Explore the vast range of titles available.

Predictions of COVID-19 case growth and mortality are critical to the decisions of political leaders, businesses, and individuals grappling with the pandemic. This predictive task is challenging due to the novelty of the virus, limited data, and dynamic political and societal responses. We embed a Bayesian time series model and a random forest algorithm within an epidemiological compartmental model for empirically grounded COVID-19 predictions. The Bayesian case model fits a location-specific curve to the velocity (first derivative) of the log transformed cumulative case count, borrowing strength across geographic locations and incorporating prior information to obtain a posterior distribution for case trajectories. The compartmental model uses this distribution and predicts deaths using a random forest algorithm trained on COVID-19 data and population-level characteristics, yielding daily projections and interval estimates for cases and deaths in U.S. states. We evaluated the model by training it on progressively longer periods of the pandemic and computing its predictive accuracy over 21-day forecasts. The substantial variation in predicted trajectories and associated uncertainty between states is illustrated by comparing three unique locations: New York, Colorado, and West Virginia. The sophistication and accuracy of this COVID-19 model offer reliable predictions and uncertainty estimates for the current trajectory of the pandemic in the U.S. and provide a platform for future predictions as shifting political and societal responses alter its course.

DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging, but their underlying principles appear to be evolutionarily conserved, as they have now been successfully developed for many mammalian species. Here, we describe reliable and highly accurate epigenetic clocks shown to apply to 93 domestic dog breeds. The methylation profiles were generated using the mammalian methylation array, which utilizes DNA sequences that are conserved across all mammalian species. Canine epigenetic clocks were constructed to estimate age and also average time to death. We also present two highly accurate human–dog dual species epigenetic clocks (R = 0.97), which may facilitate the ready translation from canine to human use (or vice versa) of antiaging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies here reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan. Overall, we describe robust biomarkers to measure aging and, potentially, health status in canines.

Cytosine methylation patterns have not yet been thoroughly studied in horses. Here, we profile n  = 333 samples from 42 horse tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). Using the blood and liver tissues from horses, we develop five epigenetic aging clocks: a multi-tissue clock, a blood clock, a liver clock and two dual-species clocks that apply to both horses and humans. In addition, using blood methylation data from three additional equid species (plains zebra, Grevy’s zebras and Somali asses), we develop another clock that applies across all equid species. Castration does not significantly impact the epigenetic aging rate of blood or liver samples from horses. Methylation and RNA data from the same tissues define the relationship between methylation and RNA expression across horse tissues. We expect that the multi-tissue atlas will become a valuable resource. Methylation levels of specific sites in the genome is correlated with aging. Here the authors develop a human-horse clock which could assist in translating anti-aging interventions from humans to horses and vice versa.

This study presents refined epigenetic clocks for cetaceans, building on previous research that estimated ages in several species from bottlenose dolphins to bowhead and humpback whales using cytosine methylation levels. We combined publicly available data (generated on the HorvathMammalMethylChip40 platform) from skin (n = 805) and blood (n = 286) samples across 13 cetacean species, aged 0 to 139 years. By combining methylation data from different sources, we enhanced our sample size, thereby strengthening the statistical validity of our clocks. We used elastic net regression with leave one sample out (LOO) and leave one species out (LOSO) cross validation to produce highly accurate blood only (Median Absolute Error [MAE] = 1.64 years, r = 0.96), skin only (MAE = 2.32 years, r = 0.94) and blood and skin multi-tissue (MAE = 2.24 years, r = 0.94) clocks. In addition, the LOSO blood and skin (MAE = 5.6 years, repeated measures r = 0.83), skin only (MAE = 6.22 years, repeated measures r = 0.81), and blood only (MAE = 4.11 years, repeated measures r = 0.95) clock analysis demonstrated relatively high correlation toward cetacean species not included within this current data set and provide evidence for a broader application of this model. Our results introduce a multi-species, two-tissue clock for broader applicability across cetaceans, alongside single-tissue multi-species clocks for blood and skin, which allow for more detailed aging analysis depending on the availability of samples. In addition, we developed species-specific clocks for enhanced precision, resulting in four blood-specific clocks and eight skin-specific clocks for individual species; all improving upon existing accuracy estimates for previously published species-specific clocks. By pooling methylation data from various studies, we increased our sample size, significantly enhancing the statistical power for building accurate clocks. These new epigenetic age estimators for cetaceans provide more accurate tools for aiding in conservation efforts of endangered cetaceans.

Age‐associated DNA‐methylation profiles have been used successfully to develop highly accurate biomarkers of age (\"epigenetic clocks\") in humans, mice, dogs, and other species. Here we present epigenetic clocks for African and Asian elephants. These clocks were developed using novel DNA methylation profiles of 140 elephant blood samples of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40). We present epigenetic clocks for Asian elephants (Elephas maximus), African elephants (Loxodonta africana), and both elephant species combined. Two additional human‐elephant clocks were constructed by combining human and elephant samples. Epigenome‐wide association studies identified elephant age‐related CpGs and their proximal genes. The products of these genes play important roles in cellular differentiation, organismal development, metabolism, and circadian rhythms. Intracellular events observed to change with age included the methylation of bivalent chromatin domains, and targets of polycomb repressive complexes. These readily available epigenetic clocks can be used for elephant conservation efforts where accurate estimates of age are needed to predict demographic trends. DNA methylation aging clocks for African and Asian elephants. Some of these clocks apply to humans as well. Parts of the graphic were created by Hollis Burbank‐Hammerlund, Sandra Oviedo, and BioRender.com.

