CircadiPy: An open-source toolkit for analyzing chronobiology time series.

BACKGROUND: Chronobiology is the scientific field focused on studying periodicity in biological processes. In mammals, most physiological variables exhibit circadian rhythmicity, such as metabolism, body temperature, locomotor activity, and sleep. The biological rhythmicity can be statistically evaluated by examining the time series and extracting parameters that correlate to the period of oscillation, its amplitude, phase displacement, and overall variability. NEW METHOD: We have developed a library called CircadiPy, which encapsulates methods for chronobiological analysis and data inspection, serving as an open-access toolkit for the analysis and interpretation of chronobiological data. The package was designed to be flexible, comprehensive and scalable in order to assist research dealing with processes affected or influenced by rhythmicity. RESULTS: The results demonstrate the toolkit's capability to guide users in analyzing chronobiological data collected from various recording sources, while also providing precise parameters related to the circadian rhythmicity. COMPARISON WITH EXISTING METHODS: The analysis methodology from this proposed library offers an opportunity to inspect and obtain chronobiological parameters in a straightforward and cost-free manner, in contrast to commercial tools. CONCLUSIONS: Moreover, being an open-source tool, it empowers the community with the opportunity to contribute with new functions, analysis methods, and graphical visualizations given the simplified computational method of time series data analysis using an easy and comprehensive pipeline within a single Python object.

From molecules to behavior and the clinic: Integration in chronobiology.

Chronobiology, especially the study of circadian rhythms, provides a model scientific field in which philosophers can study how investigators from a variety of disciplines working at different levels of organization are each contributing to a multi-level account of the responsible mechanism. I focus on how the framework of mechanistic explanation integrates research designed to decompose the mechanism with efforts directed at recomposition that relies especially on computation models. I also examine how recently the integration has extended beyond basic research to the processes through which the disruption of circadian rhythms contributes to disease, including various forms of cancer. Understanding these linkages has been facilitated by discoveries about how circadian mechanisms interact with mechanisms involved in other physiological processes, including the cell cycle and the immune system.

TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Time-Series Data in Circadian Biology Research.

The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms' performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.

Introduction to Chronobiology.

A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate regular environmental rhythms promotes optimal performance and survival. Herein we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s.

Sleep research goes wild: new methods and approaches to investigate the ecology, evolution and functions of sleep.

Despite being a prominent aspect of animal life, sleep and its functions remain poorly understood. As with any biological process, the functions of sleep can only be fully understood when examined in the ecological context in which they evolved. Owing to technological constraints, until recently, sleep has primarily been examined in the artificial laboratory environment. However, new tools are enabling researchers to study sleep behaviour and neurophysiology in the wild. Here, we summarize the various methods that have enabled sleep researchers to go wild, their strengths and weaknesses, and the discoveries resulting from these first steps outside the laboratory. The initial studies to 'go wild' have revealed a wealth of interindividual variation in sleep, and shown that sleep duration is not even fixed within an individual, but instead varies in response to an assortment of ecological demands. Determining the costs and benefits of this inter- and intraindividual variation in sleep may reveal clues to the functions of sleep. Perhaps the greatest surprise from these initial studies is that the reduction in neurobehavioural performance resulting from sleep loss demonstrated in the laboratory is not an obligatory outcome of reduced sleep in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.

Methods in field chronobiology.

Chronobiological research has seen a continuous development of novel approaches and techniques to measure rhythmicity at different levels of biological organization from locomotor activity (e.g. migratory restlessness) to physiology (e.g. temperature and hormone rhythms, and relatively recently also in genes, proteins and metabolites). However, the methodological advancements in this field have been mostly and sometimes exclusively used only in indoor laboratory settings. In parallel, there has been an unprecedented and rapid improvement in our ability to track animals and their behaviour in the wild. However, while the spatial analysis of tracking data is widespread, its temporal aspect is largely unexplored. Here, we review the tools that are available or have potential to record rhythms in the wild animals with emphasis on currently overlooked approaches and monitoring systems. We then demonstrate, in three question-driven case studies, how the integration of traditional and newer approaches can help answer novel chronobiological questions in free-living animals. Finally, we highlight unresolved issues in field chronobiology that may benefit from technological development in the future. As most of the studies in the field are descriptive, the future challenge lies in applying the diverse technologies to experimental set-ups in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.

Data graphs and mechanistic explanation.

