Gadegaardcarey8465

The brain networks undergo functional reorganization across the whole lifespan, but the dynamic patterns behind the reorganization remain largely unclear. This study models the dynamics of spontaneous activity of large-scale networks using hidden Markov model (HMM), and investigates how it changes with age on two adult lifespan datasets of 176/157 subjects (aged 20-80 years). Results for both datasets showed that 1) older adults tended to spend less time on a state where default mode network (DMN) and attentional networks show antagonistic activity, 2) older adults spent more time on a "baseline" state with moderate-level activation of all networks, accompanied with lower transition probabilities from this state to the others and higher transition probabilities from the others to this state, and 3) HMM exhibited higher sensitivity in uncovering the age effects compared with temporal clustering method. Our results suggest that the aging brain is characterized by the shortening of the antagonistic instances between DMN and attention systems, as well as the prolongation of the inactive period of all networks, which might reflect the shift of the dynamical working point near criticality in older adults.

Accurate assembly of RNA-seq is a crucial step in many analytic tasks such as gene annotation or expression studies. Despite ongoing research, progress on traditional single sample assembly has brought no major breakthrough. Multi-sample RNA-Seq experiments provide more information than single sample datasets and thus constitute a promising area of research. Yet, this advantage is challenging to utilize due to the large amount of accumulating errors.

We present an extension to Ryūtō enabling the reconstruction of consensus transcriptomes from multiple RNA-seq data sets, incorporating consensus calling at low level features. We report stable improvements already at 3 replicates. Ryūtō outperforms competing approaches, providing a better and user-adjustable sensitivity-precision trade-off. Ryūtō's unique ability to utilize a (incomplete) reference for multi sample assemblies greatly increases precision. We demonstrate benefits for differential expression analysis.

Ryūtō consistently improves assembly on replicates of the same tissue independent of filter settings, even when mixing conditions or time series. Consensus voting in Ryūtō is especially effective at high precision assembly, while Ryūtō's conventional mode can reach higher recall.

Ryūtō is available at https//github.com/studla/RYUTO.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy.Healthy aging is typically associated with some level of cognitive decline, but there is substantial variation in such decline among older adults. The mechanisms behind such heterogeneity remain unclear but some have suggested a role for cognitive reserve. In this work, we propose the "person-based similarity index" for cognition (PBSI-Cog) as a proxy for cognitive reserve in older adults, and use the metric to quantify similarity between the cognitive profiles of healthy older and younger participants. In the current study, we computed this metric in 237 healthy older adults (55-88 years) using a reference group of 156 younger adults (18-39 years) taken from the Cambridge Center for Ageing and Neuroscience dataset. Our key findings revealed that PBSI-Cog scores in older adults were 1) negatively associated with age (rho = -0.25, P = 10-4) and positively associated with higher education (t = 2.4, P = 0.02), 2) largely explained by fluid intelligence and executive function, and 3) predicted more by functional connectivity between lower- and higher-order resting-state networks than brain structural morphometry or education. Particularly, we found that higher segregation between the sensorimotor and executive networks predicted higher PBSI-Cog scores. Our results support the notion that brain network functional organization may underly variability in cognitive reserve in late adulthood.

Identifying histone tail modifications using ChIP-seq is commonly used in time-series experiments in development and disease. These assays, however, cover specific time-points leaving intermediate or early stages with missing information. Although several machine learning methods were developed to predict histone marks, none exploited the dependence that exists in time-series experiments between data generated at specific time-points to extrapolate these findings to time-points where data cannot be generated for lack or scarcity of materials (i.e., early developmental stages).

Here, we train a deep learning model named TempoMAGE, to predict the presence or absence of H3K27ac in open chromatin regions by integrating information from sequence, gene expression, chromatin accessibility and the estimated change in H3K27ac state from a reference time-point. We show that adding reference time-point information systematically improves the overall model's performance. Additionally, sequence signatures extracted from our method were exclusive to the training dataset indicating that our model learned data-specific features. As an application, TempoMAGE was able to predict the activity of enhancers from pre-validated in-vivo dataset highlighting its ability to be used for functional annotation of putative enhancers.

TempoMAGE is freely available through GitHub at https//github.com/pkhoueiry/TempoMAGE.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.As source of sensory information, the body provides a sense of agency and self/non-self-discrimination. The integration of bodily states and sensory inputs with prior beliefs has been linked to the generation of bodily self-consciousness. The ability to detect surprising tactile stimuli is essential for the survival of an organism and for the formation of mental body representations. Despite the relevance for a variety of psychiatric disorders characterized by altered body and self-perception, the neurobiology of these processes is poorly understood. We therefore investigated the effect of psilocybin (Psi), known to induce alterations in self-experience, on tactile mismatch responses by combining pharmacological manipulations with simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) recording. Psi reduced activity in response to tactile surprising stimuli in frontal regions, the visual cortex, and the cerebellum. Furthermore, Psi reduced tactile mismatch negativity EEG responses at frontal electrodes, associated with alterations of body- and self-experience. This study provides first evidence that Psi alters the integration of tactile sensory inputs through aberrant prediction error processing and highlights the importance of the 5-HT2A system in tactile deviancy processing as well as in the integration of bodily and self-related stimuli. These findings may have important implications for the treatment of psychiatric disorders characterized by aberrant bodily self-awareness.

Log rank test is a widely used test that serves to assess the statistical significance of observed differences in survival, when comparing two or more groups. The log rank test is based on several assumptions that support the validity of the calculations. It is naturally assumed, implicitly, that no errors occur in the labeling of the samples. That is - that the mapping between samples and groups is perfectly correct. In this work we investigate how test results may be affected when considering some errors in the original labeling.

We introduce and define the uncertainty that arises from labeling errors in log rank test. In order to deal with this uncertainty, we develop a novel algorithm for efficiently calculating a stability interval around the original log rank p-value and prove its correctness. We demonstrate our algorithm on several datasets.

We provide a Python implementation, called LoRSI, for calculating the stability interval using our algorithm. https//github.com/YakhiniGroup/LoRSI.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

Probabilistic Identification of bacterial essential genes using TraDIS data based on Tn5 libraries has received relatively little attention in the literature; most methods are designed for mariner transposon insertions. Analysis of Tn5 transposon-based genomic data is challenging due to the high insertion density and genomic resolution. We present a novel probabilistic Bayesian approach for classifying bacterial essential genes using transposon insertion density derived from transposon insertion sequencing data. We implement a Markov chain Monte Carlo sampling procedure to estimate the posterior probability that any given gene is essential. We implement a Bayesian decision theory approach to selecting essential genes. We assess the effectiveness of our approach via analysis of both simulated data and three previously published Escherichia coli, Salmonella Typhimurium and Staphylococcus aureus datasets. These three bacteria have relatively well characterised essential genes which allows us to test our classification procedure using receiver operating characteristic curves and area under the curves. We compare the classification performance with that of Bio-Tradis, a standard tool for bacterial gene classification.

Our method is able to classify genes in the three datasets with areas under the curves between 0.967 and 0.983. Onvansertib manufacturer Our simulated synthetic datasets show that both the number of insertions and the extent to which insertions are tolerated in the distal regions of essential genes are both important in determining classification accuracy. Importantly our method gives the user the option of classifying essential genes based on the user-supplied costs of false discovery and false non-discovery.

An R package that implements the method presented in this paper is available for download from https//github.com/Kevin-walters/insdens.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.