Naked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we profiled n  = 385 samples from 11 tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). We observed strong epigenetic aging effects and developed seven highly accurate epigenetic clocks for several tissues (pan-tissue, blood, kidney, liver, skin clocks) and two dual-species (human–NMR) clocks. The skin clock correctly estimated induced pluripotent stem cells derived from NMR fibroblasts to be of prenatal age. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than nonbreeders, a feature that is also observed in some eusocial insects. Our results show that despite a phenotype of negligible senescence, the NMR ages epigenetically.

The quality of romantic relationships can predict health consequences related to aging. DNA methylation-based biomarkers of aging accurately estimate chronological age. We developed several highly accurate epigenetic aging clocks, based on highly conserved mammalian CpGs, for the socially monogamous prairie vole ( Microtus ochrogaster ). In addition, our dual-species human-vole clock accurately measured relative age and illustrates high species conservation of epigenetic aging effects. Next, we assessed how pair bonding impacts epigenetic aging. We did not find evidence that pair-bonded voles exhibit accelerated or decelerated epigenetic aging effects in blood, ear, liver, or brain tissue. Our epigenome wide association study identified CpGs in five genes strongly associated with pair bonding: Foxp4 , Phf2, Mms22l, Foxb1, and Eif1ad . Overall, we present accurate DNA methylation-based estimators of age for a species of great interest to researchers studying monogamy in animals. We did not find any evidence that sex-naive animals age differently from pair-bonded animals.

To address how conserved DNA methylation-based epigenetic aging is in diverse branches of the tree of life, we generated DNA methylation data from African clawed frogs ( Xenopus laevis ) and Western clawed frogs ( Xenopus tropicalis ) and built multiple epigenetic clocks. Dual species clocks were developed that apply to both humans and frogs (human-clawed frog clocks), supporting that epigenetic aging processes are evolutionary conserved outside mammals. Highly conserved positively age-related CpGs are located in neural-developmental genes such as uncx , tfap2d as well as nr4a2 implicated in age-associated disease. We conclude that signatures of epigenetic aging are evolutionary conserved between frogs and mammals and that the associated genes relate to neural processes, altogether opening opportunities to employ Xenopus as a model organism to study aging.

Knowledge of an animal's chronological age is crucial for understanding and predicting population demographics, survival and reproduction, but accurate age determination for many wild animals remains challenging. Previous methods to estimate age require invasive procedures, such as tooth extraction to analyse growth layers, which are difficult to carry out with large, mobile animals such as cetaceans. However, recent advances in epigenetic methods have opened new avenues for precise age determination. These ‘epigenetic clocks’ present a less invasive alternative and can provide age estimates with unprecedented accuracy. Here, we present a species‐specific epigenetic clock based on skin tissue samples for a population of Indo‐Pacific bottlenose dolphins (Tursiops aduncus) in Shark Bay, Western Australia. We measured methylation levels at 37,492 cytosine‐guanine sites (CpG sites) in 165 samples using the mammalian methylation array. Chronological age estimates with an accuracy of ±1 year were available for 68 animals as part of a long‐term behavioral study of this population. Using these samples with known age, we built an elastic net model with Leave‐One‐Out‐Cross‐Validation, which retained 43 CpG sites, providing an r = 0.86 and median absolute age error (MAE) = 2.1 years (5% of maximum age). This model was more accurate for our data than the previously published methylation clock based on skin samples of common bottlenose dolphins (T. truncatus: r = 0.83, MAE = 2.2) and the multi‐species odontocete methylation clock (r = 0.68, MAE = 6.8), highlighting that species‐specific clocks can have superior performance over those of multi‐species assemblages. We further developed an epigenetic sex estimator, predicting sex with 100% accuracy. As age and sex are critical parameters for the study of animal populations, this clock and sex estimator will provide a useful tool for extracting life history information from skin samples rather than long‐term observational data for free‐ranging Indo‐Pacific bottlenose dolphins worldwide.

Age determination of wild animals, including pinnipeds, is critical for accurate population assessment and management. For most pinnipeds, current age estimation methodologies utilize tooth or bone sectioning which makes antemortem estimations problematic. We leveraged recent advances in the development of epigenetic age estimators (epigenetic clocks) to develop highly accurate pinniped epigenetic clocks. For clock development, we applied the mammalian methylation array to profile 37,492 cytosine-guanine sites (CpGs) across highly conserved stretches of DNA in blood and skin samples ( n  = 171) from primarily three pinniped species representing the three phylogenetic families: Otariidae, Phocidae and Odobenidae. We built an elastic net model with Leave-One-Out-Cross Validation (LOOCV) and one with a Leave-One-Species-Out-Cross-Validation (LOSOCV). After identifying the top 30 CpGs, the LOOCV produced a highly correlated (r = 0.95) and accurate (median absolute error = 1.7 years) age estimation clock. The LOSOCV elastic net results indicated that blood and skin clock ( r  = 0.84) and blood ( r  = 0.88) pinniped clocks could predict age of animals from pinniped species not used for clock development to within 3.6 and 4.4 years, respectively. These epigenetic clocks provide an improved and relatively non-invasive tool to determine age in skin or blood samples from all pinniped species. DNA methylation aging clocks are generated for several species of pinnipeds enabling the estimation of pinniped age from blood or skin samples.