It is a widespread assumption in philosophy of science that representations of data are not explanatory-that they are mere stepping stones towards an explanation, such as a representation of a mechanism. I draw on instances of representational and explanatory practice from mammalian chronobiology to suggest that this assumption is unsustainable. In many instances, biologists employ representations of data in explanatory ways that are not reducible to constraints on or evidence for representations of mechanisms. Data graphs are used to represent relationships between quantities across conditions, and often these representations are necessary for explaining particular aspects of the phenomena under study. The benefit of the analysis is two-fold. First, it provides a more accurate account of explanatory practice in broadly mechanistic investigation in biology. Second, it suggests that there is not an explanatorily "fundamental" type of representation in biology. Rather, the practice of explanation consists in the construction of different types of representations and their employment for distinct explanatory purposes.

Phenotyping Circadian Rhythms in Mice.

Circadian rhythms take place with a periodicity of 24 hr, temporally following the rotation of the earth around its axis. Examples of circadian rhythms are the sleep/wake cycle, feeding, and hormone secretion. Light powerfully entrains the mammalian clock and assists in keeping animals synchronized to the 24-hour cycle of the earth by activating specific neurons in the "central pacemaker" of the brain, the suprachiasmatic nucleus. Absolute periodicity of an animal can deviate slightly from 24 hr as manifest when an animal is placed into constant dark or "free-running" conditions. Simple measurements of an organism's activity in free-running conditions reveal its intrinsic circadian period. Mice are a particularly useful model for studying circadian rhythmicity due to the ease of genetic manipulation, thus identifying molecular contributors to rhythmicity. Furthermore, their small size allows for monitoring locomotion or activity in their homecage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are presented here including the process of entrainment, determination of tau (period length) in free-running conditions, determination of circadian periodicity in response to light disruption (e.g., jet lag studies), and evaluation of clock plasticity in non-24-hour conditions (T-cycles). Studying the properties of circadian periods such as their phase, amplitude, and length in response to photic perturbation, can be particularly useful in understanding how humans respond to jet lag, night shifts, rotating shifts, or other transient or chronic disruption of environmental surroundings.

Cronobiología del sistema inmune / Immune system chronobiology

La cronobiología es la disciplina que ha estudiado la organización temporal de los procesos que ocurren en los seres vivos, los mecanismos que las originan y sus alteraciones. En 1832, Agustín de Candolle demostró que bajo condiciones constantes el período de los ciclos de movimientos de las plantas duraba unas 24 horas, con lo que añadió una evidencia de la naturaleza endógena de los ritmos biológicos. En los mamíferos, se ha estimado que aproximadamente el 10 por ciento del genoma está bajo un control circadiano. Desde la década de los años 70´s se observó que la respuesta inmune dependía de la hora del día en la cual se analizaba y que la susceptibilidad a las infecciones dependía también de la hora en la cual el organismo fuera infectado. Recientemente se ha establecido una relación entre el ciclo circadiano y la respuesta inmune. Este trabajo trata las ventajas del conocimiento del ritmo circadiana de los mecanismos inmunitarios y la importancia del uso de la cronoterapia sobre los osciladores de las células del sistema inmune en los trastornos inmunitarios, lo cual pudiera evitar complicaciones en los pacientes(AU)

Chronobiology is the science that studies temporary organization of the processes that happen in organisms, the mechanisms that originate them and its disorders. Austin of Candolle demonstrated that under constant conditions the period of the cycles of the plants' movements it lasted some 24 hour, adding an evidence of the endogenous nature of the biological rhythms in 1832. In mammals, has been considered approximately 10 percent of genome under circadian control. Since decade of 70´s, was observed that immune response depends of day´s hours in which it was analyzed, and the susceptibility to infections also depends of the hour in which an organism is infected. It has begun to establish relationship between circadian cycle and immune response recently. This work intends to give us the advantages of the knowledge of circadian rhythms of immune mechanisms and the importance of the chronotherapy´s use on the oscillators of the immune system´s cells in immunity dysfunctions and it would avoid complications in the patients(AU)

Perception of intersensory synchrony: a tutorial review.

For most multisensory events, observers perceive synchrony among the various senses (vision, audition, touch), despite the naturally occurring lags in arrival and processing times of the different information streams. A substantial amount of research has examined how the brain accomplishes this. In the present article, we review several key issues about intersensory timing, and we identify four mechanisms of how intersensory lags might be dealt with: by ignoring lags up to some point (a wide window of temporal integration), by compensating for predictable variability, by adjusting the point of perceived synchrony on the longer term, and by shifting one stream directly toward the other.