scholarly journals Quantifying information accumulation encoded in the dynamics of biochemical signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ying Tang ◽  
Adewunmi Adelaja ◽  
Felix X.-F. Ye ◽  
Eric Deeds ◽  
Roy Wollman ◽  
...  
Keyword(s):  
Time Course ◽  
Environmental Changes ◽  
Signaling Proteins ◽  
Combinatorial Explosion ◽  
Transcriptional Dynamics ◽  
Signaling Dynamics ◽  
Cellular Decision Making ◽  
Negative Feedback Circuit ◽  
Over Time ◽  
Specific Phase

AbstractCellular responses to environmental changes are encoded in the complex temporal patterns of signaling proteins. However, quantifying the accumulation of information over time to direct cellular decision-making remains an unsolved challenge. This is, in part, due to the combinatorial explosion of possible configurations that need to be evaluated for information in time-course measurements. Here, we develop a quantitative framework, based on inferred trajectory probabilities, to calculate the mutual information encoded in signaling dynamics while accounting for cell-cell variability. We use it to understand NFκB transcriptional dynamics in response to different immune threats, and reveal that some threats are distinguished faster than others. Our analyses also suggest specific temporal phases during which information distinguishing threats becomes available to immune response genes; one specific phase could be mapped to the functionality of the IκBα negative feedback circuit. The framework is generally applicable to single-cell time series measurements, and enables understanding how temporal regulatory codes transmit information over time.

scholarly journals Temporal transcriptomic profiling reveals dynamic changes in gene expression of Xenopus animal cap upon activin treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumeko Satou-Kobayashi ◽  
Jun-Dal Kim ◽  
Akiyoshi Fukamizu ◽  
Makoto Asashima
Keyword(s):  
Time Course ◽  
Transforming Growth Factor ◽  
Transcriptome Profiling ◽  
Transforming Growth Factor Β ◽  
Activin A ◽  
Cytokine Signaling ◽  
Molecular Characteristics ◽  
Transcriptional Dynamics

AbstractActivin, a member of the transforming growth factor-β (TGF-β) superfamily of proteins, induces various tissues from the amphibian presumptive ectoderm, called animal cap explants (ACs) in vitro. However, it remains unclear how and to what extent the resulting cells recapitulate in vivo development. To comprehensively understand whether the molecular dynamics during activin-induced ACs differentiation reflect the normal development, we performed time-course transcriptome profiling of Xenopus ACs treated with 50 ng/mL of activin A, which predominantly induced dorsal mesoderm. The number of differentially expressed genes (DEGs) in response to activin A increased over time, and totally 9857 upregulated and 6663 downregulated DEGs were detected. 1861 common upregulated DEGs among all Post_activin samples included several Spemann’s organizer genes. In addition, the temporal transcriptomes were clearly classified into four distinct groups in correspondence with specific features, reflecting stepwise differentiation into mesoderm derivatives, and a decline in the regulation of nuclear envelop and golgi. From the set of early responsive genes, we also identified the suppressor of cytokine signaling 3 (socs3) as a novel activin A-inducible gene. Our transcriptome data provide a framework to elucidate the transcriptional dynamics of activin-driven AC differentiation, reflecting the molecular characteristics of early normal embryogenesis.

scholarly journals Jonckheere–Terpstra–Kendall-based non-parametric analysis of temporal differential gene expression

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Hitoshi Iuchi ◽  
Michiaki Hamada
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Time Course ◽  
Time Series Data ◽  
Expression Patterns ◽  
Detection Methods ◽  
Series Data ◽  
Expression Levels ◽  
Over Time ◽  
Non Parametric

Abstract Time-course experiments using parallel sequencers have the potential to uncover gradual changes in cells over time that cannot be observed in a two-point comparison. An essential step in time-series data analysis is the identification of temporal differentially expressed genes (TEGs) under two conditions (e.g. control versus case). Model-based approaches, which are typical TEG detection methods, often set one parameter (e.g. degree or degree of freedom) for one dataset. This approach risks modeling of linearly increasing genes with higher-order functions, or fitting of cyclic gene expression with linear functions, thereby leading to false positives/negatives. Here, we present a Jonckheere–Terpstra–Kendall (JTK)-based non-parametric algorithm for TEG detection. Benchmarks, using simulation data, show that the JTK-based approach outperforms existing methods, especially in long time-series experiments. Additionally, application of JTK in the analysis of time-series RNA-seq data from seven tissue types, across developmental stages in mouse and rat, suggested that the wave pattern contributes to the TEG identification of JTK, not the difference in expression levels. This result suggests that JTK is a suitable algorithm when focusing on expression patterns over time rather than expression levels, such as comparisons between different species. These results show that JTK is an excellent candidate for TEG detection.

