysis and n=7-8 reported in other manuscripts). Each respiratory/metabolic parameter for each physiological condition including room air, hypercapnia, and hypoxia was derived by quantifying the entire respiratory trace and analyzed between mutant and sibling controls by using a powerful linear mixed-effects regression model with animal type (experimental vs. control) as fixed effects, animal ID as a random effect and including sex as a variable (there was no sex specific effect) (Lusk et al, 2022 ).…”

“…Plethysmography pressure changes were measured using a Validyne DP45 differential pressure transducer, CD15 carrier demodulator and a reference chamber, and were recorded with LabChart Pro in real time. Respiratory waveforms were analyzed by the BASSPRO module of the Breathe Easy software to determine respiratory frequency (V f ), tidal volume (V T ), minute ventilation (V E ), oxygen consumption (V O2 ) and ventilatory equivalents for oxygen (V E /V O2 ) (Lusk et al, 2022 ). A power analysis was performed using the reported effect size in Abbott et al (2014) which used the same mouse model as we used here and 5-13 mice were necessary to observe a statistically significant result (Abbott et al (2014) was able to see a significant difference between two groups with n=7 mice).…”