Publications by authors named "Joseph A Zoller"

6 Publications

  • Page 1 of 1

Epigenetic clock and methylation studies in elephants.

Aging Cell 2021 Jul 12;20(7):e13414. Epub 2021 Jun 12.

Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.

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.
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http://dx.doi.org/10.1111/acel.13414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282242PMC
July 2021

Multi-species and multi-tissue methylation clocks for age estimation in toothed whales and dolphins.

Commun Biol 2021 05 31;4(1):642. Epub 2021 May 31.

Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.

The development of a precise blood or skin tissue DNA Epigenetic Aging Clock for Odontocete (OEAC) would solve current age estimation inaccuracies for wild odontocetes. Therefore, we determined genome-wide DNA methylation profiles using a custom array (HorvathMammalMethyl40) across skin and blood samples (n = 446) from known age animals representing nine odontocete species within 4 phylogenetic families to identify age associated CG dinucleotides (CpGs). The top CpGs were used to create a cross-validated OEAC clock which was highly correlated for individuals (r = 0.94) and for unique species (median r = 0.93). Finally, we applied the OEAC for estimating the age and sex of 22 wild Norwegian killer whales. DNA methylation patterns of age associated CpGs are highly conserved across odontocetes. These similarities allowed us to develop an odontocete epigenetic aging clock (OEAC) which can be used for species conservation efforts by provide a mechanism for estimating the age of free ranging odontocetes from either blood or skin samples.
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http://dx.doi.org/10.1038/s42003-021-02179-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167141PMC
May 2021

Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging.

Aging Cell 2021 05 2;20(5):e13349. Epub 2021 Apr 2.

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Cattle are an attractive animal model of fertility in women due to their high degree of similarity relative to follicle selection, embryo cleavage, blastocyst formation, and gestation length. To facilitate future studies of the epigenetic underpinnings of aging effects in the female reproductive axis, several DNA methylation-based biomarkers of aging (epigenetic clocks) for bovine oocytes are presented. One such clock was germane to only oocytes, while a dual-tissue clock was highly predictive of age in both oocytes and blood. Dual species clocks that apply to both humans and cattle were also developed and evaluated. These epigenetic clocks can be used to accurately estimate the biological age of oocytes. Both epigenetic clock studies and epigenome-wide association studies revealed that blood and oocytes differ substantially with respect to aging and the underlying epigenetic signatures that potentially influence the aging process. The rate of epigenetic aging was found to be slower in oocytes compared to blood; however, oocytes appeared to begin at an older epigenetic age. The epigenetic clocks for oocytes are expected to address questions in the field of reproductive aging, including the central question: how to slow aging of oocytes.
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http://dx.doi.org/10.1111/acel.13349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135012PMC
May 2021

Pandemic velocity: Forecasting COVID-19 in the US with a machine learning & Bayesian time series compartmental model.

PLoS Comput Biol 2021 03 29;17(3):e1008837. Epub 2021 Mar 29.

Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, California, United States of America.

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.
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http://dx.doi.org/10.1371/journal.pcbi.1008837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031749PMC
March 2021

Pseudo-likelihood based logistic regression for estimating COVID-19 infection and case fatality rates by gender, race, and age in California.

Epidemics 2020 12 9;33:100418. Epub 2020 Nov 9.

Department of Biostatistics, Jonathan and Karen Fielding School of Public Health, University of California, Los Angeles, CA, United States of America. Electronic address:

In emerging epidemics, early estimates of key epidemiological characteristics of the disease are critical for guiding public policy. In particular, identifying high-risk population subgroups aids policymakers and health officials in combating the epidemic. This has been challenging during the coronavirus disease 2019 (COVID-19) pandemic because governmental agencies typically release aggregate COVID-19 data as summary statistics of patient demographics. These data may identify disparities in COVID-19 outcomes between broad population subgroups, but do not provide comparisons between more granular population subgroups defined by combinations of multiple demographics. We introduce a method that helps to overcome the limitations of aggregated summary statistics and yields estimates of COVID-19 infection and case fatality rates - key quantities for guiding public policy related to the control and prevention of COVID-19 - for population subgroups across combinations of demographic characteristics. Our approach uses pseudo-likelihood based logistic regression to combine aggregate COVID-19 case and fatality data with population-level demographic survey data to estimate infection and case fatality rates for population subgroups across combinations of demographic characteristics. We illustrate our method on California COVID-19 data to estimate test-based infection and case fatality rates for population subgroups defined by gender, age, and race/ethnicity. Our analysis indicates that in California, males have higher test-based infection rates and test-based case fatality rates across age and race/ethnicity groups, with the gender gap widening with increasing age. Although elderly infected with COVID-19 are at an elevated risk of mortality, the test-based infection rates do not increase monotonically with age. The workforce population, especially, has a higher test-based infection rate than children, adolescents, and other elderly people in their 60-80. LatinX and African Americans have higher test-based infection rates than other race/ethnicity groups. The subgroups with the highest 5 test-based case fatality rates are all-male groups with race as African American, Asian, Multi-race, LatinX, and White, followed by African American females, indicating that African Americans are an especially vulnerable California subpopulation.
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http://dx.doi.org/10.1016/j.epidem.2020.100418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837024PMC
December 2020

Enhancer Chromatin and 3D Genome Architecture Changes from Naive to Primed Human Embryonic Stem Cell States.

Stem Cell Reports 2019 05 2;12(5):1129-1144. Epub 2019 May 2.

Division of Medical Genetics, Department of Medicine, Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, USA. Electronic address:

During mammalian embryogenesis, changes in morphology and gene expression are concurrent with epigenomic reprogramming. Using human embryonic stem cells representing the preimplantation blastocyst (naive) and postimplantation epiblast (primed), our data in 2iL/I/F naive cells demonstrate that a substantial portion of known human enhancers are premarked by H3K4me1, providing an enhanced open chromatin state in naive pluripotency. The 2iL/I/F enhancer repertoire occupies 9% of the genome, three times that of primed cells, and can exist in broad chromatin domains over 50 kb. Enhancer chromatin states are largely poised. Seventy-seven percent of 2iL/I/F enhancers are decommissioned in a stepwise manner as cells become primed. While primed topologically associating domains are largely unaltered upon differentiation, naive 2iL/I/F domains expand across primed boundaries, affecting three-dimensional genome architecture. Differential topologically associating domain edges coincide with 2iL/I/F H3K4me1 enrichment. Our results suggest that naive-derived 2iL/I/F cells have a unique chromatin landscape, which may reflect early embryogenesis.
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http://dx.doi.org/10.1016/j.stemcr.2019.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524944PMC
May 2019
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