scholarly journals Pseudotime analysis reveals exponential trends in DNA methylation aging with mortality associated timescales

2021 ◽  
Author(s):  
Kalsuda Lapborisuth ◽  
Colin Farrell ◽  
Matteo Pellegrini
Keyword(s):  
Dna Methylation ◽  
Brain Tissue ◽  
Human Blood ◽  
Mortality Risk ◽  
Functional Form ◽  
Nonlinear Relationship ◽  
Rapid Changes ◽  
Highly Correlated ◽  
Latent Dimension ◽  
First Time

The epigenetic trajectory of DNA methylation profiles has a nonlinear relationship with time, reflecting rapid changes in DNA methylation early in life that progressively slow. In this study, we use pseudotime analysis to determine these trajectories. Unlike epigenetic clocks that constrain the functional form of methylation changes with time, pseudotime analysis orders samples along a path based on similarities in a latent dimension to provide an unbiased trajectory. We show that pseudotime analysis can be applied to DNA methylation in human blood and brain tissue and find that it is highly correlated with the epigenetic states described by the Epigenetic Pacemaker. Moreover, we show that the pseudotime nonlinear trajectory can be modeled using a sum of two exponentials with coefficients that are close to the timescales of human age-associated mortality. Thus, for the first time, we can identify age-associated molecular changes that appear to track the exponential dynamics of mortality risk.

Adhesion and Growth of Anaerobic Biofilms on Ion Exchange Resins

1986 ◽  
Vol 21 (4) ◽  
pp. 486-495 ◽  
Author(s):  
R.F.G. Selle Sardi ◽  
W. Bulani ◽  
W.L. Cairns ◽  
N. Kosaric
Keyword(s):  
Metabolic Activity ◽  
Cation Binding ◽  
Fatty Acid Substrate ◽  
Anaerobic Reactors ◽  
Initial Adhesion ◽  
Rapid Changes ◽  
Exchange Resins ◽  
Biofilm Development ◽  
First Time ◽  
Acid Substrate

Abstract Ion exchanger beads are explored as aids in accelerating the development of anaerobic biofilms for use in advanced anaerobic reactors. Initial adhesion and subsequent changes in adhesion and growth of anaerobic biofilms (as reflected in total supported biomass and metabolic activity) were monitored on different ion exchangers (strong cation, strong anion and weak anion) over a period of 12 days. Metabolic activity was recorded for the first time in this type of study using ATP biolumininescence assays which allowed monitoring of rapid changes in the biofilm development. Results indicate that the strong cation exchanger is a better overall substratum for anaerobic biofilm development due to its favorable property of dialent cation binding and adsorption of volatile fatty acid substrate for methanogens.

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

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Todd R. Robeck ◽  
Zhe Fei ◽  
Ake T. Lu ◽  
Amin Haghani ◽  
Eve Jourdain ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Age Estimation ◽  
Species Conservation ◽  
Genome Wide ◽  
Epigenetic Aging ◽  
Highly Correlated ◽  
Methylation Patterns ◽  
Cg Dinucleotides ◽  
Free Ranging ◽  
Unique Species

AbstractThe 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.

scholarly journals Differential DNA Methylation in Purified Human Blood Cells: Implications for Cell Lineage and Studies on Disease Susceptibility

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41361 ◽  
Author(s):  
Lovisa E. Reinius ◽  
Nathalie Acevedo ◽  
Maaike Joerink ◽  
Göran Pershagen ◽  
Sven-Erik Dahlén ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Blood ◽  
Blood Cells ◽  
Disease Susceptibility ◽  
Cell Lineage ◽  
Human Blood Cells

Associations of DNA Methylation Mortality Risk Markers with Congenital Microcephaly from Zika Virus: A Study of Brazilian Children Less than 4 Years of Age

2021 ◽  
Vol 67 (1) ◽  
Author(s):  
Jamaji C Nwanaji-Enwerem ◽  
Lars Van Der Laan ◽  
Elorm F Avakame ◽  
Kristan A Scott ◽  
Heather H Burris ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mortality Risk ◽  
Zika Virus ◽  
Clinical Decision Making ◽  
Linear Models ◽  
Adult Mortality ◽  
Plasminogen Activator Inhibitor 1 ◽  
Congenital Microcephaly ◽  
Pai 1 ◽  
Brazilian Children

