Epigenetic age oscillates during the day.

Since their introduction, epigenetic clocks have been extensively used in aging, human disease, and rejuvenation studies. In this article, we report an intriguing pattern: epigenetic age predictions display a 24-h periodicity. We tested a circadian blood sample collection using 17 epigenetic clocks addressing different aspects of aging.

Diurnal oscillations of MRI metrics in the brains of male participants.

Regulation of biological processes according to a 24-hr rhythm is essential for the normal functioning of an organism. Temporal variation in brain MRI data has often been attributed to circadian or diurnal oscillations; however, it is not clear if such oscillations exist. Here, we provide evidence that diurnal oscillations indeed govern multiple MRI metrics.

Scikick: A sidekick for workflow clarity and reproducibility during extensive data analysis.

Reproducibility is crucial for scientific progress, yet a clear research data analysis workflow is challenging to implement and maintain. As a result, a record of computational steps performed on the data to arrive at the key research findings is often missing. We developed Scikick, a tool that eases the configuration, execution, and presentation of scientific computational analyses.

Deep Q-Learning in Robotics: Improvement of Accuracy and Repeatability.

Recent industrial robotics covers a broad part of the manufacturing spectrum and other human everyday life applications; the performance of these devices has become increasingly important. Positioning accuracy and repeatability, as well as operating speed, are essential in any industrial robotics application. Robot positioning errors are complex due to the extensive combination of their sources and cannot be compensated for using conventional methods.

Origins of human disease: the chrono-epigenetic perspective.

Epigenetics has enriched human disease studies by adding new interpretations to disease features that cannot be explained by genetic and environmental factors. However, identifying causal mechanisms of epigenetic origin has been challenging. New opportunities have risen from recent findings in intra-individual and cyclical epigenetic variation, which includes circadian epigenetic oscillations.

DiscoRhythm: an easy-to-use web application and R package for discovering rhythmicity.

Motivation: Biological rhythmicity is fundamental to almost all organisms on Earth and plays a key role in health and disease. Identification of oscillating signals could lead to novel biological insights, yet its investigation is impeded by the extensive computational and statistical knowledge required to perform such analysis.

Results: To address this issue, we present DiscoRhythm (Discovering Rhythmicity), a user-friendly application for characterizing rhythmicity in temporal biological data.

Epigenetic dysregulation of enhancers in neurons is associated with Alzheimer's disease pathology and cognitive symptoms.

Epigenetic control of enhancers alters neuronal functions and may be involved in Alzheimer's disease (AD). Here, we identify enhancers in neurons contributing to AD by comprehensive fine-mapping of DNA methylation at enhancers, genome-wide. We examine 1.

Differential methylation of enhancer at IGF2 is associated with abnormal dopamine synthesis in major psychosis.

Impaired neuronal processes, including dopamine imbalance, are central to the pathogenesis of major psychosis, but the molecular origins are unclear. Here we perform a multi-omics study of neurons isolated from the prefrontal cortex in schizophrenia and bipolar disorder (n = 55 cases and 27 controls). DNA methylation, transcriptomic, and genetic-epigenetic interactions in major psychosis converged on pathways of neurodevelopment, synaptic activity, and immune functions.

Circadian oscillations of cytosine modification in humans contribute to epigenetic variability, aging, and complex disease.

Background: Maintenance of physiological circadian rhythm plays a crucial role in human health. Numerous studies have shown that disruption of circadian rhythm may increase risk for malignant, psychiatric, metabolic, and other diseases.

Results: Extending our recent findings of oscillating cytosine modifications (osc-modCs) in mice, in this study, we show that osc-modCs are also prevalent in human neutrophils.

Cell-Free DNA Modification Dynamics in Abiraterone Acetate-Treated Prostate Cancer Patients.

Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20% to 40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance. We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients.

Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging.

Circadian rhythmicity governs a remarkable array of fundamental biological functions and is mediated by cyclical transcriptomic and proteomic activities. Epigenetic factors are also involved in this circadian machinery; however, despite extensive efforts, detection and characterization of circadian cytosine modifications at the nucleotide level have remained elusive. In this study, we report that a large proportion of epigenetically variable cytosines show a circadian pattern in their modification status in mice.

Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice.

Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted.

Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome.

