TimeTeller: A tool to probe the circadian clock as a multigene dynamical system.

Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including cancer and heart diseases. Therefore, there is a need for tools to measure the functional state of the molecular circadian clock and its downstream targets in patients. Moreover, the clock is a multi-dimensional stochastic oscillator and there are few tools for analysing it as a noisy multigene dynamical system. In this paper we consider the methodology behind TimeTeller, a machine learning tool that analyses the clock as a noisy multigene dynamical system and aims to estimate circadian clock function from a single transcriptome by modelling the multi-dimensional state of the clock. We demonstrate its potential for clock systems assessment by applying it to mouse, baboon and human microarray and RNA-seq data and show how to visualise and quantify the global structure of the clock, quantitatively stratify individual transcriptomic samples by clock dysfunction and globally compare clocks across individuals, conditions and tissues thus highlighting its potential relevance for advancing circadian medicine.

Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection.

Sleep and circadian rhythm disruption (SCRD), as encountered during shift work, increases the risk of respiratory viral infection including SARS-CoV-2. However, the mechanism(s) underpinning higher rates of respiratory viral infection following SCRD remain poorly characterized. To address this, we investigated the effects of acute sleep deprivation on the mouse lung transcriptome. Here we show that sleep deprivation profoundly alters the transcriptional landscape of the lung, causing the suppression of both innate and adaptive immune systems, disrupting the circadian clock, and activating genes implicated in SARS-CoV-2 replication, thereby generating a lung environment that could promote viral infection and associated disease pathogenesis. Our study provides a mechanistic explanation of how SCRD increases the risk of respiratory viral infections including SARS-CoV-2 and highlights possible therapeutic avenues for the prevention and treatment of respiratory viral infection.

Parameters of stochastic models for electroencephalogram data as biomarkers for child's neurodevelopment after cerebral malaria.

The objective of this study was to test statistical features from the electroencephalogram (EEG) recordings as predictors of neurodevelopment and cognition of Ugandan children after coma due to cerebral malaria. The increments of the frequency bands of EEG time series were modeled as Student processes; the parameters of these Student processes were estimated and used along with clinical and demographic data in a machine-learning algorithm for the prediction of children's neurodevelopmental and cognitive scores 6 months after cerebral malaria illness. The key innovation of this work is in the identification of stochastic EEG features that can serve as language-independent markers of the impact of cerebral malaria on the developing brain. The results can enhance prognostic determination of which children are in most need of rehabilitative interventions, which is especially important in resource-constrained settings such as sub-Saharan Africa.