Decomposition of Growth Curves into Growth Rate and Acceleration: a Novel Procedure to Monitor Bacterial Growth and the Time-Dependent Effect of Antimicrobials

2021 ◽  
Author(s):  
M. Luisa Navarro-Pérez ◽  
M. Coronada Fernández-Calderón ◽  
Virginia Vadillo-Rodríguez
Keyword(s):  
Growth Rate ◽  
Mathematical Models ◽  
Bacterial Growth ◽  
Time Course ◽  
Antimicrobial Agents ◽  
Numerical Procedure ◽  
Growth Curves ◽  
Predictive Microbiology ◽  
Insight Into ◽  
Over Time

In this paper, a simple numerical procedure is presented to monitor the growth of Streptococcus sanguinis over time in the absence and presence of propolis, a natural antimicrobial. In particular, it is shown that the real-time decomposition of growth curves obtained through optical density measurements into growth rate and acceleration can be a powerful tool to precisely assess a large range of key parameters [ i.e. lag time ( t 0 ), starting growth rate ( γ 0 ), initial acceleration of the growth ( a 0 ), maximum growth rate ( γ max ), maximum acceleration ( a max ) and deceleration ( a min ) of the growth and the total number of cells at the beginning of the saturation phase ( N s )] that can be readily used to fully describe growth over time. Consequently, the procedure presented provides precise data of the time course of the different growth phases and features, which is expected to be relevant, for instance, to thoroughly evaluate the effect of new antimicrobial agents. It further provides insight into predictive microbiology, likely having important implications to assumptions adopted in mathematical models to predict the progress of bacterial growth. Importance: The new and simple numerical procedure presented in this paper to analyze bacterial growth will possibly allow identifying true differences in efficacy among antimicrobial drugs for their applications in human health, food security, and environment, among others. It further provides insight into predictive microbiology, likely helping in the development of proper mathematical models to predict the course of bacterial growth under diverse circumstances.

Sleep Disorder Over Time: Psychiatric Correlates Among Males

1980 ◽  
Vol 136 (5) ◽  
pp. 456-462 ◽  
Author(s):  
Hervey Sweetwood ◽  
Igor Grant ◽  
Daniel F. Kripke ◽  
Marvin S. Gerst ◽  
Joel Yager
Keyword(s):  
Prospective Study ◽  
Sleep Disorder ◽  
Sleep Disturbances ◽  
Time Course ◽  
Psychiatric Symptomatology ◽  
Over Time

SummaryThis 18 month prospective study assessed the time course of sleep disturbances in 85 male psychiatric out-patients and 103 male non-patients. Over one-third of the patients and 5 per cent of the non-patients reported frequent symptoms of insomnia during at least 14 of the 18 months. Frequency and chronicity of insomnia were strongly associated with intensity of psychiatric symptomatology, but not with diagnosis. Minor tranquillizers and hypnotics were used frequently by patients and occasionally by non-patients, but there was little indication that they altered the course of insomnia.

scholarly journals Temporal Dynamics of Cloacal Microbiota in Adult Laying Chickens With and Without Access to an Outdoor Range

2021 ◽  
Vol 11 ◽  
Author(s):  
Janneke Schreuder ◽  
Francisca C. Velkers ◽  
Alex Bossers ◽  
Ruth J. Bouwstra ◽  
Willem F. de Boer ◽  
...  
Keyword(s):  
Microbial Community ◽  
Community Composition ◽  
Intestinal Microbiota ◽  
Environmental Changes ◽  
Temporal Dynamics ◽  
Microbial Community Composition ◽  
Sudden Change ◽  
Rrna Gene ◽  
Poultry House ◽  
Over Time