ABSTRACT Background Zika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust pediatric mortality risk metrics are needed to help guide life plans and clinical decision making for these patients. Although common etiologies of pediatric and adult mortality differ, early life health can impact adult outcomes—potentially through DNA methylation. Hence, in this pilot study, we take an early step in identifying pediatric mortality risk metrics by examining associations of ZIKV infection and associated congenital microcephaly with existing adult DNA methylation-based mortality biomarkers: GrimAge and Zhang’s mortality score (ZMS). Methods Mortality measures were calculated from previously published HumanMethylationEPIC BeadChip data from 44 Brazilian children aged 5–40 months (18 with ZIKV-associated microcephaly; 7 normocephalic, exposed to ZIKV in utero; and 19 unexposed controls). We used linear models adjusted for chronological age, sex, methylation batch and white blood cell proportions to evaluate ZIKV and mortality marker relationships. Results We observed significant decreases in GrimAge-component plasminogen activator inhibitor-1 [PAI-1; β = −2453.06 pg/ml, 95% confidence interval (CI) −3652.96, −1253.16, p = 0.0002], and ZMS-site cg14975410 methylation (β = −0.06, 95% CI −0.09, −0.03, p = 0.0003) among children with microcephaly compared to controls. PAI-1 (β = −2448.70 pg/ml, 95% CI −4384.45, −512.95, p = 0.01) and cg14975410 (β = 0.01, 95% CI −0.04, 0.06, p = 0.64) results in comparisons of normocephalic, ZIKV-exposed children to controls were not statistically significant. Conclusion Our results suggest that elements of previously-identified adult epigenetic markers of mortality risk are associated with ZIKV-associated microcephaly, a known contributor to pediatric mortality risk. These findings may provide insights for efforts aimed at developing pediatric mortality markers.

scholarly journals No cell is an island: circulating T cell:monocyte complexes are markers of immune perturbations

2018 ◽  
Author(s):  
Julie G. Burel ◽  
Mikhail Pomaznoy ◽  
Cecilia S. Lindestam Arlehamn ◽  
Daniela Weiskopf ◽  
Ricardo da Silva Antunes ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Immune Responses ◽  
Human Blood ◽  
Significant Proportion ◽  
Complex Frequency ◽  
The Common ◽  
First Time ◽  
High Resolution Microscopy

AbstractOur results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artefacts and thus ignored in data acquisition and analysis, are the result of true biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell:monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be revisited.

scholarly journals To Determine Pivotal Genes Driven by Methylated DNA in Obstructive Sleep Apnea Hypopnea Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yan Li ◽  
Yajuan Zhang
Keyword(s):  
Dna Methylation ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Molecular Mechanisms ◽  
Sleep Apnea Syndrome ◽  
Respiratory Dysfunction ◽  
Obstructive Sleep ◽  
Hypopnea Syndrome ◽  
First Time ◽  
Erbb2 Signaling

Obstructive sleep apnea syndrome (OSAHS) is a widespread respiratory dysfunction that has attracted more and more attention in recent years. Recently, a large number of studies have shown that abnormal DNA methylation epigenetically silences genes necessary for the pathogenesis of human diseases. However, the exact mechanism of abnormal DNA methylation in OSAHS is still elusive. In this study, we downloaded the OSAHS data from the GEO database. Our data for the first time revealed 520 hypermethylated genes and 889 hypomethylated genes in OSAHS. Bioinformatics analysis revealed that these abnormal methylated genes exhibited an association with the regulation of angiogenesis, apoptosis, Wnt, and ERBB2 signaling pathways. PPI network analysis displayed the interactions among these genes and validated several hub genes, such as GPSM2, CCR8, TAS2R20, TAS2R4, and TAS2R5, which were related to regulating liganded Gi-activating GPCR and the transition of mitotic metaphase/anaphase. In conclusion, our study offers a new hint of understanding the molecular mechanisms in OSAHS progression and will provide OSAHS with newly generated innovative biomarkers.

