Sex differences in human adipose tissue gene expression and genetic regulation involve adipogenesis.

Sex differences in adipose tissue distribution and function are associated with sex differences in cardiometabolic disease. While many studies have revealed sex differences in adipocyte cell signaling and physiology, there is a relative dearth of information regarding sex differences in transcript abundance and regulation. We investigated sex differences in subcutaneous adipose tissue transcriptional regulation using omic-scale data from ∼3000 geographically and ethnically diverse human samples. We identified 162 genes with robust sex differences in expression. Differentially expressed genes were implicated in oxidative phosphorylation and adipogenesis. We further determined that sex differences in gene expression levels could be related to sex differences in the genetics of gene expression regulation. Our analyses revealed sex-specific genetic associations, and this finding was replicated in a study of 98 inbred mouse strains. The genes under genetic regulation in human and mouse were enriched for oxidative phosphorylation and adipogenesis. Enrichment analysis showed that the associated genetic loci resided within binding motifs for adipogenic transcription factors (e.g., PPARG and EGR1). We demonstrated that sex differences in gene expression could be influenced by sex differences in genetic regulation for six genes (e.g., FADS1 and MAP1B). These genes exhibited dynamic expression patterns during adipogenesis and robust expression in mature human adipocytes. Our results support a role for adipogenesis-related genes in subcutaneous adipose tissue sex differences in the genetic and environmental regulation of gene expression.

Analysis of respiratory kinematics: a method to characterize breaths from motion signals.

Objective.Breathing motion (respiratory kinematics) can be characterized by the interval and depth of each breath, and by magnitude-synchrony relationships between locations. Such characteristics and their breath-by-breath variability might be useful indicators of respiratory health. To enable breath-by-breath characterization of respiratory kinematics, we developed a method to detect breaths using motion sensors.Approach.In 34 volunteers who underwent maximal exercise testing, we used 8 motion sensors to record upper rib, lower rib and abdominal kinematics at 3 exercise stages (rest, lactate threshold and exhaustion). We recorded volumetric air flow signals using clinical exercise laboratory equipment and synchronized them with kinematic signals. Using instantaneous phase landmarks from the analytic representation of kinematic and flow signals, we identified individual breaths and derived respiratory rate (RR) signals at 1 Hz. To evaluate the fidelity of kinematics-derived RR, we calculated bias, limits of agreement, and cross-correlation coefficients (CCC) relative to flow-derived RR. To identify coupling between kinematics and flow, we calculated the Shannon entropy of the relative frequency with which flow landmarks were distributed over the phase of the kinematic cycle.Main Results.We found good agreement in the kinematics-derived and flow-derived RR signals [bias (95% limit of agreement) = 0.1 (± 7) breaths/minute; CCC median (IQR) = 0.80 (0.48-0.91)]. In individual signals, kinematics and flow were well-coupled (entropy 0.9-1.4 across sensors), but the relationship varied within (by exercise stage) and between individuals. The final result was that the flow landmarks did not consistently localize to any particular phase of the kinematic signals (entropy 2.2-3.0 across sensors).Significance.The Analysis of Respiratory Kinematics method can yield highly resolved respiratory rate signals by separating individual breaths. This method will facilitate characterization of clinically significant breathing motion patterns on a breath-by-breath basis. The relationship between respiratory kinematics and flow is much more complex than expected, varying between and within individuals.

GSEAplot: A Package for Customizing Gene Set Enrichment Analysis in R.

Gene Set Enrichment Analysis (GSEA) is used to identify differentially expressed gene sets that are enriched for annotated biological functions. The existing GSEA R code is not in the form of a flexible package with analysis and plotting customization options, and the results produced are not generated in the form of R objects. In this study, we introduce the GSEAplot R package with novel functionality for saving relevant information from the analysis to the current R workspace, and we introduce the ability to customize plots and databases. The GSEAplot package provides a novel utility that facilitates the implementation of GSEA R-based in genomics analysis pipelines.