Associations between animal health and performance, and the host’s microbiota have been recently established. In poultry, changes in the intestinal microbiota have been linked to housing conditions and host development, but how the intestinal microbiota respond to environmental changes under farm conditions is less well understood. To gain insight into the microbial responses following a change in the host’s immediate environment, we monitored four indoor flocks of adult laying chickens three times over 16 weeks, during which two flocks were given access to an outdoor range, and two were kept indoors. To assess changes in the chickens’ microbiota over time, we collected cloacal swabs of 10 hens per flock and performed 16S rRNA gene amplicon sequencing. The poultry house (i.e., the stable in which flocks were housed) and sampling time explained 9.2 and 4.4% of the variation in the microbial community composition of the flocks, respectively. Remarkably, access to an outdoor range had no detectable effect on microbial community composition, the variability of microbiota among chickens of the same flock, or microbiota richness, but the microbiota of outdoor flocks became more even over time. Fluctuations in the composition of the microbiota over time within each poultry house were mainly driven by turnover in rare, rather than dominant, taxa and were unique for each flock. We identified 16 amplicon sequence variants that were differentially abundant over time between indoor and outdoor housed chickens, however none were consistently higher or lower across all chickens of one housing type over time. Our study shows that cloacal microbiota community composition in adult layers is stable following a sudden change in environment, and that temporal fluctuations are unique to each flock. By exploring microbiota of adult poultry flocks within commercial settings, our study sheds light on how the chickens’ immediate environment affects the microbiota composition.

scholarly journals Intricate genetic programs controlling dormancy in Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Abrar A. Abidi ◽  
Eliza J. R. Peterson ◽  
Mario L. Arrieta-Ortiz ◽  
Boris Aguilar ◽  
James T. Yurkovich ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Time Course ◽  
Experimental System ◽  
Topology Analysis ◽  
Transcriptional Dynamics ◽  
Regulatory Circuits ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Location Map ◽  
Favorable Conditions

AbstractMycobacterium tuberculosis (MTB), responsible for the deadliest infectious disease worldwide, displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and opportunistically exploit immunocompromised individuals. Uncovering the gene regulatory programs that underlie the dramatic phenotypic shifts in MTB during disease latency and reactivation has posed an extraordinary challenge. We developed a novel experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the chain of transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding location map and insights from network topology analysis, we identified regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions.One Sentence SummaryHigh-resolution transcriptional time-course reveals six-state genetic program that enables MTB to enter and exit hypoxia-induced dormancy.

scholarly journals Predicting context specific enhancer-promoter interactions from ChIP-Seq time course data

2017 ◽  
Author(s):  
Tomasz Dzida ◽  
Mudassar Iqbal ◽  
Iryna Charapitsa ◽  
George Reid ◽  
Henk Stunnenberg ◽  
...  
Keyword(s):  
Estrogen Receptor Alpha ◽  
Time Course ◽  
Target Genes ◽  
Mcf7 Cells ◽  
Genome Wide ◽  
A Genome ◽  
Machine Learning Approach ◽  
Protein Occupancy ◽  
Context Specific ◽  
Over Time

We have developed a machine learning approach to predict context specific enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ERα binding. We use the method to identify a genome-wide confident set of ERα target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ERα binding proximity alone.

scholarly journals An adaptive system for autonomous driving

2020 ◽  
Vol 28 (3) ◽  
pp. 1189-1212
Author(s):  
Martin Zimmermann ◽  
Franz Wotawa
Keyword(s):  
Adaptive Control ◽  
Automotive Industry ◽  
Environmental Conditions ◽  
Environmental Changes ◽  
Adaptive System ◽  
Control Method ◽  
Autonomous Driving ◽  
Optimal Selection ◽  
Safe State ◽  
Over Time

Abstract Having systems that can adapt themselves in case of faults or changing environmental conditions is of growing interest for industry and especially for the automotive industry considering autonomous driving. In autonomous driving, it is vital to have a system that is able to cope with faults in order to enable the system to reach a safe state. In this paper, we present an adaptive control method that can be used for this purpose. The method selects alternative actions so that given goal states can be reached, providing the availability of a certain degree of redundancy. The action selection is based on weight models that are adapted over time, capturing the success rate of certain actions. Besides the method, we present a Java implementation and its validation based on two case studies motivated by the requirements of the autonomous driving domain. We show that the presented approach is applicable both in case of environmental changes but also in case of faults occurring during operation. In the latter case, the methods provide an adaptive behavior very much close to the optimal selection.