Transcriptional variation in histologically- and genetically- identical cells is a widespread phenomenon in tissues, yet the processes conferring this heterogeneity are not well understood. To identify contributing factors, we analyzed epigenetic profiles associated with the in vivo transcriptional gradient of the mouse lactase gene (Lct), which occurs in enterocytes along the proximal-to-distal axis of the small intestine. We found that epigenetic signatures at enhancer and promoter elements aligns with transcriptional variation of Lct in enterocytes.

Lactase nonpersistence is directed by DNA-variation-dependent epigenetic aging.

The inability to digest lactose, due to lactase nonpersistence, is a common trait in adult mammals, except in certain human populations that exhibit lactase persistence. It is not known how the lactase gene is dramatically downregulated with age in most individuals but remains active in some individuals. We performed a comprehensive epigenetic study of human and mouse small intestines, by using chromosome-wide DNA-modification profiling and targeted bisulfite sequencing.

Epigenetic assimilation in the aging human brain.

Background: Epigenetic drift progressively increases variation in DNA modification profiles of aging cells, but the finale of such divergence remains elusive. In this study, we explored the dynamics of DNA modification and transcription in the later stages of human life.

Results: We find that brain tissues of older individuals (>75 years) become more similar to each other, both epigenetically and transcriptionally, compared with younger individuals.

Allele-Skewed DNA Modification in the Brain: Relevance to a Schizophrenia GWAS.

Numerous recent studies have suggested that phenotypic effects of DNA sequence variants can be mediated or modulated by their epigenetic marks, such as allele-skewed DNA modification (ASM). Using Affymetrix SNP microarrays, we performed a comprehensive search of ASM effects in human post-mortem brain and sperm samples (total n = 256) from individuals with major psychosis and control individuals. Depending on the phenotypic category of the brain samples, 1.

High Precision DNA Modification Analysis of HCG9 in Major Psychosis.

New epigenetic technologies may uncover etiopathogenic mechanisms of major psychosis. In this study, we applied padlock probe-based ultra-deep bisulfite sequencing for fine mapping of modified cytosines of the HLA complex group 9 (nonprotein coding) gene in the postmortem brains of individuals affected with schizophrenia or bipolar disorder and unaffected controls. Significant differences between patients and controls were detected in both CpG and CpH modifications.

Further Evidence Supporting a Parent-of-Origin Effect in Psoriatic Disease.

Objective: To further explore the "parent-of-origin" effect in a large cohort of well-phenotyped patients with cutaneous psoriasis without arthritis (PsC) and psoriatic arthritis (PsA).

Methods: Self-reported family history was obtained from PsA patients from Toronto and Newfoundland satisfying the Classification of Psoriatic Arthritis criteria, and PsC patients from Toronto, who were examined by a rheumatologist to exclude PsA. Proportions of probands with paternally and maternally transmitted psoriatic disease were compared by McNemar's and chi-square tests.

DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.

Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined.

Methods: We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.

DNA unmethylome profiling by covalent capture of CpG sites.

Dynamic patterns of cytosine-5 methylation and successive hydroxylation are part of epigenetic regulation in eukaryotes, including humans, which contributes to normal phenotypic variation and disease risk. Here we present an approach for the mapping of unmodified regions of the genome, which we call the unmethylome. Our technique is based on DNA methyltransferase-directed transfer of activated groups and covalent biotin tagging of unmodified CpG sites followed by affinity enrichment and interrogation on tiling microarrays or next generation sequencing.

Validating reference genes within a mouse model system of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity.

Background: Quantitative real-time PCR (qPCR) is the "gold-standard" technique for measuring mRNA abundances. To correctly compare samples and generate biologically valid results, qPCR data usually require comprehensive normalization to account for sample content variation between reactions. The most common normalization approaches use one or more endogenous controls (reference or house-keeping genes) to adjust the measured levels of experimental genes appropriately.

Quantitative leukocyte BDNF promoter methylation analysis in bipolar disorder.

Background: Bipolar disorder (BD) is a complex psychiatric phenotype with a high heritability and a multifactorial etiology. Multisite collaborative efforts using genome-wide association studies (GWAS) have identified only a portion of DNA sequence-based risk factors in BD. In addition to predisposing DNA sequence variants, epigenetic misregulation may play an etiological role in BD and account for monozygotic twin discordance, parental origin effects, and fluctuating course of BD.