Biology subjects

Khoueiry, P.

Publications and source records attributed to Khoueiry, P..

3 recordsLinked to original sources

bioRxiv2023

Bursting with potential: How sensorimotor beta bursts develop from infancy to adulthood

Beta activity is thought to play a critical role in sensorimotor processes. However, little is known about how activity in this frequency band develops. Here, we investigated the developmental trajectory of sensorimotor beta activity from infancy to adulthood. We recorded electroencephalography (EEG) from adults, 12-month-olds, and 9-month-olds while they observed and executed grasping movements. We analysed beta burst activity using a novel method that combines time-frequency decomposition and principal component analysis (PCA). We then examined the changes in burst rate and waveform motifs along the selected principal components. Our results reveal systematic changes in beta activity during action execution across development. We found a decrease in beta burst rate during movement execution in all age groups, with the greatest decrease observed in adults. Additionally, we identified four principal components that defined waveform motifs that systematically changed throughout the trial. We found that bursts with waveform shapes closer to the median waveform were not rate-modulated, whereas those with waveform shapes further from the median were differentially rate-modulated. Interestingly, the decrease in the rate of certain burst motifs occurred earlier during movement and was more lateralized in adults than in infants, suggesting that the rate modulation of specific types of beta bursts becomes increasingly refined with age.

neuroscience↗

bioRxiv2020

The hourglass model of evolutionary conservation during embryogenesis extends to developmental enhancers with signatures of positive selection

Inter-species comparisons of both morphology and gene expression within a phylum have revealed a period in the middle of embryogenesis with more similarity between species compared to earlier and later time-points. This developmental hourglass pattern has been observed in many phyla, yet the evolutionary constraints on gene expression, and underlying mechanisms of how this is regulated, remains elusive. Moreover, the role of positive selection on gene regulation in the more diverged earlier and later stages of embryogenesis remains unknown. Here, using DNase-seq to identify regulatory regions in two distant Drosophila species (D. melanogaster and D. virilis), we assessed the evolutionary conservation and adaptive evolution of enhancers throughout multiple stages of embryogenesis. This revealed a higher proportion of conserved enhancers at the phylotypic period, providing a regulatory basis for the hourglass expression pattern. Using an in silico mutagenesis approach, we detect signatures of positive selection on developmental enhancers at early and late stages of embryogenesis, with a depletion at the phylotypic period, suggesting positive selection as one evolutionary mechanism underlying the hourglass pattern of animal evolution.

evolutionary biology↗

bioRxiv2018

Evolutionary changes in DNA accessibility and sequence predict divergence of transcription factor binding and enhancer activity

Transcription factor (TF) binding is determined by sequence as well as chromatin accessibility. While the role of accessibility in shaping TF-binding landscapes is well recorded, its role in evolutionary divergence of TF binding, which in turn can alter cis-regulatory activities, is not well understood. In this work, we studied the evolution of genome-wide binding landscapes of five major transcription factors (TFs) in the core network of mesoderm specification, between D. melanogaster and D. virilis, and examined its relationship to accessibility and sequence-level changes. We generated chromatin accessibility data from three important stages of embryogenesis in both D. melanogaster and D. virilis, and recorded conservation and divergence patterns. We then used multi-variable models to correlate accessibility and sequence changes to TF binding divergence. We found that accessibility changes can in some cases, e.g., for the master regulator Twist and for earlier developmental stages, more accurately predict binding change than is possible using TF binding motif changes between orthologous enhancers. Accessibility changes also explain a significant portion of the co-divergence of TF pairs. We noted that accessibility and motif changes offer complementary views of the evolution of TF binding, and developed a combined model that captures the evolutionary data much more accurately than either view alone. Finally, we trained machine learning models to predict enhancer activity from TF binding, and used these functional models to argue that motif and accessibility-based predictors of TF binding change can substitute for experimentally measured binding change, for the purpose of predicting evolutionary changes in enhancer activity.

evolutionary biology↗