scholarly journals Validation and characterization of a DNA methylation alcohol biomarker across the life course

2019 ◽  
Author(s):  
Paul Darius Yousefi ◽  
Rebecca Richmond ◽  
Ryan Langdon ◽  
Andrew Ness ◽  
Chunyu Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Parents And Children ◽  
Average Alcohol ◽  
Alcohol Biomarker ◽  
Audit Score ◽  
Potential Applications ◽  
The Life Course ◽  
Offspring Generation ◽  
First Time

AbstractRecently, an alcohol predictor was developed using DNA methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health. We validate the performance and characterize the drivers of this DNAm-Alc for the first time in independent populations. In N=1,049 parents from the Avon Longitudinal Study of Parents and Children (ALSPAC) Accessible Resource for Integrated Epigenomic Studies (ARIES) at midlife, we found DNAm-Alc explained 7.6% of the variation in alcohol intake, roughly half of what had been reported previously, and interestingly explained a larger 9.8% of AUDIT score, a scale of alcohol use disorder. Explanatory capacity in participants from the offspring generation of ARIES measured during adolescence was much lower. However, DNAm-Alc explained 14.3% of the variation in replication using the Head and Neck 5000 (HN5000) clinical cohort that had higher average alcohol consumption. To investigate whether this relationship was being driven by genetic and/or earlier environment confounding we examined how earlier vs. concurrent DNAm-Alc measures predicted AUDIT scores. In both ARIES parental and offspring generations, we observed associations between AUDIT and concurrent, but not earlier DNAm-Alc, suggesting independence from genetic and stable environmental contributions. The stronger relationship between DNAm-Alcs and AUDIT in parents at midlife compared to adolescents despite similar levels of consumption suggests that DNAm-Alc likely reflects long-term patterns of alcohol abuse. Such biomarkers may have potential applications for biomonitoring and risk prediction, especially in cases where reporting bias is a concern.

Search for Pharmacoepigenetic Correlations in Type 2 Diabetes Under Sulfonylurea Treatment

2018 ◽  
Vol 127 (04) ◽  
pp. 226-233 ◽  
Author(s):  
Makrina Karaglani ◽  
Georgia Ragia ◽  
Maria Panagopoulou ◽  
Ioanna Balgkouranidou ◽  
Evangelia Nena ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Promoter ◽  
Katp Channels ◽  
Protective Role ◽  
Gene Promoters ◽  
Specific Pcr ◽  
Abcc8 Gene ◽  
First Time ◽  
E23k Polymorphism

AbstractSulfonylureas are insulin secretagogues which act in pancreatic β cells by blocking the KATP channels encoded by KCNJ11 and ABCC8 genes. In the present study, a pharmacoepigenetic approach was applied for the first time, investigating the correlation of KCNJ11 and ABCC8 gene promoter methylation with sulfonylureas-induced mild hypoglycemic events as well as the KCNJ11 E23K genotype. Sodium bisulfite-treated genomic DNA of 171 sulfonylureas treated T2DM patients previously genotyped for KCNJ11 E23K, including 88 that had experienced drug-associated hypoglycemia and 83 that had never experienced hypoglycemia, were analyzed for DNA methylation of KCNJ11 and ABCC8 gene promoters via quantitative Methylation-Specific PCR. KCNJ11 methylation was detected in 19/88 (21.6%) of hypoglycemic and in 23/83 (27.7%) of non-hypoglycemic patients (p=0.353), while ABCC8 methylation in 6/83 (7.2%) of non-hypoglycemic and none (0/88) of the hypoglycemic patients (p=0.012). Methylation in at least one promoter (KCNJ11 or ABCC8) was significantly associated with non-hypoglycemic patients who are carriers of KCNJ11 EK allele (p=0.030). Our data suggest that ABCC8 but not KCNJ11 methylation is associated to hypoglycemic events in sulfonylureas-treated T2DM patients. Furthermore, it is demonstrated that the KCNJ11 E23K polymorphism in association to either of the two genes’ DNA methylation may have protective role against sulfonylurea-induced hypoglycemia.

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