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Abundant epidemiological evidence links circadian rhythms to human health, from heart disease to neurodegeneration. Accurate determination of an individual’s circadian phase is critical for precision diagnostics and personalized timing of therapeutic interventions. To date, however, we still lack an assay for physiological time that is accurate, minimally burdensome to the patient, and readily generalizable to new data. Here, we present TimeMachine, an algorithm to predict the human circadian phase using gene expression in peripheral blood mononuclear cells from a single blood draw. Once trained on data from a single study, we validated the trained predictor against four independent datasets with distinct experimental protocols and assay platforms, demonstrating that it can be applied generalizably. Importantly, TimeMachine predicted circadian time with a median absolute error ranging from 1.65 to 2.7 h, regardless of systematic differences in experimental protocol and assay platform, without renormalizing the data or retraining the predictor. This feature enables it to be flexibly applied to both new samples and existing data without limitations on the transcriptomic profiling technology (microarray, RNAseq). We benchmark TimeMachine against competing approaches and identify the algorithmic features that contribute to its performance. 

Abstract University faculty hiring networks are known to be hierarchical and to exacerbate various types of inequity. Still, a detailed, historical understanding of hiring dynamics lacks in many academic fields. We focus on the field of mathematics, analyzing over 120,000 records from 150 institutions over seven decades to elucidate the temporal dynamics of hiring doctoral-granting (DG) faculty at the individual and departmental levels. We demonstrate that the disparity between the number of mathematics Ph.D.s awarded and the number of DG faculty positions filled has grown over time. Even institutions with the best records of DG faculty placement have experienced a temporal decline in the probability of their graduates obtaining a DG faculty position. By quantifying the mathematical prestige of each department with a network statistic, authority centrality, we find an approximately linear relationship between the log of the prestige of one’s Ph.D. institution and the log of the probability of obtaining a faculty position. Moreover, we observe associations suggesting that the probability of DG faculty placement has decreased over time and is smaller for women than for men. On the departmental level, a group of 14 elite departments dominated the authority centrality of the entire network between 1950 and 2019. Strikingly, one department within this elite group increased its centrality scores consistently, which hints at the possibility for a department to improve its prestige. This analysis highlights the challenges of transitioning from Ph.D. holder to faculty member in mathematics. 

Which suggestions for behavioral modifications, based on mathematical models, are most likely to be followed in the real world? We address this question in the context of human circadian rhythms. Jet lag is a consequence of the misalignment of the body’s internal circadian (~24-hour) clock during an adjustment to a new schedule. Light is the clock’s primary synchronizer. Previous research has used mathematical models to compute light schedules that shift the circadian clock to a new time zone as quickly as possible. How users adjust their behavior when provided with these optimal schedules remains an open question. Here, we report data collected by wearables from more than 100 travelers as they cross time zones using a smartphone app, Entrain . We find that people rarely follow the optimal schedules generated through mathematical modeling entirely, but travelers who better followed the optimal schedules reported more positive moods after their trips. Using the data collected, we improve the optimal schedule predictions to accommodate real-world constraints. We also develop a scheduling algorithm that allows for the computation of approximately optimal schedules "on-the-fly" in response to disruptions. User burnout may not be critically important as long as the first parts of a schedule are followed. These results represent a crucial improvement in making the theoretical results of past work viable for practical use and show how theoretical predictions based on known human physiology can be efficiently used in real-world settings. 

Abstract From smart work scheduling to optimal drug timing, there is enormous potential in translating circadian rhythms research results for precision medicine in the real world. However, the pursuit of such effort requires the ability to accurately estimate circadian phase outside of the laboratory. One approach is to predict circadian phase noninvasively using light and activity measurements and mathematical models of the human circadian clock. Most mathematical models take light as an input and predict the effect of light on the human circadian system. However, consumer-grade wearables that are already owned by millions of individuals record activity instead of light, which prompts an evaluation of the accuracy of predicting circadian phase using motion alone. Here, we evaluate the ability of four different models of the human circadian clock to estimate circadian phase from data acquired by wrist-worn wearable devices. Multiple datasets across populations with varying degrees of circadian disruption were used for generalizability. Though the models we test yield similar predictions, analysis of data from 27 shift workers with high levels of circadian disruption shows that activity, which is recorded in almost every wearable device, is better at predicting circadian phase than measured light levels from wrist-worn devices when processed by mathematical models. In those living under normal living conditions, circadian phase can typically be predicted to within 1 h, even with data from a widely available commercial device (the Apple Watch). These results show that circadian phase can be predicted using existing data passively collected by millions of individuals with comparable accuracy to much more invasive and expensive methods.