Intracranial Pressure Time Course in Primary Intracerebral Hemorrhage

Neurosurgery ◽  
1979 ◽  
Vol 4 (6) ◽  
pp. 504-511 ◽  
Author(s):  
Isacco Papo ◽  
Pierre Janny ◽  
Giuseppe Caruselli ◽  
Gilles Colnet ◽  
Antonio Luongo
Keyword(s):  
Intracranial Pressure ◽  
Time Course ◽  
Elevated Pressure ◽  
Deep Coma ◽  
Postoperative Course ◽  
Disturbance Of Consciousness ◽  
Pressure Time ◽  
Intermediate Disturbances ◽  
Over Time ◽  
Definite Correlation

abstract The course of intracranial pressure (ICP) over time was studied in 66 hypertensive and/or atherosclerotic patients harboring intracerebral hematomas. Patients with no disturbance of consciousness showed normal or only slightly elevated pressure. Conversely, most patients in deep coma exhibited high pressure with a tendency to rise further no matter what treatment was used. In the remaining patients with intermediate disturbances of consciousness, no definite correlation was found between ICP, clinical condition, and outcome. In all of the patients who underwent operation, the postoperative course of ICP over time was also studied and seemed to depend to a certain extent on the timing of the operation.

125 Transcriptomic changes in bovine ovarian cortex in response to FSH signaling

2020 ◽  
Vol 32 (2) ◽  
pp. 189
Author(s):  
J. Candelaria ◽  
B. Rabaglino ◽  
A. Denicol
Keyword(s):  
Time Course ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Signalling Pathways ◽  
Biological Functions ◽  
Cortical Cells ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
Ovarian Cortex ◽  
Over Time

Preantral follicles serve as a reservoir of female gametes that could be used in assisted reproductive technologies in humans, livestock, and endangered animals. Invitro culture of ovarian cortex is a widely used method to grow preantral follicles. Follicle-stimulating hormone (FSH) is often added to the culture medium as a folliculogenesis-promoting factor. The roles of FSH in antral follicles is well known; however, the effects of FSH in preantral follicles and indirectly in the ovarian cortical cells is largely unknown. The aim of this study was to determine the transcriptomic responses of the ovarian cortex containing preantral follicles to FSH signalling over time. In 3 biological replicates, small strips of bovine ovarian cortex (10×5mm) were dissected from the medulla and evaluated under a stereomicroscope for removal of all visible antral follicles. Resulting cortical strips were cultured in defined medium with human-recombinant FSH or vehicle for 2 or 4 days at 38.5°C and 5% CO2. The RNA was isolated and subjected to cDNA library preparation and 3′-Tag RNA sequencing. Sequencing data analysis was performed using the edgeR and maSigPro packages (Bioconductor-R). Using a time-course analysis, genes up- or downregulated 2-fold or more and associated with an FDR<0.05 were considered differentially expressed (DEG) and were further analysed with NetworkAnalyst software. We found 252 DEG over time in response to FSH. In FSH-treated samples, significantly enriched biological functions from upregulated genes were associated with glycolysis, gluconeogenesis, carbon metabolism, and biosynthesis of amino acids. In contrast, significantly enriched biological functions from downregulated genes found in FSH-treated samples included phagosome and necroptosis. The germ cell markers BMP15, DAZL, DDX4, GDF9, and ZP2/ZP3 were expressed but unchanged by FSH, suggesting the presence of similar numbers of oocytes between samples. The gene B4GALT2, previously reported as a granulosa cell marker, was upregulated in FSH-treated samples at Day 4. The follicular marker RAB23 was expressed in all samples and not changed by FSH. One interesting finding was upregulation of MAPK signalling (represented by the genes MAPKAPK3, ELK4, MKNK2, and TGFB3) in response to FSH signalling, with no change in expression of the cAMP-response element responsive genes CYP19A1 and INHA. Together, these data indicate that FSH stimulates energy metabolism in ovarian cortical cells and represses negative cell function activity. We conclude that these responses are mostly mediated by granulosa cells, because the FSH receptor is not appreciably expressed in the ovarian cortex stroma. Moreover, the data suggest that FSH may utilise alternative signalling pathways, such as MAPK, in early follicles. This information enhances our understanding of FSH signalling pathways in the ovarian cortex, mediated by preantral follicles to create a positive environment for folliculogenesis.

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