Gales, A. | bioRxiv Science

bioRxiv2025

EEG Signature of Idiopathic Hypersomnia: Insights from Sleep Microarchitecture and Hypnodensity Metrics

Background and ObjectivesPatients with idiopathic hypersomnia with long sleep time (IH) report daytime hypersomnolence despite prolonged sleep time and normal sleep macrostructure. As they often have non-restorative sleep, we investigated whether the structure of their sleep is abnormal. MethodsIn polysomnography recordings from 80 IH participants and 48 controls, we quantified hypnodensity metrics across the night (macro level), periodic and aperiodic spectral properties, infraslow fluctuations of sigma power within the night (meso level), slow waves, sleep spindles and their clustering (microstructure). Multivariate machine-learning models were used to classify IH vs. control sleep. ResultsHypnodensity metrics were comparable between IH and controls, apart from more mixed wake/N1 sleep epochs in IH, and greater divergence between consecutive epochs of the same stage during NREM sleep in IH. Sigma power was increased in N2 sleep in IH and sleep spindles were more frequent and clustered. Slow wave density was higher in IH. Higher mean spindle cluster size correlated with higher Epworth Sleepiness Scale scores. Multivariate machine learning models incorporating these features achieved a balanced accuracy of 74% in distinguishing IH from controls. DiscussionWhile spindles and slow waves are typically associated with good sleep quality, they are increased in IH patients. This could reflect greater need for sleep and increased difficulty waking up in IH, which is also characterized by more mixed wake/N1 stages.

neuroscience↗

bioRxiv2018

Gene composition as a potential barrier to large recombinations in the bacterial pathogen Klebsiella pneumoniae

Klebsiella pneumoniae (Kp) is one of the most important nosocomial pathogens world-wide, being responsible for frequent hospital outbreaks and causing sepsis and multi-organ infections with a high mortality rate and frequent hospital outbreaks. The most prevalent and widely disseminated lineage of K. pneumoniae is clonal group 258 (CG258), which includes the highly resistant \"high-risk\" genotypes ST258 and ST11. Recent studies revealed that very large recombination events have occurred during the recent emergence of Kp lineages. A striking example is provided by ST258, which has undergone a recombination event that replaced over 1 Mb of the genome with DNA from an unrelated Kp donor. Although several examples of this phenomenon have been documented in Kp and other bacterial species, the significance of these very large recombination events for the emergence of either hyper-virulent or resistant clones remains unclear. Here we present an analysis of 834 Kp genomes that provides data on the frequency of these very large recombination events (defined as those involving >100Kb), their distribution within the genome, and the dynamics of gene flow within the Kp population. We note that very large recombination events occur frequently, and in multiple lineages, and that the majority of recombinational exchanges are clustered within two overlapping genomic regions, which result to be involved by recombination events with different frequencies. Our results also indicate that certain non-CG258 lineages are more likely to act as donors to CG258 recipients than others. Furthermore, comparison of gene content in CG258 and non-CG258 strains agrees with this pattern, suggesting that the success of a large recombination depends on gene composition in the exchanged genomic portion.\n\nAuthor SummaryKlebsiella pneumoniae (Kp) is an opportunistic bacterial pathogen, a major cause of deadly infections and outbreaks in hospitals worldwide. This bacterium is able to exchange large genomic portions (up to a fourth of the entire genome) within a single recombination event. Indeed, the most epidemiologically important Kp clone, is actually a hybrid which emerged after a > 1Mb recombination event. In this work, we investigated how recombinations affected the evolution of the most studied Kp Clonal Group, CG258. We found that large recombinations occurred frequently during Kp evolution, and occurred preferentially in a well-delimited genomic region. Furthermore, we found that four epidemiologically important clones emerged after large recombinations. We identified the donors of several large recombinations: despite many Kp lineages acted as donors during CG258 evolution, two of them have been involved more frequently. We hypothesize that the observed pattern of donors-recipients in recombinations, and the presence of a large recombinogenic region in Kp genome, could be related to gene composition. Indeed, genomic analyses showed a pattern compatible with this hypothesis, suggesting that gene content can represent a main factor in the success of a large recombination.

evolutionary biology↗